Role of tyrosine kinase Jak2 in prolactin-induced differentiation and growth of mammary epithelial cells.
AuthorsXie Jianwu; LeBaron Matthew J; Nevalainen Marja T; Rui Hallgeir;
JournalJ Biol Chem
PubMed ID11821424
Genetic studies in mice have established a critical role for prolactin receptors and transcription factor Stat5 in mammary gland differentiation. However, the enzymatic coupling between prolactin receptors and Stat5 in this process has not been established. In addition to Jak2, several other tyrosine kinases reportedly also are associated with prolactin ... More
Confirmation by FRET in individual living cells of the absence of significant amyloid beta -mediated caspase 8 activation.
When cells are exposed to death-inducing molecules such as tumor necrosis factor-alpha or Fas, caspase 8 is activated and cleaves an apoptotic facilitator, Bid, that is a member of the Bcl-2 family. After additional modification, the C-terminal moiety of Bid is translocated to the mitochondria and induces the release of ... More
AMP-activated Kinase Inhibits the Epithelial Na+ Channel through Functional Regulation of the Ubiquitin Ligase Nedd4-2.
'We recently found that the metabolic sensor AMP-activated kinase (AMPK) inhibits the epithelial Na(+) channel (ENaC) through decreased plasma membrane ENaC expression, an effect requiring the presence of a binding motif in the cytoplasmic tail of the beta-ENaC subunit for the ubiquitin ligase Nedd4-2. To further examine the role of ... More
Mammalian cell penetration, siRNA transfection, and DNA transfection by supercharged proteins.
AuthorsMcNaughton BR, Cronican JJ, Thompson DB, Liu DR,
JournalProc Natl Acad Sci U S A
PubMed ID19307578
'Nucleic acid reagents, including small interfering RNA (siRNA) and plasmid DNA, are important tools for the study of mammalian cells and are promising starting points for the development of new therapeutic agents. Realizing their full potential, however, requires nucleic acid delivery reagents that are simple to prepare, effective across many ... More
Dynamic fluorescent imaging of human immunodeficiency virus type 1 gag in live cells by biarsenical labeling.
AuthorsRudner L, Nydegger S, Coren LV, Nagashima K, Thali M, Ott DE,
JournalJ Virol
PubMed ID15767407
'Human immunodeficiency virus type 1 (HIV-1) Gag is the primary structural protein of the virus and is sufficient for particle formation. We utilized the recently developed biarsenical-labeling method to dynamically observe HIV-1 Gag within live cells by adding a tetracysteine tag (C-C-P-G-C-C) to the C terminus of Gag in both ... More
Identification of a matrix-binding domain in MAGP1 and MAGP2 and intracellular localization of alternative splice forms.
Authors Segade Fernando; Trask Barbara Crippes; Broekelmann Thomas J; Pierce Richard A; Mecham Robert P;
JournalJ Biol Chem
PubMed ID11796718
'MAGP1 is a small molecular mass protein associated with microfibrils in the extracellular matrix (ECM). To identify the molecular basis of its interaction with other microfibrillar proteins, deletion constructs of MAGP1 were expressed in a mammalian cell system that served as a model for microfibril assembly. This study identified a ... More
Amino acid residues critical for endoplasmic reticulum export and trafficking of platelet-activating factor receptor.
AuthorsHirota N, Yasuda D, Hashidate T, Yamamoto T, Yamaguchi S, Nagamune T, Nagase T, Shimizu T, Nakamura M,
JournalJ Biol Chem
PubMed ID20007715
'Several residues are conserved in the transmembrane domains (TMs) of G-protein coupled receptors. Here we demonstrate that a conserved proline, Pro(247), in TM6 of platelet-activating factor receptor (PAFR) is required for endoplasmic reticulum (ER) export and trafficking after agonist-induced internalization. Alanine-substituted mutants of the conserved residues of PAFRs, including P247A, ... More
Rrn3 phosphorylation is a regulatory checkpoint for ribosome biogenesis.
Authors Cavanaugh Alice H; Hirschler-Laszkiewicz Iwona; Hu Qiyue; Dundr Miroslav; Smink Tom; Misteli Tom; Rothblum Lawrence I;
JournalJ Biol Chem
PubMed ID12015311
'Cycloheximide inhibits ribosomal DNA (rDNA) transcription in vivo. The mouse homologue of yeast Rrn3, a polymerase-associated transcription initiation factor, can complement extracts from cycloheximide-treated mammalian cells. Cycloheximide inhibits the phosphorylation of Rrn3 and causes its dissociation from RNA polymerase I. Rrn3 interacts with the rpa43 subunit of RNA polymerase I, ... More
Akt-dependent Phosphorylation of p27Kip1 Promotes Binding to 14-3-3 and Cytoplasmic Localization.
Authors Fujita Naoya; Sato Saori; Katayama Kazuhiro; Tsuruo Takashi;
JournalJ Biol Chem
PubMed ID12042314
'In many human cancers, the cyclin-dependent kinase inhibitor p27(Kip1) is expressed at low or undetectable levels. The decreased p27(Kip1) expression allows cyclin-dependent kinase activity to cause cells to enter into S phase and correlates with poor patient survival. Inhibition of serine/threonine kinase Akt signaling by some pharmacological agents or by ... More
Furin-mediated processing of Pro-C-type natriuretic peptide.
AuthorsWu C, Wu F, Pan J, Morser J, Wu Q,
JournalJ Biol Chem
PubMed ID12736257
'C-type natriuretic peptide (CNP) is a member of the natriuretic peptide family that is involved in a variety of homeostatic processes. Here we characterize the processing essential for the conversion of the precursor, human pro-CNP, to the biologically active hormone. In human embryonic kidney 293 and chondrosarcoma SW 1353 cells, ... More
Caveolin regulates endocytosis of the muscle repair protein, dysferlin.
AuthorsHernández-Deviez DJ, Howes MT, Laval SH, Bushby K, Hancock JF, Parton RG,
JournalJ Biol Chem
PubMed ID18096699
'Dysferlin and Caveolin-3 are plasma membrane proteins associated with muscular dystrophy. Patients with mutations in the CAV3 gene show dysferlin mislocalization in muscle cells. By utilizing caveolin-null cells, expression of caveolin mutants, and different mutants of dysferlin, we have dissected the site of action of caveolin with respect to dysferlin ... More
Functional analysis of FSP27 protein regions for lipid droplet localization, caspase-dependent apoptosis, and dimerization with CIDEA.
AuthorsLiu K, Zhou S, Kim JY, Tillison K, Majors D, Rearick D, Lee JH, Fernandez-Boyanapalli RF, Barricklow K, Houston MS, Smas CM,
JournalAm J Physiol Endocrinol Metab
PubMed ID19843876
'The adipocyte-specific protein FSP27, also known as CIDEC, is one of three cell death-inducing DFF45-like effector (CIDE) proteins. The first known function for CIDEs was promotion of apoptosis upon ectopic expression in mammalian cells. Recent studies in endogenous settings demonstrated key roles for CIDEs in energy metabolism. FSP27 is a ... More
Loss of PINK1 function promotes mitophagy through effects on oxidative stress and mitochondrial fission.
AuthorsDagda RK, Cherra SJ, Kulich SM, Tandon A, Park D, Chu CT,
JournalJ Biol Chem
PubMed ID19279012
'Mitochondrial dysregulation is strongly implicated in Parkinson disease. Mutations in PTEN-induced kinase 1 (PINK1) are associated with familial parkinsonism and neuropsychiatric disorders. Although overexpressed PINK1 is neuroprotective, less is known about neuronal responses to loss of PINK1 function. We found that stable knockdown of PINK1 induced mitochondrial fragmentation and autophagy ... More
IQGAP1 Is a Component of Cdc42 Signaling to the Cytoskeleton.
Authors Swart-Mataraza Jennifer M; Li Zhigang; Sacks David B;
JournalJ Biol Chem
PubMed ID11948177
'The Ras-GAP related protein IQGAP1 binds several proteins, including actin, calmodulin, E-cadherin and the Rho family GTPase Cdc42. To gain insight into its in vivo function, IQGAP1 was overexpressed in mammalian cells. Transfection of IQGAP1 significantly increased the levels of active, GTP-bound Cdc42, resulting in the formation of peripheral actin ... More
Real-time visualization of HIV-1 GAG trafficking in infected macrophages.
AuthorsGousset K, Ablan SD, Coren LV, Ono A, Soheilian F, Nagashima K, Ott DE, Freed EO,
JournalPLoS Pathog
PubMed ID18369466
'HIV-1 particle production is driven by the Gag precursor protein Pr55(Gag). Despite significant progress in defining both the viral and cellular determinants of HIV-1 assembly and release, the trafficking pathway used by Gag to reach its site of assembly in the infected cell remains to be elucidated. The Gag trafficking ... More
Thiazolides, a new class of anti-influenza molecules targeting viral hemagglutinin at the post-translational level.
AuthorsRossignol JF, La Frazia S, Chiappa L, Ciucci A, Santoro MG,
JournalJ Biol Chem
PubMed ID19638339
'The emergence of highly contagious influenza A virus strains, such as the new H1N1 swine influenza, represents a serious threat to global human health. Efforts to control emerging influenza strains focus on surveillance and early diagnosis, as well as development of effective vaccines and novel antiviral drugs. Herein we document ... More
Requirement of helix 1 and the AF-2 domain of the thyroid hormone receptor for coactivation by PGC-1.
Authors Wu Yifei; Delerive Philippe; Chin William W; Burris Thomas P;
JournalJ Biol Chem
PubMed ID11751919
'Although PGC-1 (peroxisome proliferator-activated receptor-gamma coactivator-1) has been previously shown to enhance thyroid hormone receptor (TR)/retinoid X receptor-mediated ucp-1 gene expression in a ligand-induced manner in rat fibroblast cells, the precise mechanism of PGC-1 modulation of TR function has yet to be determined. In this study, we show that PGC-1 ... More
Fanconi anemia protein, FANCA, associates with BRG1, a component of the human SWI/SNF complex.
Authors Otsuki T; Furukawa Y; Ikeda K; Endo H; Yamashita T; Shinohara A; Iwamatsu A; Ozawa K; Liu J M;
JournalHum Mol Genet
PubMed ID11726552
'Fanconi anemia (FA) is a genetic disorder that predisposes to hematopoietic failure, birth defects and cancer. We identified an interaction between the FA protein, FANCA and brm-related gene 1 (BRG1) product. BRG1 is a subunit of the SWI/SNF complex, which remodels chromatin structure through a DNA-dependent ATPase activity. FANCA was ... More
Epithelial membrane proteins induce membrane blebbing and interact with the P2X7 receptor C terminus.
Authors Wilson Heather L; Wilson Stuart A; Surprenant Annmarie; North R Alan;
JournalJ Biol Chem
PubMed ID12107182
'The binding of extracellular ATP to the P2X(7) receptor opens an integral cation-permeable channel; it also leads to membrane blebbing and, in certain immune cells, interleukin-1beta secretion and eventual death. The latter three effects are unique to the P2X(7) receptor; also unique among P2X receptors is the long intracellular C ... More
Requirement of p53 targets in chemosensitization of colonic carcinoma to death ligand therapy.
AuthorsWang S, El-Deiry WS,
JournalProc Natl Acad Sci U S A
PubMed ID14645705
'Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exhibits specific tumoricidal activity and is under development for cancer therapy. Mismatch-repair-deficient colonic tumors evade TRAIL-induced apoptosis through mutational inactivation of Bax, but chemotherapeutics including Camptosar (CPT-11) restore TRAIL sensitivity. However, the signaling pathways in restoring TRAIL sensitivity remain to be elucidated. Here, we ... More
Functional analysis of the rat N-methyl-D-aspartate receptor 2A promoter: multiple transcription starts points, positive regulation by Sp factors, and translational regulation.
AuthorsLiu A, Zhuang Z, Hoffman PW, Bai G,
JournalJ Biol Chem
PubMed ID12746457
'N-Methyl-d-aspartate (NMDA) receptor subunit 2A (NR2A) is an important modulatory component of the NMDA subtype of glutamate receptors. To investigate the transcription mechanism of the NR2A gene, we cloned the 5''-flanking sequence from a rat genomic library. RNA mapping with rat brain RNA revealed two sets of major and several ... More
Core protein dependence of epimerization of glucuronosyl residues in galactosaminoglycans.
Authors Seidler Daniela G; Breuer Egon; Grande-Allen K Jane; Hascall Vincent C; Kresse Hans;
JournalJ Biol Chem
PubMed ID12207034
'Chondroitin sulfate and dermatan sulfate proteoglycans are distinguished by differences in their proportion of d-glucuronosyl and l-iduronosyl residues, the latter being formed by chondroitin-glucuronate 5-epimerase during or after glycosaminoglycan chain polymerization. To investigate the influence of the core protein on the extent of epimerization, we expressed chimeric proteins in 293 ... More
A Golgi-associated PDZ domain protein modulates cystic fibrosis transmembrane regulator plasma membrane expression.
Authors Cheng Jie; Moyer Bryan D; Milewski Michal; Loffing Johannes; Ikeda Masahiro; Mickle John E; Cutting Garry R; Li Min; Stanton Bruce A; Guggino William B;
JournalJ Biol Chem
PubMed ID11707463
'We identified a novel cystic fibrosis transmembrane conductance regulator (CFTR)-associating, PDZ domain-containing protein, CAL (CFTR associated ligand) containing two predicted coiled-coiled domains and one PDZ domain. The PDZ domain of CAL binds to the C terminus of CFTR. Although CAL does not have any predicted transmembrane domains, CAL is associated ... More
Endostatin causes G1 arrest of endothelial cells through inhibition of cyclin D1.
'Endostatin, a type XVIII collagen fragment, is a potent antiangiogenic molecule that inhibits endothelial cell migration, promotes apoptosis, and induces cell cycle arrest in vitro. We have investigated the mechanism by which endostatin causes G(1) arrest in endothelial cells. Endostatin decreased the hyperphosphorylated retinoblastoma gene product and down-regulated cyclin D1 ... More
Reduction in intracellular calcium levels inhibits myoblast differentiation.
Authors Porter George A Jr; Makuck Ryan F; Rivkees Scott A;
JournalJ Biol Chem
PubMed ID12042317
'In myocytes, calcium plays an important role in intracellular signaling and contraction. However, the ability of calcium to modulate the differentiation of striated muscle cells is poorly understood. To examine this issue we studied C2C12 cells, which is a myoblast cell line that differentiates in vitro. First, we observed that ... More
Silencing of RNA helicase II/Gualpha inhibits mammalian ribosomal RNA production.
AuthorsHenning D, So RB, Jin R, Lau LF, Valdez BC,
JournalJ Biol Chem
PubMed ID14559904
'The intricate production of ribosomal RNA is well defined in yeast, but its complexity in higher organisms is barely understood. We recently showed that down-regulation of nucleolar protein RNA helicase II/Gualpha (RH-II/Gualpha or DDX21) in Xenopus oocytes inhibited processing of 20 S rRNA to 18 S and contributed to degradation ... More
Selective activation of small GTPase RhoA by tyrosine kinase Etk through its pleckstrin homology domain.
AuthorsKim O, Yang J, Qiu Y.
JournalJ Biol Chem
PubMed ID12023958
'Etk/Bmx is a member of the Btk family tyrosine kinase, which contains an N-terminal pleckstrin homology domain. Etk has been shown to play a pivotal role in the regulation of various cellular processes including differentiation, apoptosis, and cell motility. Here we present evidence that Etk is a modulator of the ... More
Molecular cloning and identification of 3'-phosphoadenosine 5'-phosphosulfate transporter.
AuthorsKamiyama S, Suda T, Ueda R, Suzuki M, Okubo R, Kikuchi N, Chiba Y, Goto S, Toyoda H, Saigo K, Watanabe M, Narimatsu H, Jigami Y, Nishihara S,
JournalJ Biol Chem
PubMed ID12716889
'Nucleotide sulfate, namely 3''-phosphoadenosine 5''-phosphosulfate (PAPS), is a universal sulfuryl donor for sulfation. Although a specific PAPS transporter is present in Golgi membrane, no study has reported the corresponding gene. We have identified a novel human gene encoding a PAPS transporter, which we have named PAPST1, and the Drosophila melanogaster ... More
Positive and negative regulation of APP amyloidogenesis by sumoylation.
AuthorsLi Y, Wang H, Wang S, Quon D, Liu YW, Cordell B,
JournalProc Natl Acad Sci U S A
PubMed ID12506199
'Amyloid beta peptide (Abeta) generated from amyloid precursor protein (APP) is central to Alzheimer''s disease (AD). Signaling pathways affecting APP amyloidogenesis play critical roles in AD pathogenesis and can be exploited for therapeutic intervention. Here, we show that sumoylation, covalent modification of cellular proteins by small ubiquitin-like modifier (SUMO) proteins, ... More
Chromatin structural analyses of the mouse Igkappa gene locus reveal new hypersensitive sites specifying a transcriptional silencer and enhancer.
'To identify new regulatory elements within the mouse Igkappa locus, we have mapped DNase I hypersensitive sites (HSs) in the chromatin of B cell lines arrested at different stages of differentiation. We have focused on two regions encompassing 50 kilobases suspected to contain new regulatory elements based on our previous ... More
Defective ureagenesis in mice carrying a liver-specific disruption of hepatocyte nuclear factor 4alpha (HNF4alpha ). HNF4alpha regulates ornithine transcarbamylase in vivo.
Authors Inoue Yusuke; Hayhurst Graham P; Inoue Junko; Mori Masataka; Gonzalez Frank J;
JournalJ Biol Chem
PubMed ID11994307
'Hepatocyte nuclear factor 4alpha (HNF4alpha) regulates the expression of many genes preferentially expressed in liver. HNF4alpha-null mice die during embryogenesis precluding the analysis of its function in the adult. To circumvent this problem, liver-specific HNF4alpha-null mice were produced. Mice lacking hepatic HNF4alpha expression exhibited increased serum ammonia and reduced serum ... More
Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient mice.
Authors Alexopoulou Lena; Thomas Venetta; Schnare Markus; Lobet Yves; Anguita Juan; Schoen Robert T; Medzhitov Ruslan; Fikrig Erol; Flavell Richard A;
JournalNat Med
PubMed ID12091878
'The Lyme disease vaccine is based on the outer-surface lipoprotein (OspA) of the pathogen Borrelia burgdorferi, and 95% of vaccine recipients develop substantial titers of antibodies against OspA. Here, we identified seven individuals with very low antibody titers after vaccination (low responders). The macrophages of low responders produced less tumor ... More
Random walk of processive, quantum dot-labeled myosin Va molecules within the actin cortex of COS-7 cells.
AuthorsNelson SR, Ali MY, Trybus KM, Warshaw DM,
JournalBiophys J
PubMed ID19619465
'Myosin Va (myoVa) is an actin-based intracellular cargo transporter. In vitro experiments have established that a single myoVa moves processively along actin tracks, but less is known about how this motor operates within cells. Here we track the movement of a quantum dot (Qdot)-labeled myoVa HMM in COS-7 cells using ... More
Molecular cloning and characterization of a novel UDP-Gal:GalNAc(alpha) peptide beta 1,3-galactosyltransferase (C1Gal-T2), an enzyme synthesizing a core 1 structure of O-glycan.
AuthorsKudo T, Iwai T, Kubota T, Iwasaki H, Takayma Y, Hiruma T, Inaba N, Zhang Y, Gotoh M, Togayachi A, Narimatsu H,
JournalJ Biol Chem
PubMed ID12361956
'Recently, a UDP-Gal:GalNAc(alpha) peptide beta1,3-galactosyltransferase (core 1 synthase 1; C1Gal-T1) has been purified from rat liver and its complementary DNA cloned from several species. We isolated a second candidate for core 1 synthase from a Colo205 cDNA library and named it C1Gal-T2. The deduced amino acid sequence of C1Gal-T2, having ... More
Bid sensitizes apoptosis induced by chemotherapeutic drugs in hepatocellular carcinoma.
AuthorsMiao J, Chen GG, Chun SY, Chak EC, Lai PB,
JournalInt J Oncol
PubMed ID15289866
'Hepatocellular carcinoma (HCC) is one of the most common malignancies in Asia. HCC is often resistant to chemotherapy and the mechanism remains unclear. Mitochondrion-mediated pathway is critical in hepatocyte apoptosis, which suggests Bcl-2 family genes may play a role in the regulation of chemotherapy in HCC. In the present study, ... More
Identification of Protein Arginine Methyltransferase 2 as a Coactivator for Estrogen Receptor alpha.
'In an attempt to isolate cofactors capable of influencing estrogen receptor alpha (ERalpha) transcriptional activity, we used yeast two-hybrid screening and identified protein arginine methyltransferase 2 (PRMT2) as a new ERalpha-binding protein. PRMT2 interacted directly with three ERalpha regions including AF-1, DNA binding domain, and hormone binding domain in a ... More
Multiple domains of MCIP1 contribute to inhibition of calcineurin activity.
AuthorsVega RB, Yang J, Rothermel BA, Bassel-Duby R, Williams RS.
JournalJ Biol Chem
PubMed ID12063245
'Calcineurin is a serine/threonine protein phosphatase that plays a critical role in many physiologic processes such as T-cell activation, apoptosis, skeletal myocyte differentiation, and cardiac hypertrophy. Calcineurin-dependent signals are transduced to the nucleus by nuclear factor of activated T-cells (NFAT) transcription factors that undergo nuclear translocation upon dephosphorylation and promote ... More
A role of the C-terminal region of human Rad9 (hRad9) in nuclear transport of the hRad9 checkpoint complex.
Authors Hirai Itaru; Wang Hong-Gang;
JournalJ Biol Chem
PubMed ID11994305
'Rad9, Rad1, and Hus1 are members of the Rad family of checkpoint proteins that are required for both DNA replication and DNA damage checkpoints and are thought to function as sensors in the DNA integrity checkpoint control. These proteins can interact with each other and form a stable proliferating cell ... More
Alzheimer's disease-associated presenilin 2 interacts with DRAL, an LIM-domain protein.
Authors Tanahashi H; Tabira T;
JournalHum Mol Genet
PubMed ID11001931
'Using the yeast two-hybrid system, we screened for proteins interacting with presenilin 2 (PS2) and cloned DRAL. DRAL is an LIM-only protein containing four LIM domains and an N-terminal half LIM domain. Previously DRAL has been cloned as a co-activator of the androgen receptor and as a protein interacting with ... More
Linking beta-catenin to androgen-signaling pathway.
Authors Yang Fajun; Li Xiaoyu; Sharma Manju; Sasaki Carl Y; Longo Dan L; Lim Bing; Sun Zijie;
JournalJ Biol Chem
PubMed ID11792709
'The androgen-signaling pathway is important for the growth and progression of prostate cancer cells. The growth-promoting effects of androgen on prostate cells are mediated mostly through the androgen receptor (AR). There is increasing evidence that transcription activation by AR is mediated through interaction with other cofactors. beta-Catenin plays a critical ... More
Phosphatidylinositol 3-kinase and Src family kinases are required for phosphorylation and membrane recruitment of Dok-1 in c-Kit signaling.
'Dok-1 is an adaptor protein that is a substrate for Bcr-Abl and other tyrosine protein kinases. The presence of pleckstrin homology and phosphotyrosine binding domains as well as multiple tyrosine phosphorylation sites suggests that Dok-1 is involved in protein-protein and/or protein-lipid interactions. Here we show that stimulation of Mo7 hematopoietic ... More
'The peroxisome proliferator-activated receptors (PPAR) alpha and gamma play key roles in the transcriptional control of contrasting metabolic pathways such as adipogenesis and fatty acid beta-oxidation. Both ligand-activated nuclear receptors bind to common target gene response elements and interact with distinct domains of the transcriptional coactivator PGC-1 to attain their ... More
Dual fluorescent labeling method to visualize plasmid DNA degradation.
'The efficiency of nonviral vectors for gene delivery may be enhanced by understanding the key barriers that limit the translocation of the therapeutic DNA into the nucleus. One such barrier is the instability of DNA in the cytoplasm. In this work, we have developed a method to dual-label plasmid DNA ... More
The spectrin cytoskeleton influences the surface expression and activation of human transient receptor potential channel 4 channels.
AuthorsOdell AF, Van Helden DF, Scott JL,
JournalJ Biol Chem
PubMed ID18048348
'Despite over a decade of research, only recently have the mechanisms governing transient receptor potential channel (TRPC) channel function begun to emerge, with an essential role for accessory proteins in this process. We previously identified a tyrosine phosphorylation event as critical in the plasma membrane translocation and activation of hTRPC4 ... More
Sustained production of H(2)O(2) activates pro-matrix metalloproteinase-2 through receptor tyrosine kinases/phosphatidylinositol 3-kinase/NF-kappa B pathway.
AuthorsYoon SO, Park SJ, Yoon SY, Yun CH, Chung AS.
JournalJ Biol Chem
PubMed ID12058032
'A rate-limiting step of tumor cell metastasis is matrix degradation by active matrix metalloproteinases (MMPs). It is known that reactive oxygen species are involved in tumor metastasis. Sustained production of H(2)O(2) by phenazine methosulfate (PMS) induced activation of pro-MMP-2 through the induction of membrane type 1-MMP (MT1-MMP) expression in HT1080 ... More
Intensity calibration and automated cell cycle gating for high-throughput image-based siRNA screens of mammalian cells.
AuthorsPoon SS, Wong JT, Saunders DN, Ma QC, McKinney S, Fee J, Aparicio SA,
JournalCytometry A
PubMed ID18698634
'High-content microscopic screening systems are powerful tools for extracting quantitative multiparameter measures from large number of cells under numerous conditions. These systems perform well in applications that monitor the presence of objects, but lack in their ability to accurately estimate object intensities and summarize these findings due to variations in ... More
Genetic analysis of the herpes simplex virus type 1 UL20 protein domains involved in cytoplasmic virion envelopment and virus-induced cell fusion.
AuthorsMelancon JM, Foster TP, Kousoulas KG,
JournalJ Virol
PubMed ID15220406
'The herpes simplex virus type 1 UL20 protein (UL20p) is an important determinant for cytoplasmic virion morphogenesis and virus-induced cell fusion. To delineate the functional domains of the UL20 protein, we generated a panel of single and multiple (cluster) alanine substitutions as well as UL20p carboxyl-terminal truncations. The UL20 mutant ... More
Megakaryoblastic leukemia factor-1 transduces cytoskeletal signals and induces smooth muscle cell differentiation from undifferentiated embryonic stem cells.
AuthorsDu KL, Chen M, Li J, Lepore JJ, Mericko P, Parmacek MS,
JournalJ Biol Chem
PubMed ID14970199
'The SAP domain transcription factor myocardin plays a critical role in the transcriptional program regulating smooth muscle cell differentiation. In this report, we describe the capacity of myocardin to physically associate with megakaryoblastic leukemia factor-1 (MKL1) and characterize the function of MKL1 in smooth muscle cells (SMCs). The MKL1 gene ... More
A macromolecular complex of beta 2 adrenergic receptor, CFTR, and ezrin/radixin/moesin-binding phosphoprotein 50 is regulated by PKA.
AuthorsNaren AP, Cobb B, Li C, Roy K, Nelson D, Heda GD, Liao J, Kirk KL, Sorscher EJ, Hanrahan J, Clancy JP,
JournalProc Natl Acad Sci U S A
PubMed ID12502786
'It has been demonstrated previously that both the cystic fibrosis transmembrane conductance regulator (CFTR) and beta(2) adrenergic receptor (beta(2)AR) can bind ezrinradixinmoesin-binding phosphoprotein 50 (EBP50, also referred to as NHERF) through their PDZ motifs. Here, we show that beta(2) is the major adrenergic receptor isoform expressed in airway epithelia and ... More
Interacting effects of N-terminal variation and strex exon splicing on slo potassium channel regulation by calcium, phosphorylation, and oxidation.
Authors Erxleben Christian; Everhart Angela L; Romeo Charles; Florance Hannah; Bauer Mary Beth; Alcorta David A; Rossie Sandra; Shipston Michael J; Armstrong David L;
JournalJ Biol Chem
PubMed ID12016222
'We have investigated the structural basis for the phenotype of a native rat Slo (rSlo) potassium channel (BK(Ca); KCNMA1) in a rat pituitary cell line, GH(4)C(1). Opposing regulation of these calcium- and voltage-activated potassium channels by cAMP- and cGMP-dependent protein kinases requires an alternatively spliced exon (strex) of 59 amino ... More
Tpl2 phosphorylation at Thr290 is induced by LPS via an IKKbeta -dependent pathway and is required for Tpl2 activation by external signals.
AuthorsCho J, Melnick M, Solidakis GP, Tsichlis PN,
JournalJ Biol Chem
PubMed ID15778223
'The serine-threonine protein kinase encoded by the Tpl2 proto-oncogene transduces Toll like receptor and death receptor signals in a variety of cell types. Here we show that Tpl2 undergoes phosphorylation at Thr290 both in cells overexpressing Tpl2, as well as in cells stimulated with LPS or TNF-alpha, and that phosphorylation ... More
The RasGAP N-terminal fragment generated by caspase cleavage protects cells in a Ras/PI3K/Akt-dependent manner that does not rely on NFkappa B activation.
Authors Yang Jiang-Yan; Widmann Christian;
JournalJ Biol Chem
PubMed ID11847220
'RasGAP, a regulator of Ras GTPase family members, is cleaved at low levels of caspase activity into an N-terminal fragment (fragment N) that generates potent anti-apoptotic signals. At higher levels of caspase activity, fragment N is further cleaved into two fragments that strongly potentiate apoptosis. RasGAP could thus function as ... More
A pro-apoptotic fragment of the p75 neurotrophin receptor is expressed in p75NTRExonIV null mice.
AuthorsPaul CE, Vereker E, Dickson KM, Barker PA,
JournalJ Neurosci
PubMed ID14985432
'The p75 neurotrophin receptor (p75NTR) regulates neuronal survival, apoptosis, and growth. Recent studies have reported that disruption of Exon IV produces a null mouse lacking all p75NTR gene products (p75NTRExonIV-/-), whereas mice lacking p75NTR Exon III (p75NTRExonIII-/-) maintain expression of an alternatively spliced form of p75NTR (s-p75NTR). Here, we report ... More
The ebola virus VP35 protein functions as a type I IFN antagonist
AuthorsBasler CF, Wang X, Muhlberger E, Volchkov V, Paragas J, Klenk HD, Garcia-Sastre A, Palese P
JournalProc Natl Acad Sci U S A
PubMed ID11027311
'An assay has been developed that allows the identification of molecules that function as type I IFN antagonists. Using this assay, we have identified an Ebola virus-encoded inhibitor of the type I IFN response, the Ebola virus VP35 protein. The assay relies on the properties of an influenza virus mutant, ... More
A carboxyl-terminal PDZ-interacting domain of scavenger receptor B, type I is essential for cell surface expression in liver.
Authors Silver David L;
JournalJ Biol Chem
PubMed ID12119305
'Scavenger receptor B, type I (SR-BI) was recently shown to interact with a PDZ domain-containing protein, PDZK1 (CLAMP/Diphor-1/CAP70/NaPi-Cap1), but the importance of this interaction in vivo in terms of SR-BI function has not been determined. In an effort to elucidate the role of this interaction in vivo, the PDZK1-interacting domain ... More
Distinct residues in the carboxyl tail mediate agonist-induced desensitization and internalization of the human dopamine D1 receptor.
Authors Lamey Michael; Thompson Miles; Varghese George; Chi Hong; Sawzdargo Marek; George Susan R; O'Dowd Brian F;
JournalJ Biol Chem
PubMed ID11773080
'We have shown in a previous study that desensitization and internalization of the human dopamine D(1) receptor following short-term agonist exposure are mediated by temporally and biochemically distinct mechanisms. In the present study, we have used site-directed mutagenesis to remove potential phosphorylation sites in the third intracellular loop and carboxyl ... More
Interferons inhibit tumor necrosis factor-alpha-mediated matrix metalloproteinase-9 activation via interferon regulatory factor-1 binding competition with NF-kappa B.
'Enhanced expression of matrix metalloproteinase-9 (MMP-9) correlates with invasion during tumor progression. Interferons (IFNs) inhibit MMP-9 activation in response to tumor necrosis factor-alpha (TNF-alpha), and the latter activates the MMP-9 gene through NF-kappaB. Understanding the molecular basis for MMP-9 inhibition may provide tools to control cell invasion. The data reported ... More
The role of phosphatidylinositol 3-kinase, rho family GTPases, and STAT3 in Ros-induced cell transformation.
Authors Nguyen Kevin T; Zong Cong S; Uttamsingh Shailaja; Sachdev Pallavi; Bhanot Monica; Le Mai-Thao; Chan Joseph L-K; Wang Lu-Hai;
JournalJ Biol Chem
PubMed ID11799110
'Using loss-of-function mutants of Ros and inducible epidermal growth factor receptor-Ros chimeras we investigated the role of various signaling pathways in Ros-induced cell transformation. Inhibition of the mitogen-activated protein kinase (MAPK) pathway with the MEK (MAP/extracellular signal-regulated kinase kinase) inhibitor PD98059 had little effect on the Ros-induced monolayer and anchorage-independent ... More
Germ Cell Nuclear Factor Is a Repressor of CRIPTO-1 and CRIPTO-3.
AuthorsHentschke M, Kurth I, Borgmeyer U, Hübner CA,
JournalJ Biol Chem
PubMed ID16954206
'The pluripotency of embryonic stem and embryonic carcinoma cells is maintained by the expression of a set of '
Differentiation of embryonic stem cells is induced by GATA factors.
'Extraembryonic endoderm (ExE) is differentiated from the inner cell mass of the late blastocyst-stage embryo to form visceral and parietal endoderm, both of which have an important role in early embryogenesis. The essential roles of Gata-6 and Gata-4 on differentiation of visceral endoderm have been identified by analyses of knockout ... More
Protein phosphatase 2A holoenzyme assembly: identification of contacts between B-family regulatory and scaffolding A subunits.
Authors Strack Stefan; Ruediger Ralf; Walter Gernot; Dagda Ruben K; Barwacz Chris A; Cribbs J Thomas;
JournalJ Biol Chem
PubMed ID11929880
'Protein serine/threonine phosphatase (PP) 2A is a ubiquitous enzyme with pleiotropic functions. Trimeric PP2A consists of a structural A subunit, a catalytic C subunit, and a variable regulatory subunit. Variable subunits (B, B'', and B' ... More
Altered kinetics and benzodiazepine sensitivity of a GABAA receptor subunit mutation [gamma 2(R43Q)] found in human epilepsy.
Authors Bowser David N.; Wagner David A.; Czajkowski Cynthia; Cromer Brett A.; Parker Michael W.; Wallace Robyn H.; Harkin Louise A.; Mulley John C.; Marini Carla; Berkovic Samuel F.; Williams David A.; Jones Mathew V.; Petrou Steven;
JournalProc Natl Acad Sci U S A
PubMed ID12415111
'The gamma-aminobutyric acid type A (GABA(A)) receptor mediates fast inhibitory synaptic transmission in the CNS. Dysfunction of the GABA(A) receptor would be expected to cause neuronal hyperexcitability, a phenomenon linked with epileptogenesis. ' ... More
The novel WD-repeat protein MORG1 acts as a molecular scaffold for HIF prolyl-hydroxylase 3 (PHD3).
AuthorsHopfer U, Hopfer H, Jablonski K, Stahl RA, Wolf G,
JournalJ Biol Chem
PubMed ID16407229
'Hypoxia-inducible factor-1 (HIF-1), a transcriptional complex composed of an oxygen-sensitive alpha- and a beta-subunit, plays a pivotal role in cellular adaptation to low oxygen availability. Under normoxia, the alpha-subunit of HIF-1 is hydroxylated by a family of prolyl hydroxylases (PHDs) and consequently targeted for proteasomal degradation. Three different prolyl hydroxylases ... More
Pathological mutations in TSC1 and TSC2 disrupt the interaction between hamartin and tuberin.
'Critical functions of hamartin and tuberin, encoded by the TSC1 and TSC2 genes, are likely to be closely linked. The proteins interact directly with one another and mutations affecting either gene result in the tuberous sclerosis phenotype. However, the regions of hamartin and tuberin that interact have not been well ... More
Estrogen receptor-interacting protein that modulates its nongenomic activity-crosstalk with Src/Erk phosphorylation cascade.
Authors Wong Chi-Wai; McNally Christopher; Nickbarg Elliot; Komm Barry S; Cheskis Boris J;
JournalProc Natl Acad Sci U S A
PubMed ID12415108
'Numerous studies have demonstrated that estrogens induce rapid and transient activation of the Src/Erk phosphorylation cascade. Activation of this cascade triggers vital cellular functions including cell proliferation and differentiation. However, the details of the molecular mechanism of this process remain to be elucidated. We have identified a previously uncharacterized nuclear ... More
Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signaling.
AuthorsBaba M, Hong SB, Sharma N, Warren MB, Nickerson ML, Iwamatsu A, Esposito D, Gillette WK, Hopkins RF, Hartley JL, Furihata M, Oishi S, Zhen W, Burke TR, Linehan WM, Schmidt LS, Zbar B,
JournalProc Natl Acad Sci U S A
PubMed ID17028174
'Birt-Hogg-Dubé syndrome, a hamartoma disorder characterized by benign tumors of the hair follicle, lung cysts, and renal neoplasia, is caused by germ-line mutations in the BHD(FLCN) gene, which encodes a tumor-suppressor protein, folliculin (FLCN), with unknown function. The tumor-suppressor proteins encoded by genes responsible for several other hamartoma syndromes, LKB1, ... More
Hepatitis C virus subgenomic replicons in the human embryonic kidney 293 cell line.
AuthorsAli S, Pellerin C, Lamarre D, Kukolj G,
JournalJ Virol
PubMed ID14671129
'Hepatitis C virus (HCV) infects liver cells and its replication in other cells is incompletely defined. Human hepatoma Huh-7 cells harboring subgenomic HCV replicons were used in somatic cell fusion experiments with human embryonic kidney 293 cells as a means of examining the permissiveness of 293 cells for HCV subgenomic ... More
The aspartate-257 of presenilin 1 is indispensable for mouse development and production of beta-amyloid peptides through beta-catenin-independent mechanisms.
Authors Xia Xuefeng; Wang Pei; Sun Xiaoyan; Soriano Salvador; Shum Wan-Kyng; Yamaguchi Haruyasu; Trumbauer Myrna E; Takashima Akihiko; Koo Edward H; Zheng Hui;
JournalProc Natl Acad Sci U S A
PubMed ID12070348
'To differentiate multiple activities of presenilin 1 (PS1), we generated transgenic mice expressing two human PS1 alleles: one with the aspartate to alanine mutation at residue 257 (hPS1D257A) that impairs the proteolytic activity of PS1, and the other deleting amino acids 340-371 of the hydrophilic loop sequence (hPS1Deltacat) essential for ... More
PKD1 Induces p21(waf1) and Regulation of the Cell Cycle via Direct Activation of the JAK-STAT Signaling Pathway in a Process Requiring PKD2.
'Autosomal dominant polycystic kidney disease is characterized by cyst formation in the kidney and other organs and results from mutations of PKD1 or PKD2. Previous studies suggest that their gene products have an important role in growth regulation. We now show that expression of polycystin-1 activates the JAK-STAT pathway, thereby ... More
Enhanced gene silencing of HIV-1 specific siRNA using microRNA designed hairpins.
AuthorsBoden D, Pusch O, Silbermann R, Lee F, Tucker L, Ramratnam B,
JournalNucleic Acids Res
PubMed ID14966264
'Post-transcriptional inhibition of HIV-1 replication can be achieved by RNA interference (RNAi). The cellular expression of short interfering RNA (siRNA) or short hairpin RNA (shRNA) homologous to regions of the HIV-1 genome decreases viral replication by the selective degradation of targeted RNA. Here, we demonstrate that another class of noncoding ... More
The cytoplasmic tail dileucine motif LL572 determines the glycosylation pattern of membrane-type 1 matrix metalloproteinase.
'Membrane-type 1 matrix metalloproteinase (MT1-MMP; MMP-14) drives fundamental physiological and pathological processes, due to its ability to process a broad spectrum of substrates. Because subtle changes in its activity can produce profound physiological effects, MT1-MMP is tightly regulated. Currently, many aspects of this regulation remain to be elucidated. It has ... More
The human GINS complex associates with Cdc45 and MCM and is essential for DNA replication.
AuthorsAparicio T, Guillou E, Coloma J, Montoya G, Méndez J,
JournalNucleic Acids Res
PubMed ID19223333
'The GINS complex, originally discovered in Saccharomyces cerevisiae and Xenopus laevis, binds to DNA replication origins shortly before the onset of S phase and travels with the replication forks after initiation. In this study we present a detailed characterization of the human GINS (hGINS) homolog. Using new antibodies that allow ... More
EphA4-mediated Rho activation via Vsm-RhoGEF expressed specifically in vascular smooth muscle cells.
AuthorsOgita H, Kunimoto S, Kamioka Y, Sawa H, Masuda M, Mochizuki N,
JournalCirc Res
PubMed ID12775584
'Rho-kinase, an effector of Rho GTPase, increases the contractility of vascular smooth muscle by phosphorylating myosin light chain (MLC) and by inactivating MLC phosphatase. A wide variety of extracellular stimuli activate RhoA via G protein-coupled receptors. In the present study, we demonstrate a novel cell-cell interaction-mediated Rho activation signaling pathway ... More
Trpm7 regulates cell adhesion by controlling the calcium dependent protease calpain.
AuthorsSu LT, Agapito MA, Li M, T N Simonson W, Huttenlocher A, Habas R, Yue L, Runnels LW,
JournalJ Biol Chem
PubMed ID16436382
'M-calpain is a protease implicated in the control of cell adhesion through focal adhesion disassembly. The mechanism by which the enzyme is spatially and temporally controlled is not well understood, particularly because calpain''s dependence on calcium exceeds the sub-micromolar concentrations normally observed in cells. Here we show that the channel-kinase ... More
CD147 is a regulatory subunit of the gamma-secretase complex in Alzheimer's disease amyloid beta-peptide production.
AuthorsZhou S, Zhou H, Walian PJ, Jap BK,
JournalProc Natl Acad Sci U S A
PubMed ID15890777
'gamma-Secretase is a membrane protein complex that cleaves the beta-amyloid precursor protein (APP) within the transmembrane region, after prior processing by beta-secretase, producing amyloid beta-peptides Abeta(40) and Abeta(42). Errant production of Abeta-peptides that substantially increases Abeta(42) production has been associated with the formation of amyloid plaques in Alzheimer''s disease patients. ... More
A Novel Diacylglycerol-lactone Shows Marked Selectivity in Vitro among C1 Domains of Protein Kinase C (PKC) Isoforms {alpha} and {delta} as Well as Selectivity for RasGRP Compared with PKC{alpha}.
AuthorsPu Y, Perry NA, Yang D, Lewin NE, Kedei N, Braun DC, Choi SH, Blumberg PM, Garfield SH, Stone JC, Duan D, Marquez VE,
JournalJ Biol Chem
PubMed ID15923197
'Although multiple natural products are potent ligands for the diacylglycerol binding C1 domain of protein kinase C (PKC), RasGRP, and related targets, the high conservation of C1 domains has impeded the development of selective ligands. We characterized here a diacylglycerol-lactone, 130C037, emerging from a combinatorial chemical synthetic strategy, which showed ... More
Identification of FEZ1 as a protein that interacts with JC virus agnoprotein and microtubules: role of agnoprotein-induced dissociation of FEZ1 from microtubules in viral propagation.
AuthorsSuzuki T, Okada Y, Semba S, Orba Y, Yamanouchi S, Endo S, Tanaka S, Fujita T, Kuroda S, Nagashima K, Sawa H,
JournalJ Biol Chem
PubMed ID15843383
'The human polyomavirus JC virus (JCV) is the causative agent of a fatal demyelinating disease, progressive multifocal leukoencephalopathy, and encodes six major proteins, including agnoprotein. Agnoprotein colocalizes with microtubules in JCV-infected cells, but its function is not fully understood. We have now identified fasciculation and elongation protein zeta 1 (FEZ1) ... More
Derlin-1 promotes the efficient degradation of CFTR and CFTR folding mutants.
'A complex involving Derlin-1 and p97 mediates the retrotranslocation and endoplasmic reticulum associated degradation (ERAD) of misfolded proteins in yeast and is used by certain viruses to promote host cell protein degradation (1-3). We asked whether they are involved in the ERAD of the mammalian integral membrane protein, CFTR, a ... More
Accelerated discovery of synthetic transfection vectors: parallel synthesis and screening of a degradable polymer library.
Authors Lynn D M; Anderson D G; Putnam D; Langer R;
JournalJ Am Chem Soc
PubMed ID11506588
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Coculture methodologies for the study of Wnt signals.
AuthorsPlanutis K, Planutiene M, Holcombe RF,
JournalMethods Mol Biol
PubMed ID19099261
In vivo, responses to extracellular Wnt ligands are context dependent; the temporal characteristics and intensity of the signal are critical in determining the target cell response. In general, Wnt ligand-induced differentiation in mammalian cells requires several days of exposure. In order to better characterize Wnt-induced signaling in vitro, side-by-side and ... More
Targeted disruption of Np95 gene renders murine embryonic stem cells hypersensitive to DNA damaging agents and DNA replication blocks.
NP95, which contains a ubiquitin-like domain, a cyclin A/E-Cdk2 phosphorylation site, a retinoblastoma (Rb) binding motif, and a ring finger domain, has been shown to be colocalized as foci with proliferating cell nuclear antigen in early and mid-S phase nuclei. We established Np95 nulligous embryonic stem cells by replacing the ... More
The calcium-binding loops of the tandem C2 domains of synaptotagmin VII cooperatively mediate calcium-dependent oligomerization.
Synaptotagmin VII (Syt VII), a proposed regulator for Ca2+-dependent exocytosis, showed a robust Ca2+-dependent oligomerization property via its two C2 domains (Fukuda, M., and Mikoshiba, K. (2001) J. Biol. Chem. 276, 27670-27676), but little is known about its structure or the critical residues directly involved in the oligomerization interface. In ... More
alpha-Actinin interacts with rapsyn in agrin-stimulated AChR clustering.
AuthorsDobbins GC, Luo S, Yang Z, Xiong WC, Mei L,
JournalMol Brain
PubMed ID19055765
: AChR is concentrated at the postjunctional membrane at the neuromuscular junction. However, the underlying mechanism is unclear. We show that alpha-actinin, a protein known to cross-link F-actin, interacts with rapsyn, a scaffold protein essential for neuromuscular junction formation. alpha-Actinin, rapsyn, and surface AChR form a ternary complex. Moreover, the ... More
SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein.
Helicobacter pylori CagA protein is associated with severe gastritis and gastric carcinoma. CagA is injected from the attached Helicobacter pylori into host cells and undergoes tyrosine phosphorylation. Wild-type but not phosphorylation-resistant CagA induced a growth factor-like response in gastric epithelial cells. Furthermore, CagA formed a physical complex with the SRC ... More
Mechanism of c-Myb-C/EBPbeta Cooperation from Separated Sites on a Promoter.
c-Myb, but not avian myeloblastosis virus (AMV) v-Myb, cooperates with C/EBPbeta to regulate transcription of myeloid-specific genes. To assess the structural basis for that difference, we determined the crystal structures of complexes comprised of the c-Myb or AMV v-Myb DNA-binding domain (DBD), the C/EBPbeta DBD, and a promoter DNA fragment. ... More
Rapid induction of dendritic spine morphogenesis by trans-synaptic ephrinB-EphB receptor activation of the Rho-GEF kalirin.
AuthorsPenzes P, Beeser A, Chernoff J, Schiller MR, Eipper BA, Mains RE, Huganir RL,
JournalNeuron
PubMed ID12546821
The morphogenesis of dendritic spines, the major sites of excitatory synaptic transmission in the brain, is important in synaptic development and plasticity. We have identified an ephrinB-EphB receptor trans-synaptic signaling pathway which regulates the morphogenesis and maturation of dendritic spines in hippocampal neurons. Activation of the EphB receptor induces translocation ... More
Requirement of the p130CAS-Crk coupling for metastasis suppressor KAI1/CD82-mediated inhibition of cell migration.
AuthorsZhang XA, He B, Zhou B, Liu L,
JournalJ Biol Chem
PubMed ID12738793
KAI1/CD82 protein is a member of the tetraspanin superfamily and has been rediscovered as a cancer metastasis suppressor. The mechanism of KAI1/CD82-mediated suppression of cancer metastasis remains to be established. In this study, we found that migration of the metastatic prostate cancer cell line Du145 was substantially inhibited when KAI1/CD82 ... More
The nephroblastoma overexpressed gene (NOV/ccn3) protein associates with Notch1 extracellular domain and inhibits myoblast differentiation via Notch signaling pathway.
AuthorsSakamoto K, Yamaguchi S, Ando R, Miyawaki A, Kabasawa Y, Takagi M, Li CL, Perbal B, Katsube K.
JournalJ Biol Chem
PubMed ID12050162
We demonstrate a novel interaction of the nephroblastoma overexpressed gene (NOV), a member of the CCN gene family, with the Notch signaling pathway. NOV associates with the epidermal growth factor-like repeats of Notch1 by the CT (C-terminal cysteine knot) domain. The promoters of HES1 and HES5, which are the downstream ... More
Evolution of human-chimpanzee differences in malaria susceptibility: relationship to human genetic loss of N-glycolylneuraminic acid.
AuthorsMartin MJ, Rayner JC, Gagneux P, Barnwell JW, Varki A,
JournalProc Natl Acad Sci U S A
PubMed ID16126901
Chimpanzees are the closest evolutionary cousins of humans, sharing >99% identity in most protein sequences. Plasmodium falciparum is the major worldwide cause of malaria mortality. Plasmodium reichenowi, a morphologically identical and genetically very similar parasite, infects chimpanzees but not humans. Conversely, experimental P. falciparum infection causes brief moderate parasitization and ... More
Corepressors selectively control the transcriptional activity of PPARgamma in adipocytes.
AuthorsGuan HP, Ishizuka T, Chui PC, Lehrke M, Lazar MA,
JournalGenes Dev
PubMed ID15681609
Peroxisome proliferator-activated receptor gamma (PPARgamma) is the master regulator of adipogenesis as well as the target of thiazolidinedione (TZD) antidiabetic drugs. Many PPARgamma target genes are induced during adipogenesis, but others, such as glycerol kinase (GyK), are expressed at low levels in adipocytes and dramatically up-regulated by TZDs. Here, we ... More
Polycistronic RNA polymerase II expression vectors for RNA interference based on BIC/miR-155.
AuthorsChung KH, Hart CC, Al-Bassam S, Avery A, Taylor J, Patel PD, Vojtek AB, Turner DL,
JournalNucleic Acids Res
PubMed ID16614444
Vector-based RNA interference (RNAi) has emerged as a valuable tool for analysis of gene function. We have developed new RNA polymerase II expression vectors for RNAi, designated SIBR vectors, based upon the non-coding RNA BIC. BIC contains the miR-155 microRNA (miRNA) precursor, and we find that expression of a short ... More
NOD2/CARD15 mediates induction of the antimicrobial peptide human beta-defensin-2.
Production of inducible antimicrobial peptides offers a first and rapid defense response of epithelial cells against invading microbes. Human Beta-defensin-2 (hBD-2) is an antimicrobial peptide induced in various epithelia upon extracellular as well as intracellular bacterial challenge. Nucleotide-binding oligomerization domain protein 2 (NOD2/CARD15) is a cytosolic protein involved in intracellular ... More
Ect2 and MgcRacGAP regulate the activation and function of Cdc42 in mitosis.
Although Rho regulates cytokinesis, little was known about the functions in mitosis of Cdc42 and Rac. We recently suggested that Cdc42 works in metaphase by regulating bi-orient attachment of spindle microtubules to kinetochores. We now confirm the role of Cdc42 by RNA interference and identify the mechanisms for activation and ... More
Improved targeting of miRNA with antisense oligonucleotides.
AuthorsDavis S, Lollo B, Freier S, Esau C,
JournalNucleic Acids Res
PubMed ID16690972
MicroRNAs (miRNAs) are a class of 20-24 nt noncoding RNAs that regulate target mRNAs post-transcriptionally by binding with imperfect complementarity in the 3'-untranslated region (3'-UTR) and inhibiting translation or RNA stability. Current understanding of miRNA biology is limited, and antisense oligonucleotide (ASO) inhibition is a powerful technique for miRNA functionalization ... More
Acylation of CD44 and its association with lipid rafts are required for receptor and hyaluronan endocytosis.
AuthorsThankamony SP, Knudson W,
JournalJ Biol Chem
PubMed ID16945930
CD44 is a cell surface receptor for the extracellular matrix macromolecule hyaluronan. In addition, CD44 mediates the endocytosis of hyaluronan leading to its subsequent degradation within lysosomes. Using model systems of COS-7 and Flp-293 cells, we demonstrate that the association of CD44 with lipid rafts is essential for the endocytosis ... More
The expression of Sprouty1, an inhibitor of fibroblast growth factor signal transduction, is decreased in human prostate cancer.
AuthorsKwabi-Addo B, Wang J, Erdem H, Vaid A, Castro P, Ayala G, Ittmann M,
JournalCancer Res
PubMed ID15256439
A considerable body of evidence indicates that alterations of fibroblast growth factors (FGFs) and their receptors contribute to prostate cancer progression. Recently, a new family of regulators of FGF activity has been identified. The Sprouty gene family negatively regulates FGF signaling in a variety of systems and could potentially limit ... More
Mutational analysis of the DEAD-box RNA helicase eIF4AII characterizes its interaction with transformation suppressor Pdcd4 and eIF4GI.
AuthorsZakowicz H, Yang HS, Stark C, Wlodawer A, Laronde-Leblanc N, Colburn NH,
JournalRNA
PubMed ID15661843
Eukaryotic initiation factor (eIF) 4A unwinds secondary and tertiary structures in the 5'-untranslated region of mRNA, permitting translation initiation. Programmed cell death 4 (Pdcd4) is a novel transformation suppressor and eIF4A-binding partner that inhibits eIF4A helicase activity and translation. To elucidate the regions of eIF4A that are functionally significant in ... More
Endocytic function, glycosaminoglycan specificity, and antibody sensitivity of the recombinant human 190-kDa hyaluronan receptor for endocytosis (HARE).
AuthorsHarris EN, Weigel JA, Weigel PH,
JournalJ Biol Chem
PubMed ID15208308
The human hyaluronan receptor for endocytosis (hHARE) mediates the endocytic clearance of hyaluronan (HA) and chondroitin sulfate from lymph fluid and blood. Two hHARE isoforms (190 and 315 kDa) are present in sinusoidal endothelial cells of liver, spleen, and lymph nodes (Zhou, B., McGary, C. T., Weigel, J. A., Saxena, ... More
Identification of a gadd45beta 3' enhancer that mediates SMAD3- and SMAD4-dependent transcriptional induction by transforming growth factor beta.
AuthorsMajor MB, Jones DA,
JournalJ Biol Chem
PubMed ID14630914
GADD45beta regulates cell growth, differentiation, and cell death following cellular exposure to diverse stimuli, including DNA damage and transforming growth factor-beta (TGFbeta). We examined how cells transduce the TGFbeta signal from the cell surface to the gadd45beta genomic locus and describe how GADD45beta contributes to TGFbeta biology. Following an alignment ... More
Notch-1 activation and dendritic atrophy in prion disease.
AuthorsIshikura N, Clever JL, Bouzamondo-Bernstein E, Samayoa E, Prusiner SB, Huang EJ, DeArmond SJ,
JournalProc Natl Acad Sci U S A
PubMed ID15640354
In addition to neuronal vacuolation and astrocytic hypertrophy, dendritic atrophy is a prominent feature of prion disease. Because increased Notch-1 expression and cleavage releasing its intracellular domain (NICD) inhibit both dendrite growth and maturation, we measured their levels in brains from mice inoculated with Rocky Mountain Laboratory (RML) prions. The ... More