Suppression of Ras-mediated tumorigenicity and metastasis through inhibition of the Met receptor tyrosine kinase.
Authors Furge K A; Kiewlich D; Le P; Vo M N; Faure M; Howlett A R; Lipson K E; Woude G F; Webb C P;
JournalProc Natl Acad Sci U S A
PubMed ID11535809
'Mutations in the Ras family of GTP binding proteins represent one of the most frequently observed genetic alterations in human cancers. We and others have recently demonstrated that expression of Met, the tyrosine kinase receptor for hepatocyte growth factor/scatter factor (HGF/SF), is significantly up-regulated in Ras-transformed cells. Because HGF/SF-Met signaling ... More
Structural basis of G protein specificity of human endothelin receptors. A study with endothelinA/B chimeras.
'The endothelin (ET) family of peptides acts via two subtypes of guanine nucleotide-binding regulatory protein (G protein)-coupled receptors termed ETA and ETB. ET-1 stimulated cAMP formation in Chinese hamster ovary (CHO) cells stably expressing human wild-type ETA (CHO/hETA cells) while it inhibited cAMP formation in CHO cells expressing human wild-type ... More
West Nile virus discriminates between DC-SIGN and DC-SIGNR for cellular attachment and infection.
'The C-type lectins DC-SIGN and DC-SIGNR bind mannose-rich glycans with high affinity. In vitro, cells expressing these attachment factors efficiently capture, and are infected by, a diverse array of appropriately glycosylated pathogens, including dengue virus. In this study, we investigated whether these lectins could enhance cellular infection by West Nile ... More
Presenilin 1 mutations activate gamma 42-secretase but reciprocally inhibit epsilon-secretase cleavage of amyloid precursor protein (APP) and S3-cleavage of notch.
Authors Chen Fusheng; Gu YongJun; Hasegawa Hiroshi; Ruan Xueying; Arawaka Shigeki; Fraser Paul; Westaway David; Mount Howard; St George-Hyslop Peter;
JournalJ Biol Chem
PubMed ID12119298
'The presenilin 1 (PS1) and presenilin 2 (PS2) proteins are necessary for proteolytic cleavage of the amyloid precursor protein (APP) within its transmembrane domain. One of these cleavage events (termed gamma-secretase) generates the C-terminal end of the Abeta-peptide by proteolysis near residue 710 or 712 of APP(770). Another event (termed ... 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
TRPM4 Is a Ca(2+)-Activated Nonselective Cation Channel Mediating Cell Membrane Depolarization.
Authors Launay Pierre; Fleig Andrea; Perraud Anne Laure; Scharenberg Andrew M; Penner Reinhold; Kinet Jean Pierre;
JournalCell
PubMed ID12015988
'Calcium-activated nonselective (CAN) cation channels are expressed in various excitable and nonexcitable cells supporting important cellular responses such as neuronal bursting activity, fluid secretion, and cardiac rhythmicity. We have cloned and characterized a second form of TRPM4, TRPM4b, a member of the TRP channel family, as a molecular candidate of ... More
Ectopic expression of necdin induces differentiation of mouse neuroblastoma cells.
'Necdin is expressed predominantly in postmitotic neurons, and ectopic expression of this protein strongly suppresses cell growth. Necdin has been implicated in the pathogenesis of Prader-Willi syndrome, a human neurodevelopmental disorder associated with genomic imprinting. Here we demonstrate that ectopic expression of necdin induces a neuronal phenotype in neuroblastoma cells. ... More
Retention of mutant low density lipoprotein receptor in ER leads to ER stress.
Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in the gene encoding the low density lipoprotein receptor (LDLR). More than 50% of these mutations lead to receptor proteins that are completely or partly retained in the endoplasmic reticulum (ER). The mechanisms involved in the intracellular processing and ... 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
Isolation of cell lines that show novel, murine leukemia virus-specific blocks to early steps of retroviral replication.
AuthorsBruce JW, Bradley KA, Ahlquist P, Young JA,
JournalJ Virol
PubMed ID16188999
In order to identify cellular proteins required for early stages of retroviral replication, a high volume screening with mammalian somatic cells was performed. Ten pools of chemically mutagenized Chinese hamster ovary (CHO-K1) cells were challenged with a murine leukemia virus (MLV) vector pseudotyped with the vesicular stomatitis virus glycoprotein (VSV-G), ... 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
DEF-1/ASAP1 is a GTPase-activating protein (GAP) for ARF1 that enhances cell motility through a GAP-dependent mechanism.
AuthorsFurman C, Short SM, Subramanian RR, Zetter BR, Roberts TM,
JournalJ Biol Chem
PubMed ID11773070
DEF-1/ASAP1 is an ADP-ribosylation factor GTPase-activating protein (ARF GAP) that localizes to focal adhesions and is involved in cytoskeletal regulation. In this paper, we use a cell-based ARF GAP assay to demonstrate that DEF-1 functions as a GAP for ARF1 and not ARF6 in vivo. This degree of substrate preference ... More
Astrocyte-specific Expression of the {alpha}1-Antichymotrypsin and Glial Fibrillary Acidic Protein Genes Requires Activator Protein-1.
AuthorsGopalan SM, Wilczynska KM, Konik BS, Bryan L, Kordula T,
JournalJ Biol Chem
PubMed ID16303762
An amyloid-associated serine proteinase inhibitor (serpin), alpha(1)-antichymotrypsin (ACT), is encoded by a gene located within the distal serpin subcluster on human chromosome 14q32.1. The expression of these distal serpin genes is determined by tissue-specific chromatin structures that allow their ubiquitous expression in hepatocytes; however, their expression is limited to a ... More
Tumor inhibition by genomically integrated inducible RNAi-cassettes.
AuthorsKappel S, Matthess Y, Zimmer B, Kaufmann M, Strebhardt K,
JournalNucleic Acids Res
PubMed ID16945954
RNA interference (RNAi) has emerged as a powerful tool to induce loss-of-function phenotypes by post-transcriptional silencing of gene expression. In this study we wondered whether inducible RNAi-cassettes integrated into cellular DNA possess the power to trigger neoplastic growth. For this purpose inducible RNAi vectors containing tetracycline (Tet)-responsive derivatives of the ... More
A set of independent selectable markers for transfection of the human malaria parasite Plasmodium falciparum.
AuthorsMamoun CB, Gluzman IY, Goyard S, Beverley SM, Goldberg DE
JournalProc Natl Acad Sci U S A
PubMed ID10411941
Genomic information is rapidly accumulating for the human malaria pathogen, Plasmodium falciparum. Our ability to perform genetic manipulations to understand Plasmodium gene function is limited. Dihydrofolate reductase is the only selectable marker presently available for transfection of P. falciparum. Additional markers are needed for complementation and for expression of mutated ... More
Forkhead family transcription factor FKHRL1 is expressed in human megakaryocytes. Regulation of cell cycling as a downstream molecule of thrombopoietin signaling.
AuthorsTanaka M, Kirito K, Kashii Y, Uchida M, Watanabe T, Endo H, Endoh T, Sawada K, Ozawa K, Komatsu N,
JournalJ Biol Chem
PubMed ID11278373
FKHRL1, a member of the Forkhead transcription factor family, is one of the downstream molecules of phosphatidylinositol 3-kinase-Akt. This molecule is a mammalian homolog of DAF-16, which plays an important role in the longevity of Caenorhabditis elegans. In this study we found that Akt and FKHRL1 proteins were detectable in ... More
Silencing of the mouse H-rev107 gene encoding a class II tumor suppressor by CpG methylation.
Authors Roder Karim; Latasa Maria-Jesus; Sul Hei Sook;
JournalJ Biol Chem
PubMed ID12055182
H-rev107 is a tumor suppressor originally isolated in revertants of H-ras-transformed cell lines. The gene is ubiquitously expressed in normal tissues but down-regulated in primary carcinomas or in many cell lines derived from tumors, including WEHI 7.1 lymphoma cells. Here, we show that unlike in H-rev107-expressing cells or tissues the ... More
The gamma -secretase-cleaved C-terminal fragment of amyloid precursor protein mediates signaling to the nucleus.
Authors Gao Y; Pimplikar S W;
JournalProc Natl Acad Sci U S A
PubMed ID11742091
Sequential processing of the amyloid precursor protein (APP) by beta- and gamma-secretases generates the Abeta peptide, a major constituent of the senile plaques observed in Alzheimer's disease. The cleavage by gamma-secretase also results in the cytoplasmic release of a 59- or 57-residue-long C-terminal fragment (Cgamma). This processing resembles regulated intramembrane ... More
Maturation of Lipoprotein Lipase in the Endoplasmic Reticulum. CONCURRENT FORMATION OF FUNCTIONAL DIMERS AND INACTIVE AGGREGATES.
Authors Ben-Zeev Osnat; Mao Hui Z; Doolittle Mark H;
JournalJ Biol Chem
PubMed ID11796709
The maturation of lipoprotein lipase (LPL) into a catalytically active enzyme was believed to occur only after its transport from the endoplasmic reticulum (ER) to the Golgi apparatus. To test this hypothesis, LPL located in these two subcellular compartments was separated and compared. Heparin affinity chromatography resolved low affinity, inactive ... More
The lymphocyte metalloprotease MDC-L (ADAM 28) is a ligand for the integrin alpha4beta1.
Authors Bridges Lance C; Tani Patricia H; Hanson Krista R; Roberts Charles M; Judkins Matthew B; Bowditch Ron D;
JournalJ Biol Chem
PubMed ID11724793
The interaction of lymphocytes with other cells is critical for normal immune surveillance and response. MDC-L (ADAM 28), a member of the ADAM (a disintegrin and metalloprotease) protein family, is expressed on the surface of human lymphocytes. ADAMs possess a disintegrin-like domain similar in sequence to small non-enzymatic snake venom ... More
Construction of a mavs-inactivated MDCK cell line for facilitating the propagation of canine distemper virus (CDV).
AuthorsCai C, Wang X, Zhao Y, Yi C, Jin Z, Zhang A, Han L
JournalMol Immunol
PubMed ID31352229
'Canine distemper is a highly contagious disease of wild and domestic carnivores. Obtaining of a suitable cell line for canine distemper virus (CDV) propagation is very important for field CDV isolation and vaccine antigen preparation. However, the cell line currently developed cell lines for CDV propagation are a marmoset lymphoid ... More
YAP-independent mechanotransduction drives breast cancer progression.
AuthorsLee JY, Chang JK, Dominguez AA, Lee HP, Nam S, Chang J, Varma S, Qi LS, West RB, Chaudhuri O
JournalNat Commun
PubMed ID31015465
Increased tissue stiffness is a driver of breast cancer progression. The transcriptional regulator YAP is considered a universal mechanotransducer, based largely on 2D culture studies. However, the role of YAP during in vivo breast cancer remains unclear. Here, we find that mechanotransduction occurs independently of YAP in breast cancer patient ... More
Krüppel-Like Factor 6 Is Required for Oxidative and Oncogene-Induced Cellular Senescence.
AuthorsSabatino ME, Castellaro A, Racca AC, Carbajosa González S, Pansa MF, Soria G, Bocco JL
JournalFront Cell Dev Biol
PubMed ID31824948
Krüppel-like factor 6 (KLF6) is a transcription factor involved in the regulation of several cellular processes. Regarding its role in tumorigenesis, KLF6 is considered a tumor suppressor. Numerous reports demonstrate its frequent genomic loss or down-regulation, implying a functional inactivation in a broad range of human cancers. Previous work from ... More
FBXW7 Triggers Degradation of KMT2D to Favor Growth of Diffuse Large B-cell Lymphoma Cells.
AuthorsSaffie R, Zhou N, Rolland D, Önder Ö, Basrur V, Campbell S, Wellen KE, Elenitoba-Johnson KSJ, Capell BC, Busino L
JournalCancer Res
PubMed ID32350066
Mature B-cell neoplasms are the fifth most common neoplasm. Due to significant heterogeneity at the clinical and genetic levels, current therapies for these cancers fail to provide long-term cures. The clinical success of proteasome inhibition for the treatment of multiple myeloma and B-cell lymphomas has made the ubiquitin pathway an ... More