WAF1, a potential mediator of p53 tumor suppression.
Authorsel-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW, Vogelstein B
JournalCell
PubMed ID8242752
The ability of p53 to activate transcription from specific sequences suggests that genes induced by p53 may mediate its biological role as a tumor suppressor. Using a subtractive hybridization approach, we identified a gene, named WAF1, whose induction was associated with wild- type but not mutant p53 gene expression in ... More
CC chemokine receptor 5-mediated signaling and HIV-1 Co-receptor activity share common structural determinants. Critical residues in the third extracellular loop support HIV-1 fusion.
'There is a close correspondence between the ability of RANTES and macrophage inflammatory proteins 1alpha and 1beta to activate CC chemokine receptor 5 (CCR5) and the ability to inhibit CCR5-dependent membrane fusion mediated by the envelope glycoprotein of human immunodeficiency virus (HIV), type 1. This finding suggests that some of ... More
Dimerization of a selectin and its ligand stabilizes cell rolling and enhances tether strength in shear flow.
Authors Ramachandran V; Yago T; Epperson T K; Kobzdej M M; Nollert M U; Cummings R D; Zhu C; McEver R P;
JournalProc Natl Acad Sci U S A
PubMed ID11526223
'Selectins mediate rolling of leukocytes by rapid formation and dissociation of selectin-ligand bonds, which are assumed to require high mechanical strength to prevent premature dissociation by the forces applied in shear flow. This assumption is based largely on the observation that increasing wall shear stress increases only modestly the dissociation ... More
Reconstitution of stretch-activated cation channels by expression of the alpha-subunit of the epithelial sodium channel cloned from osteoblasts [published erratum appears in Proc Natl Acad Sci U S A 1997 Apr 15;94(8):4233]
AuthorsKizer N, Guo XL, Hruska K
JournalProc Natl Acad Sci U S A
PubMed ID9023374
'Osteoblasts respond to repetitive strain by activating stretch- activated, nonselective cation channels (SA-CAT) and increasing matrix protein production. SA-CAT channels are thought to be responsible for mechano-transduction in osteoblasts, although the molecular identity of the SA-CAT channel has previously been unknown. We have demonstrated that both the UMR-106 osteoblast-like cell ... 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
Pattern of genes influenced by conditional expression of the transcription factors HNF6, HNF4alpha and HNF1beta in a pancreatic beta-cell line.
'Using the rat insulinoma cell line INS-1 we generated beta-cell clones that are most efficient for gene transfer, as they contain an FRT site for Flp recombinase-mediated, site-directed integration of a single copy transgene. Therefore, the gene-of-interest can be introduced by DNA transfection without the need to select individual cell ... More
Human immunodeficiency virus type 1 envelope epitope-specific CD4(+) T lymphocytes in Simian/Human immunodeficiency virus-infected and vaccinated rhesus monkeys detected using a peptide-major histocompatibility complex class II tetramer
'A tetrameric recombinant major histocompatibility complex (MHC) class II-peptide complex was used to quantitate human immunodeficiency virus type 1 (HIV-1) envelope (Env)-specific CD4(+) T cells in vaccinated and in simian/human immunodeficiency virus (SHIV)-infected rhesus monkeys. A rhesus monkey MHC class II DR molecule, Mamu-DR*W201, and an HIV-1 Env peptide (p46) ... More
Human tumor-derived genomic DNA transduced into a recipient cell induces tumor-specific immune responses ex vivo.
'This article describes a DNA-based vaccination strategy evaluated ex vivo with human cells. The vaccine was prepared by transferring tumor-derived genomic DNA to PCI-13 cells, a highly immunogenic tumor cell line (' ... More
Protein-tyrosine phosphatase 1B is a negative regulator of insulin- and insulin-like growth factor-I-stimulated signaling.
Authors Kenner K A; Anyanwu E; Olefsky J M; Kusari J;
JournalJ Biol Chem
PubMed ID8702689
'To understand the physiological role of protein-tyrosine phosphatase 1B (PTPase 1B) in insulin and insulin-like growth factor-I (IGF-I) signaling, we established clonal cell lines overexpressing wild type or inactive mutant (C215S) PTPase 1B in cells overexpressing insulin (Hirc) or IGF-I (CIGFR) receptors. PTPase 1B overexpression in transfected cells was verified ... More
Suppression of Androgen Receptor Transactivation by Pyk2 via Interaction and Phosphorylation of the ARA55 Coregulator.
Authors Wang Xin; Yang Yue; Guo Xiaojian; Sampson Erik R; Hsu Cheng-Lung; Tsai Meng-Yin; Yeh Shuyuan; Wu Guan; Guo Yinglu; Chang Chawnshang;
JournalJ Biol Chem
PubMed ID11856738
'The proline-rich tyrosine kinase 2 (Pyk2) was first identified as a key kinase linked to the MAP kinase and JNK signaling pathways that play important roles in cell growth and adhesion. The linkage between Pyk2 and the androgen receptor (AR), an important transcription factor in prostate cancer progression, however, remains ... More
A TRP Channel that Senses Cold Stimuli and Menthol.
Authors Peier Andrea M; Moqrich Aziz; Hergarden Anne C; Reeve Alison J; Andersson David A; Story Gina M; Earley Taryn J; Dragoni Ilaria; McIntyre Peter; Bevan Stuart; Patapoutian Ardem;
JournalCell
PubMed ID11893340
'A distinct subset of sensory neurons are thought to directly sense changes in thermal energy through their termini in the skin. Very little is known about the molecules that mediate thermoreception by these neurons. Vanilloid Receptor 1 (VR1), a member of the TRP family of channels, is activated by noxious ... 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
MADR2 maps to 18q21 and encodes a TGFbeta-regulated MAD-related protein that is functionally mutated in colorectal carcinoma.
Authors Eppert K; Scherer S W; Ozcelik H; Pirone R; Hoodless P; Kim H; Tsui L C; Bapat B; Gallinger S; Andrulis I L; Thomsen G H; Wrana J L; Attisano L;
JournalCell
PubMed ID8752209
The MAD-related (MADR) family of proteins are essential components in the signaling pathways of serine/threonine kinase receptors for the transforming growth factor beta (TGFbeta) superfamily. We demonstrate that MADR2 is specifically regulated by TGFbeta and not bone morphogenetic proteins. The gene for MADR2 was found to reside on chromosome 18q21, ... More
Tyrosine sulfation of the amino terminus of CCR5 facilitates HIV-1 entry.
AuthorsFarzan M, Mirzabekov T, Kolchinsky P, Wyatt R, Cayabyab M, Gerard NP, Gerard C, Sodroski J, Choe H
JournalCell
PubMed ID10089882
Chemokine receptors and related seven-transmembrane-segment (7TMS) receptors serve as coreceptors for entry of human and simian immunodeficiency viruses (HIV-1, HIV-2, and SIV) into target cells. Each of these otherwise diverse coreceptors contains an N-terminal region that is acidic and tyrosine rich. Here, we show that the chemokine receptor CCR5, a ... 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
Human immunodeficiency virus type 1 Vpr-dependent cell cycle arrest through a mitogen-activated protein kinase signal transduction pathway.
AuthorsYoshizuka N, Yoshizuka-Chadani Y, Krishnan V, Zeichner SL,
JournalJ Virol
PubMed ID16103188
The human immunodeficiency virus type 1 (HIV-1) Vpr protein has important functions in advancing HIV pathogenesis via several effects on the host cell. Vpr mediates nuclear import of the preintegration complex, induces host cell apoptosis, and inhibits cell cycle progression at G(2), which increases HIV gene expression. Some of Vpr's ... 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
AuthorsXia ZB, Popovic R, Chen J, Theisler C, Stuart T, Santillan DA, Erfurth F, Diaz MO, Zeleznik-Le NJ,
JournalProc Natl Acad Sci U S A
PubMed ID16169901
MLL, involved in many chromosomal translocations associated with acute myeloid and lymphoid leukemia, has >50 known partner genes with which it is able to form in-frame fusions. Characterizing important downstream target genes of MLL and of MLL fusion proteins may provide rational therapeutic strategies for the treatment of MLL-associated leukemia. ... More
Mevalonate kinase is a cytosolic enzyme in humans.
In the past decade several reports have appeared which suggest that peroxisomes play a central role in isoprenoid/cholesterol biosynthesis. These suggestions were based primarily on the reported finding of several of the enzymes of the presqualene segment of the biosynthetic pathway in peroxisomes. More recently, however, conflicting results have been ... More
T-cell factor 4N (TCF-4N), a novel isoform of mouse TCF-4, synergizes with beta-catenin to coactivate C/EBPalpha and steroidogenic factor 1 transcription factors.
We have cloned T-cell factor 4N (TCF-4N), an alternative isoform of TCF-4, from developing pituitary and 3T3-L1 preadipocytes. This protein contains the N-terminal interaction domain for beta-catenin but lacks the DNA binding domain. While TCF-4N inhibited coactivation by beta-catenin of a TCF/lymphoid-enhancing factor (LEF)-dependent promoter, TCF-4N potentiated coactivation by beta-catenin ... More
The opioid system modulates several physiological processes, including analgesia, the stress response, the immune response and neuroendocrine function. Pharmacological and molecular cloning studies have identified three opioid-receptor types, delta, kappa and mu, that mediate these diverse effects. Little is known about the ability of the receptors to interact to form ... More
Envelope variants from women recently infected with clade A human immunodeficiency virus type 1 confer distinct phenotypes that are discerned by competition and neutralization experiments.
AuthorsPainter SL, Biek R, Holley DC, Poss M,
JournalJ Virol
PubMed ID12857914
Women infected with clade A human immunodeficiency virus type 1 harbor a virus population that is genetically diverse in the envelope gene, a fact that contrasts with the homogeneous virus population identified in newly infected men. It is not known whether viral genetic diversity at this early stage of infection ... More
Distinct functional properties of Rab3A and Rab3B in PC12 neuroendocrine cells.
AuthorsWeber E, Jilling T, Kirk KL
JournalJ Biol Chem
PubMed ID8636125
Rab3A and Rab3B are highly homologous monomeric GTPases that are putative regulators of exocytosis in those tissues in which they are expressed. We have characterized and directly compared the targeting and functional properties of these isoforms in PC12 neuroendocrine cells. Rab3A and Rab3B both targeted to norepinephrine (NE)-containing large dense ... More
Modulation of estrogen receptor-mediated transactivation by orphan receptor TR4 in MCF-7 cells.
Authors Shyr Chih-Rong; Hu Yueh-Chiang; Kim Eungseok; Chang Chawnshang;
JournalJ Biol Chem
PubMed ID11844790
The human testicular orphan receptor 4 (TR4) is a member of the nuclear receptor superfamily that shows a broad tissue distribution with higher expression in the nervous system and male reproductive tract. TR4 functions as a transcriptional modulator that controls various target genes via binding to the DNA hormone response ... More
Wortmannin-sensitive activation of p70s6k by endogenous and heterologously expressed Gi-coupled receptors.
Authors Wilson M; Burt A R; Milligan G; Anderson N G;
JournalJ Biol Chem
PubMed ID8621477
In order to study the regulation of the ribosomal protein S6 kinase, p70s6k, by G protein-coupled receptors, Rat-1 fibroblasts were stably transfected with two versions of the alpha2 adrenergic receptor. Stimulation of clone 1C cells, which express 3.5 pmol/mg of protein of the human alpha2C10 receptor, with the alpha2 agonist ... More
Role of JunB in erythroid differentiation.
Authors Jacobs-Helber Sarah M; Abutin Randolph M; Tian Cuixia; Bondurant Maurice; Wickrema Amittha; Sawyer Stephen T;
JournalJ Biol Chem
PubMed ID11726656
The role of junB as a regulator of erythroid cell survival, proliferation, and differentiation was tested by controlled expression of JunB in the erythropoietin (EPO)-dependent erythroleukemia cell line HCD57. JunB induced erythroid differentiation as evidenced by increased expression of the erythroid-specific proteins beta-globin, spectrin-alpha, and TER-119. Expression of JunB for ... More
Matrix metalloproteinase 2 (gelatinase A) regulates glomerular mesangial cell proliferation and differentiation.
Authors Turck J; Pollock A S; Lee L K; Marti H P; Lovett D H;
JournalJ Biol Chem
PubMed ID8663054
A biologic role for the 72-kDa gelatinase A (matrix metalloproteinase 2; MMP-2), beyond simple extracellular matrix turnover, was evaluated in glomerular mesangial cells. To determine the significance of MMP-2 secretion for the acquisition of the inflammatory phenotype, we reduced the constitutive secretion of MMP-2 by cultured mesangial cells with antisense ... More
Optimization of tetracycline-responsive recombinant protein production and effect on cell growth and ER stress in mammalian cells.
The inducible T-REx system and other inducible expression systems have been developed in order to control the expression levels of recombinant protein in mammalian cells. In order to study the effects of heterologous protein expression on mammalian host behavior, the gene for recombinant Human transferrin (hTf) was integrated into HEK-293 ... More
Differential effects of membrane sphingomyelin and cholesterol on agonist-induced bitter taste receptor T2R14 signaling.
AuthorsShaik FA, Chelikani P
JournalMol Cell Biochem
PubMed ID31541354
'Membrane lipids regulate the structure and function of G protein-coupled receptors (GPCRs). Previously we have shown that membrane cholesterol regulates the signaling of two human bitter taste receptors (T2Rs), T2R4 and T2R14. Another major plasma membrane lipid known to influence the function of membrane proteins including GPCRs is sphingomyelin. The ... More
Quantitative interaction proteomics reveals differences in the interactomes of amyloid precursor protein isoforms.
AuthorsAndrew RJ, Fisher K, Heesom KJ, Kellett KAB, Hooper NM
JournalJ Neurochem
PubMed ID30664241
'The generation of the amyloid-ß (Aß) peptides from the amyloid precursor protein (APP) through sequential proteolysis by ß- and ?-secretases is a key pathological event in the initiation and propagation of Alzheimer''s disease. Aß and the transcriptionally active APP intracellular domain are generated preferentially from the APP695 isoform compared to ... More
TRIM32, but not its muscular dystrophy-associated mutant, positively regulates and is targeted to autophagic degradation by p62/SQSTM1.
AuthorsOverå KS, Garcia-Garcia J, Bhujabal Z, Jain A, Øvervatn A, Larsen KB, Deretic V, Johansen T, Lamark T, Sjøttem E
JournalJ Cell Sci
PubMed ID31685529
'The tripartite motif (TRIM) proteins constitute a family of ubiquitin E3 ligases involved in a multitude of cellular processes, including protein homeostasis and autophagy. TRIM32 is characterized by six protein-protein interaction domains termed NHL, various point mutations in which are associated with limb-girdle-muscular dystrophy 2H (LGMD2H). Here, we show that ... More
The anthelmintic praziquantel is a human serotoninergic G-protein-coupled receptor ligand.
'Schistosomiasis is a debilitating tropical disease caused by infection with parasitic blood flukes. Approximately 260 million people are infected worldwide, underscoring the clinical and socioeconomic impact of this chronic infection. Schistosomiasis is treated with the drug praziquantel (PZQ), which has proved the therapeutic mainstay for over three decades of clinical ... More
Regulatory mechanisms of incomplete huntingtin mRNA splicing.
AuthorsNeueder A, Dumas AA, Benjamin AC, Bates GP
JournalNat Commun
PubMed ID30262848
'Huntington''s disease is caused by a CAG repeat expansion in exon 1 of the HTT gene. We have previously shown that exon 1 HTT does not always splice to exon 2 producing a small transcript (HTTexon1) that encodes the highly pathogenic exon 1 HTT protein. The mechanisms by which this ... More
Controversial Effects of D-Amino Acid Oxidase Activator (DAOA)/G72 on D-Amino Acid Oxidase (DAO) Activity in Human Neuronal, Astrocyte and Kidney Cell Lines: The N-methyl D-aspartate (NMDA) Receptor Hypofunction Point of View.
AuthorsJagannath V, Brotzakis ZF, Parrinello M, Walitza S, Grünblatt E
JournalFront Mol Neurosci
PubMed ID29114206
Dysfunction of D-amino acid oxidase (
Erratum: Genome-scale activation screen identifies a lncRNA locus regulating a gene neighbourhood.
This corrects the article DOI: 10.1038/nature23451.
Inhibition of double-stranded RNA-dependent protein kinase prevents oxytosis and ferroptosis in mouse hippocampal HT22 cells.
AuthorsHirata Y, Iwasaki T, Makimura Y, Okajima S, Oh-Hashi K, Takemori H
JournalToxicology
PubMed ID30817950
Double-stranded RNA-dependent protein kinase (PKR) is a component of signal transduction pathways mediating various stress signals including oxidative stress and endoplasmic reticulum (ER) stress and is suggested to be implicated in several neurodegenerative diseases. Cell death in neurodegenerative conditions has been linked to oxidative stress; however, the involvement of PKR ... More
BRAF Targeting Sensitizes Resistant Melanoma to Cytotoxic T Cells.
AuthorsAtay C, Kwak T, Lavilla-Alonso S, Donthireddy L, Richards A, Moberg V, Pilon-Thomas S, Schell M, Messina JL, Rebecca VW, Xiao M, Tan J, Zhang G, Weber JS, Herlyn M, Sarnaik AA, Gabrilovich DI
JournalClin Cancer Res
PubMed ID30765391
BRAF and MEK inhibitors (BRAFi and MEKi) are actively used for the treatment of metastatic melanoma in patients with BRAF
The intraflagellar transport protein IFT20 controls lysosome biogenesis by regulating the post-Golgi transport of acid hydrolases.
AuthorsFinetti F, Cassioli C, Cianfanelli V, Onnis A, Paccagnini E, Kabanova A, Baldari CT
JournalCell Death Differ
PubMed ID31142807
The assembly and function of the primary cilium depends on multimolecular intraflagellar transport (IFT) complexes that shuttle their cargo along the axonemal microtubules through their interaction with molecular motors. The IFT system has been moreover recently implicated in a reciprocal interplay between autophagy and ciliogenesis. We have previously reported that ... More