Browse
Submit Data
Databases
API
Help

Dataset Information

26 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CCN5, a novel transcriptional repressor

ABSTRACT: CCN5 is a member of the CCN (Connective Tissue Growth Factor/Cysteine-rich 61/Nephroblastoma overexpressed) family and was identified as an estrogen-inducible gene in estrogen receptor-positive cell lines. However, the role of CCN5 in breast carcinogenesis remains unclear. We report here that CCN5 protein is localized mostly in the cytoplasm, and in part in the nucleus, of human tumor breast tissue. Using a heterologous transcription assay, we demonstrate that CCN5 can act as a transcriptional repressor, presumably through association with histone deacetylase HDAC1. Microarray gene expression analysis showed that CCN5 represses expression of genes associated with epithelial-mesenchymal transition (EMT) as well as expression of key components of the TGF-beta signaling pathway, prominent among them TGF-betaRII receptor. We show that CCN5 is recruited to the TGF-betaRII promoter, thereby providing a mechanism by which CCN5 restricts transcription of the TGF-betaRII gene. Consistent with this finding, we found that CCN5 functions to suppress TGF-beta-induced transcriptional responses and invasion that is concomitant with EMT. Thus, our data uncovered CCN5 as a novel transcriptional repressor that plays an important role in regulating tumor progression functioning, at least in part, by inhibiting the expression of genes involved in the TGF-beta signaling cascade that is known to promote EMT. We performed microarray gene expression profiling of one MCF-7-sh-CCN5 sample and one MCF-7-sh-scrambled sample (control sample).

ORGANISM(S): Homo sapiens

SUBMITTER: SABBAH Michèle

PROVIDER: S-ECPF-GEOD-25431 | biostudies-other |

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

CCN5, a novel transcriptional repressor

Project description:CCN5 is a member of the CCN (Connective Tissue Growth Factor/Cysteine-rich 61/Nephroblastoma overexpressed) family and was identified as an estrogen-inducible gene in estrogen receptor-positive cell lines. However, the role of CCN5 in breast carcinogenesis remains unclear. We report here that CCN5 protein is localized mostly in the cytoplasm, and in part in the nucleus, of human tumor breast tissue. Using a heterologous transcription assay, we demonstrate that CCN5 can act as a transcriptional repressor, presumably through association with histone deacetylase HDAC1. Microarray gene expression analysis showed that CCN5 represses expression of genes associated with epithelial-mesenchymal transition (EMT) as well as expression of key components of the TGF-beta signaling pathway, prominent among them TGF-betaRII receptor. We show that CCN5 is recruited to the TGF-betaRII promoter, thereby providing a mechanism by which CCN5 restricts transcription of the TGF-betaRII gene. Consistent with this finding, we found that CCN5 functions to suppress TGF-beta-induced transcriptional responses and invasion that is concomitant with EMT. Thus, our data uncovered CCN5 as a novel transcriptional repressor that plays an important role in regulating tumor progression functioning, at least in part, by inhibiting the expression of genes involved in the TGF-beta signaling cascade that is known to promote EMT.

2011-11-30 | GSE25431 | GEO

CCN5, a novel transcriptional repressor

2011-11-30 | E-GEOD-25431 | biostudies-arrayexpress

CCN5, a novel transcriptional repressor of the transforming growth factor ? signaling pathway.

Project description:CCN5 is a member of the CCN (connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed) family and was identified as an estrogen-inducible gene in estrogen receptor-positive cell lines. However, the role of CCN5 in breast carcinogenesis remains unclear. We report here that the CCN5 protein is localized mostly in the cytoplasm and in part in the nucleus of human tumor breast tissue. Using a heterologous transcription assay, we demonstrate that CCN5 can act as a transcriptional repressor presumably through association with histone deacetylase 1 (HDAC1). Microarray gene expression analysis showed that CCN5 represses expression of genes associated with epithelial-mesenchymal transition (EMT) as well as expression of key components of the transforming growth factor ? (TGF-?) signaling pathway, prominent among them TGF-?RII receptor. We show that CCN5 is recruited to the TGF-?RII promoter, thereby providing a mechanism by which CCN5 restricts transcription of the TGF-?RII gene. Consistent with this finding, CCN5, we found, functions to suppress TGF-?-induced transcriptional responses and invasion that is concomitant with EMT. Thus, our data uncovered CCN5 as a novel transcriptional repressor that plays an important role in regulating tumor progression functioning, at least in part, by inhibiting the expression of genes involved in the TGF-? signaling cascade that is known to promote EMT.

| S-EPMC3135290 | biostudies-literature

HACE1: A novel repressor of RAR transcriptional activity.

Project description:The diverse biological actions of retinoic acid (RA) are mediated by RA receptors (RARs) and retinoid X receptors (RXRs). While the coregulatory proteins that interact with the ligand-dependent AF-2 in the E region are well studied, the ligand-independent N-terminal AF-1 domain-interacting partners and their influence(s) on the function of RARs are poorly understood. HECT domain and Ankyrin repeat containing E3 ubiquitin-protein ligase (HACE1) was isolated as a RARbeta(3) AB region interacting protein. HACE1 interacts with RARbeta(3) both in in vitro GST pull-down and in cell-based coprecipitation assays. The interaction sites map to the N terminus of RARbeta(3) and the C terminus of HACE1. HACE1 functionally represses the transcriptional activity of RARalpha(1), RARbeta isoforms 1, 2, and 3, but not RARgamma(1) in luciferase reporter assays. In addition, HACE1 represses the endogenous RAR-regulated genes CRABP II, RIG1 and RARbeta(2), but not RAI3 in CAOV3 cells. Mutation of the putative catalytic cysteine (C876 of LF HACE1), which is indispensable for its E3 ubiquitin ligase activity, does not alter the repressive effect of HACE1 on the transcriptional activity of RARbeta(3). On the other hand, HACE1 inhibits the RA dependent degradation of RARbeta(3). It is possible that the repression of RAR-regulated transcription by HACE1 is due to its ability to inhibit the RA-dependent degradation of RARs.

| S-EPMC2736627 | biostudies-literature

A novel MAs(III)-selective ArsR transcriptional repressor.

Project description:Microbial expression of genes for resistance to heavy metals and metalloids is usually transcriptionally regulated by the toxic ions themselves. Arsenic is a ubiquitous, naturally occurring toxic metalloid widely distributed in soil and groundwater. Microbes biotransform both arsenate (As(V)) and arsenite (As(III)) into more toxic methylated metabolites methylarsenite (MAs(III)) and dimethylarsenite (DMAs(III)). Environmental arsenic is sensed by members of the ArsR/SmtB family. The arsR gene is autoregulated and is typically part of an operon that contains other ars genes involved in arsenic detoxification. To date every identified ArsR is regulated by inorganic As(III). Here we described a novel ArsR from Shewanella putrefaciens selective for MAs(III). SpArsR orthologs control expression of two MAs(III) resistance genes, arsP that encodes the ArsP MAs(III) efflux permease, and arsH encoding the ArsH MAs(III) oxidase. SpArsR has two conserved cysteine residues, Cys101 and Cys102. Mutation of either resulted in loss of MAs(III) binding, indicating that they form an MAs(III) binding site. SpArsR can be converted into an As(III)-responsive repressor by introduction of an additional cysteine that allows for three-coordinate As(III) binding. Our results indicate that SpArsR evolved selectivity for MAs(III) over As(III) in order to control expression of genes for MAs(III) detoxification.

| S-EPMC5653410 | biostudies-literature

BAZF, a novel Bcl6 homolog, functions as a transcriptional repressor.

Project description:The BCL6 gene, which has been identified from the chromosomal translocation breakpoint in B-cell lymphomas, functions as a sequence-specific transcriptional repressor. We cloned a novel Bcl6-homologous gene, BAZF (encoding Bcl6-associated zinc finger protein). The predicted amino acid sequence of BAZF indicated that the BTB/POZ domain and the five repeats of the Krüppel-like zinc finger motif are located in the NH2-terminal region and the COOH-terminal region, respectively. BAZF associated with Bcl6 at the BTB/POZ domain and localized in the nucleus. Since zinc finger motifs of BAZF were 94% identical to those of Bcl6 at the amino acid level, BAZF bound specifically to the DNA-binding sequence of Bcl6 and functioned as a transcriptional repressor. The repressor activity was associated with both the BTB/POZ domain and the middle portion of BAZF. The 17-amino-acid sequence in the middle portion was completely conserved between BAZF and Bcl6, and the conserved region was critical for the repressor activity. Expression of BAZF mRNA, like that of Bcl6 mRNA, was induced in activated lymphocytes as an immediate-early gene. Therefore, the biochemical character of BAZF is similar to that of Bcl6 although the tissue expression pattern of BAZF differs from that of Bcl6. This is apparently the first report of a gene family whose members encode zinc finger proteins with the BTB/POZ domain.

| S-EPMC109007 | biostudies-literature

The transcriptional repressor Glis2 is a novel binding partner for p120 catenin.

Project description:In epithelial cells, p120 catenin (p120) localizes at cell-cell contacts and regulates adhesive function of the cadherin complex. In addition, p120 has been reported to localize in the nucleus, although the nuclear function of p120 is not fully understood. Here, we report the identification of Gli-similar 2 (Glis2) as a novel binding protein for p120. Glis2 is a Krüppel-like transcriptional repressor with homology to the Gli family, but its physiological function has not been well characterized. In this study, we show that coexpression of Glis2 and Src induces nuclear translocation of p120. Furthermore, p120 induces the C-terminal cleavage of Glis2, and this cleavage is further enhanced by Src. The cleaved form of Glis2 loses one of its five zinc finger domains, but it is still able to bind DNA. Functional studies in chick neural tube indicate that full-length Glis2 can affect neuronal differentiation, whereas the cleaved form requires coexpression of p120 to have a similar effect. These data indicate that p120 has additional novel functions in the nucleus together with Glis2.

| S-EPMC1855037 | biostudies-literature

NIR is a novel INHAT repressor that modulates the transcriptional activity of p53.

Project description:Most transcriptional repression pathways depend on the targeted deacetylation of histone tails. In this report, we characterize NIR, a novel transcriptional corepressor with inhibitor of histone acetyltransferase (INHAT) activity. NIR (Novel INHAT Repressor) is ubiquitously expressed throughout embryonic development and adulthood. NIR is a potent transcriptional corepressor that is not blocked by histone deacetylase inhibitors and is capable of silencing both basal and activator-driven transcription. NIR directly binds to nucleosomes and core histones and prevents acetylation by histone acetyltransferases, thus acting as a bona fide INHAT. Using a tandem affinity purification approach, we identified the tumor suppressor p53 as a NIR-interacting partner. Association of p53 and NIR was verified in vitro and in vivo. Upon recruitment by p53, NIR represses transcription of both p53-dependent reporters and endogenous target genes. Knock-down of NIR by RNA interference significantly enhances histone acetylation at p53-regulated promoters. Moreover, p53-dependent apoptosis is robustly increased upon depletion of NIR. In summary, our findings describe NIR as a novel INHAT that plays an important role in the control of p53 function.

| S-EPMC1315397 | biostudies-literature

A Novel Function of δ Factor from Bacillus subtilis as a Transcriptional Repressor.

Project description:δ, a small protein found in most Gram-positive bacteria was, for a long time, thought to be a subunit of RNA polymerase (RNAP) and was shown to be involved in recycling of RNAP at the end of each round of transcription. However, how δ participates in both up-regulation and down-regulation of genes in vivo remains unclear. We have recently shown, in addition to the recycling of RNAP, δ functions as a transcriptional activator by binding to an A-rich sequence located immediately upstream of the -35 element, consequently facilitating the open complex formation. The result had explained the mechanism of up-regulation of the genes by δ. Here, we show that Bacillus subtilis δ could also function as a transcriptional repressor. Our results demonstrate that δ binds to an A-rich sequence located near the -35 element of the spo0B promoter, the gene involved in the regulatory cascade of bacterial sporulation and inhibits the open complex formation due to steric clash with σ region 4.2. We observed a significant increase in the mRNA level of the spo0B gene in a δ-knock-out strain of B. subtilis compared with the wild-type. Thus, the results report a novel function of δ, and suggest the mechanism of down-regulation of genes in vivo by the protein.

| S-EPMC5104928 | biostudies-literature

The transcriptional repressor gene Mad3 is a novel target for regulation by E2F1.

Project description:Mad family proteins are transcriptional repressors that antagonize the activity of the c- Myc proto-oncogene product. Mad3 is expressed specifically during the S-phase of the cell cycle in both proliferating and differentiating cells, suggesting that its biological function is probably linked to processes that occur during this period. To determine the mechanisms that regulate the cell-cycle-specific transcription of Mad3, we used reporter gene assays in stably transfected fibroblasts. We show that the activation of Mad3 at the G1-S boundary is mediated by a single E2F (E2 promoter binding factor)-binding site within the 5'-flanking region of the gene. Mutation of this element eliminated transcriptional activation at S-phase, suggesting that the positively acting E2F proteins play a role in Mad3 regulation. Using electrophoretic mobility-shift assays and chromatin immunoprecipitation, we show that E2F1 binds to the Mad3 5'-flanking region both in vitro and in vivo. We thus identify Mad3 as a novel transcriptional target of E2F1.

| S-EPMC1223166 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data