Abstract:
:Hepatocyte growth factor (HGF), a cytokine with multiple functions, exhibits cell-type-specific as well as cytokine- and steroid hormone-regulated expression. The HGF gene is known to be expressed predominately in mesenchymal but not in epithelial cells. In this study, we report the identification of a cell-type-specific transcriptional repressor in the promoter region of the mouse HGF gene, which is evidently responsible for the suppression of HGF expression in epithelial cells. Gel mobility shift assays and DNase I footprinting studies revealed that a 27-bp element (-16 to +11) around the transcription initiation site is responsible for the binding of a nuclear protein which is present in epithelial but not in mesenchymally derived cells. Further analysis of the binding activity of the DNA region with nuclear protein revealed that an approximately 19-bp sequence containing a unique palindromic structure (5'-AACCGACCGGTT-3') overlapped by a CAP box is essential for binding. Substitution of a single base (the contact site) within this region by site-directed mutagenesis resulted in total abrogation of the binding of the nuclear protein and a concomitant increase in the transcriptional activity of various lengths of HGF-chloramphenicol acetyltransferase fused genes when transfected into the epithelial cell line RL95-2 but not the mesenchymal cell line NIH 3T3. Southwestern (DNA-protein) analyses revealed that the nuclear protein which binds to this repressor element is a single polypeptide of approximately 70 kDa. Analysis of the nuclear extract prepared from regenerating mouse liver at various times after two-thirds partial hepatectomy by gel mobility shift assay revealed a substantial reduction (more than 75% within 3 h) in the binding of the repressor to its cognate binding site. Our results suggest that a cis-acting transcriptional repressor in the promoter region of the mouse HGF gene is involved in cell-type-specific regulation through binding to its cognate trans-acting protein which exists in epithelial cells but is absent in fibroblast cells.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Liu Y,Beedle AB,Lin L,Bell AW,Zarnegar Rdoi
10.1128/mcb.14.11.7046subject
Has Abstractpub_date
1994-11-01 00:00:00pages
7046-58issue
11eissn
0270-7306issn
1098-5549journal_volume
14pub_type
杂志文章abstract::Recently, we demonstrated that the microRNA 424(322)/503 [miR-424(322)/503] cluster is transcriptionally controlled by transforming growth factor β (TGF-β) in the mammary epithelium. Induction of this microRNA cluster impacts mammary epithelium fate by regulating apoptosis and insulin-like growth factor 1 (IGF1) signa...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00611-14
更新日期:2014-12-01 00:00:00
abstract::In eukaryotes, crossovers in mitotic cells can have deleterious consequences and therefore must be suppressed. Mutations in BLM give rise to Bloom syndrome, a disease that is characterized by an elevated rate of crossovers and increased cancer susceptibility. However, simple eukaryotes such as Saccharomyces cerevisiae...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.9.3431-3442.2005
更新日期:2005-05-01 00:00:00
abstract::Heteroduplexes formed between DNA strands derived from different homologous chromosomes are an intermediate in meiotic crossing over in the yeast Saccharomyces cerevisiae and other eucaryotes. A heteroduplex formed between wild-type and mutant genes will contain a base pair mismatch; failure to repair this mismatch wi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.2.737
更新日期:1991-02-01 00:00:00
abstract::The relationship between chromatin remodeling and histone acetylation at the yeast CUP1 gene was addressed. CUP1 encodes a metallothionein required for cell growth at high copper concentrations. Induction of CUP1 with copper resulted in targeted acetylation of both H3 and H4 at the CUP1 promoter. Nucleosomes containin...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.18.6406-6416.2002
更新日期:2002-09-01 00:00:00
abstract::Ribosomal (r) proteins encoded by polyadenylated RNA were specifically precipitated in vitro from polysomes by using antibodies raised against characterized Drosophila melanogaster r proteins. The immuno-purified mRNA in the polysome complex was used to prepare cDNA with which to probe a D. melanogaster genomic librar...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.12.2643
更新日期:1984-12-01 00:00:00
abstract::2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other aryl hydrocarbon receptor (AhR) ligands suppress 17beta-estradiol (E)-induced responses in the rodent uterus and mammary tumors and in human breast cancer cells. Treatment of ZR-75, T47D, and MCF-7 human breast cancer cells with TCDD induces proteasome-dependent deg...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.6.1843-1855.2003
更新日期:2003-03-01 00:00:00
abstract::The human ERCC3 gene, which corrects specifically the nucleotide excision repair defect in human xeroderma pigmentosum group B and cross-complements the repair deficiency in rodent UV-sensitive mutants of group 3, encodes a presumed DNA helicase that is identical to the p89 subunit of the general transcription factor ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.6.4126
更新日期:1994-06-01 00:00:00
abstract::Translocation of preproteins across the mitochondrial outer membrane is mediated by the TOM complex. This complex consists of receptor components for the initial contact with preproteins at the mitochondrial surface and membrane-embedded proteins which promote transport and form the translocation pore. In order to und...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.9.5256
更新日期:1998-09-01 00:00:00
abstract::Retinoblastoma (RB) tumors develop when both alleles of a gene (RB1) are mutated and unable to function normally. Recently, Friend et al. [S. H. Friend, R. Bernards, S. Rogelj, R. A. Weinberg, J. M. Rapaport, D. M. Albert, and T. P. Dryja, Nature (London) 32:643-646, 1986] reported the cloning of a gene, 4.7R, with so...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.5.2082
更新日期:1988-05-01 00:00:00
abstract::The four receptor tyrosine kinases of the ErbB family play essential roles in several physiological processes and have also been implicated in tumor generation and/or progression. Activation of ErbB1/EGFR is mainly triggered by epidermal growth factor (EGF) and other related ligands, while activation of ErbB2, ErbB3, ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.1.270-285.2002
更新日期:2002-01-01 00:00:00
abstract::mRNAs are monitored for errors in gene expression by RNA surveillance, in which mRNAs that cannot be fully translated are degraded by the nonsense-mediated mRNA decay pathway (NMD). RNA surveillance ensures that potentially deleterious truncated proteins are seldom made. NMD pathways that promote surveillance have bee...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.10.6710
更新日期:1999-10-01 00:00:00
abstract::Recent studies have implicated the role of the SWI/SNF ATP-dependent chromatin remodeling complex in nuclear excision repair (NER), but the mechanism of its function has remained elusive. Here, we show that the human SWI/SNF component human SNF5 (hSNF5) interacts with UV damage recognition factor XPC and colocalizes w...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00503-09
更新日期:2009-12-01 00:00:00
abstract::3-Methyl adenine (3meA), a minor-groove DNA lesion, presents a strong block to synthesis by replicative DNA polymerases (Pols). To elucidate the means by which replication through this DNA lesion is mediated in eukaryotic cells, here we carry out genetic studies in the yeast Saccharomyces cerevisiae treated with the a...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01079-07
更新日期:2007-10-01 00:00:00
abstract::The RNA polymerase III transcription initiation factor TFIIIB contains the TATA-box-binding protein (TBP) and polymerase III-specific TBP-associated factors (TAFs). Previous studies have shown that DNA oligonucleotides containing the consensus TATA-box sequence inhibit polymerase III transcription, implying that the D...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.9.4639
更新日期:1996-09-01 00:00:00
abstract::We report in vivo analysis of histone and RNA polymerase II (pol II) occupancy at the 601 element, which functions as a strong in vitro nucleosome-positioning element and transcriptional pause site. Surprisingly, nucleosomes were not strongly positioned over the 601 element inserted either within a yeast chromosomal o...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.05599-11
更新日期:2011-08-01 00:00:00
abstract::F9 embryonic teratocarcinoma stem cells differentiate into an epithelial cell type called extraembryonic endoderm when treated with retinoic acid (RA), a derivative of retinol (vitamin A). This differentiation is presumably mediated through the actions of retinoid receptors, the RARs and RXRs. To delineate the functio...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.2.843
更新日期:1995-02-01 00:00:00
abstract::Chromatin is regulated by cross talk among different histone modifications, which can occur between residues within the same tail or different tails in the nucleosome. The latter is referred to as trans-tail regulation, and the best-characterized example of this is the dependence of H3 methylation on H2B ubiquitylatio...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00324-10
更新日期:2010-07-01 00:00:00
abstract::In the absence of telomerase, telomeres erode, provoking accumulation of DNA damage and death by senescence. Rare survivors arise, however, due to Rad52-based amplification of telomeric sequences by homologous recombination. The present study reveals that in budding yeast cells, postsenescence survival relying on ampl...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00817-08
更新日期:2009-02-01 00:00:00
abstract::The degradation of many proteins involves the sequential ligation of ubiquitin molecules to the substrate to form a multiubiquitin chain linked through Lys-48 of ubiquitin. To test for the existence of alternate forms of multiubiquitin chains, we examined the effects of individually substituting each of six other Lys ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.3.1265
更新日期:1995-03-01 00:00:00
abstract::The baker's yeast Saccharomyces cerevisiae expresses three homologues of the Nramp family of metal transporters: Smf1p, Smf2p, and Smf3p, encoded by SMF1, SMF2, and SMF3, respectively. Here we report a comparative analysis of the yeast Smf proteins at the levels of localization, regulation, and function of the corresp...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.21.7893-7902.2000
更新日期:2000-11-01 00:00:00
abstract::Tax corresponds to a 40-kDa transforming protein from the pathogenic retrovirus human T-cell leukemia virus type 1 (HTLV-1) that activates nuclear expression of the NF-kappaB/Rel family of transcription factors by an unknown mechanism. Tax expression promotes N-terminal phosphorylation and degradation of IkappaB alpha...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.9.5157
更新日期:1998-09-01 00:00:00
abstract::Much of our knowledge on adipogenesis comes from cell culture models of preadipocyte differentiation. Adipogenesis is induced by treating confluent preadipocytes with the adipogenic cocktail, which activates transcription factors (TFs) glucocorticoid receptor (GR) and CREB within minutes and increases expression of TF...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00554-16
更新日期:2017-01-04 00:00:00
abstract::To interrogate endogenous p21(WAF1/CIP1) (p21) promoter activity under basal conditions and in response to various forms of stress, knock-in imaging reporter mice in which expression of firefly luciferase (FLuc) was placed under the control of the endogenous p21 promoter within the Cdkn1a gene locus were generated. Bi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.05243-11
更新日期:2011-09-01 00:00:00
abstract::Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder resulting from the neoplastic transformation of a hematopoietic stem cell. The majority of cases of CML are associated with the (9;22) chromosome translocation that generates the bcr-abl chimeric gene. Alpha interferon (IFN-alpha) treatment ind...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.4.1149-1161.2000
更新日期:2000-02-01 00:00:00
abstract::We have examined the ability of the simian virus 40 72-base pair enhancer segment to simultaneously activate multiple transcription units with plasmids that contain one, two, or three simian virus 40-based transcription units in various arrangements. After transfection into CV1 cells, the expression of a marker gene, ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.7.2593
更新日期:1986-07-01 00:00:00
abstract::TEL1 is important in Saccharomyces cerevisiae telomere maintenance, and its kinase activity is required. Tel1p associates with telomeres in vivo, is enriched at short telomeres, and enhances the binding of telomerase components to short telomeres. However, it is unclear how the kinase activity and telomere association...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01896-08
更新日期:2009-09-01 00:00:00
abstract::Sensory hair cells convert mechanical motion into chemical signals. Otoferlin, a six-C2 domain transmembrane protein linked to deafness in humans, is hypothesized to play a role in exocytosis at hair cell ribbon synapses. To date, however, otoferlin has been studied almost exclusively in mouse models, and no rescue ex...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01439-14
更新日期:2015-03-01 00:00:00
abstract::Thrombospondins are a family of stress-inducible secreted glycoproteins that underlie tissue remodeling. We recently reported that thrombospondin-4 (Thbs4) has a critical intracellular function, regulating the adaptive endoplasmic reticulum (ER) stress pathway through activating transcription factor 6α (Atf6α). In the...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00607-15
更新日期:2015-10-12 00:00:00
abstract::DHTKD1, a part of 2-ketoadipic acid dehydrogenase complex, is involved in lysine and tryptophan catabolism. Mutations in DHTKD1 block the metabolic pathway and cause 2-aminoadipic and 2-oxoadipic aciduria (AMOXAD), an autosomal recessive inborn metabolic disorder. In addition, a nonsense mutation in DHTKD1 that we ide...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00085-18
更新日期:2018-06-14 00:00:00
abstract::The regulation of a thyroid hormone-responsive gene in rats, designated spot 14, was explored. The expression of this gene in liver is rapidly (less than 10 min) and markedly (greater than 10-fold) altered by the administration of 3,5,3'-triiodo-L-thyronine (T3) to hypothyroid rats (P. Narayan, C. W. Liaw, and H. C. T...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.10.2642
更新日期:1985-10-01 00:00:00