Nuclear factor RIP140 modulates transcriptional activation by the estrogen receptor.

Cavaillès, Vincent; Dauvois, Sophie; L'Horset, F; Lopez, Gabriela N.; Hoare, Susan; Kushner, Peter J.; Parker, Malcolm G.

doi:10.1002/j.1460-2075.1995.tb00044.x

Cited by 707 publications

(517 citation statements)

References 65 publications

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“…Since this breast cancer cDNA encoded a nuclear receptor-binding auxiliary protein (Segars et al, 1993), we called the gene brx. Overlapping cDNA clones were consistent with a 5.3 kilobase cDNA encoding a 1428 amino acid protein with a 168 kilodalton predicted molecular mass distinct from proteins reported to bind nuclear hormone receptors (Cavailles et al, 1994(Cavailles et al, , 1995Halachmi et al, 1994;Jacq et al, 1994;Chen and Evans, 1995;Horlein et al, 1995;Onate et al, 1995;Le Douarin et al, 1995;Baniahmad et al, 1995).…”

Section: Identi®cation and Cloning Of Brx Cdnasupporting

confidence: 55%

“…An in vivo interaction between Brx and ER was suggested by a 2.5-fold enhancement of luciferase activity upon transfection of both constructs (Figure 4f). The magnitude of activation attributable to Brx ± ER interaction in the mammalian dual-hybrid system resembled published levels of activation for two NHR binding proteins; RIP 140 (Cavailles et al, 1995) and CBP/p300 (Sartorelli et al, 1997). The ability of the VP16DN3Brx construct to cause a slight increase in reporter activity was con®rmed by interaction of Brx protein with other general transcription factors (PHD, unpublished) and will be reported elsewhere.…”

Section: Brx Is Expressed In Reproductive and Immune Tissuessupporting

confidence: 55%

“…In addition, ligand was not required for in vitro binding of Brx to ER, and in fact the addition of estrogen (Figure 4e) and tamoxifen (not shown) only slightly augmented binding. A non-ligand dependent interaction has been noted for some NHR-binding proteins (Jacq et al, 1994), and in some in vitro studies (Cavailles et al, 1995). Two observations suggest that the mechanism by which Brx functions may involve association with unliganded ER in the cell.…”

Section: Discussionmentioning

confidence: 89%

“…For example, gene activation by nuclear hormone receptors (NHRs) has recently been shown to include additional proteins that associate directly with receptors, including the estrogen receptor (see : Horwitz et al, 1996;Katzenellenbogen et al, 1996). Biochemical and interactive cloning methods have led to isolation of 120 (Le Douarin et al, 1995), 125 (Onate et al, 1995), 140 (Cavailles et al, 1994(Cavailles et al, , 1995Halachmi et al, 1994), 160 (Halachmi et al, 1994;Cavailles et al, 1994), 168 (Chen and Evans, 1995) and 270 (Horlein et al, 1995) kDa proteins shown to associate with ligand-bound NHRs and function as positive (co-activators) or negative (corepressors) of nuclear receptor action by modulating interaction with the basal transcription complex. In addition, CBP (and related protein p300) has been described as a`co-integrator' of hormone receptor function through interaction with the nuclear receptor binding protein p160, TFIIB, and Jun/Fos (Kamei et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

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Characterization of Brx, a novel Dbl family member that modulates estrogen receptor action

et al. 1998

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Regulation of gene activation by the estrogen receptor (ER) is complex and involves co-regulatory proteins, oncoproteins (such as Fos and Jun), and phosphorylation signaling pathways. Here we report the cloning and initial characterization of a novel protein, Brx, that contains a region of identity to the oncogenic Rhoguanine nucleotide exchange (Rho-GEF) protein Lbc, and a unique region capable of binding to nuclear hormone receptors, including the ER. Western and immunohistochemistry studies showed Brx to be expressed in estrogen-responsive reproductive tissues, including breast ductal epithelium. Brx bound speci®cally to the ER via an interaction that required distinct regions of ER and Brx. Furthermore, overexpression of Brx in transfection experiments using an estrogenresponsive reporter revealed that Brx augmented gene activation by the ER in an element-speci®c and liganddependent manner. Moreover, activation of ER by Brx could be speci®cally inhibited by a dominant-negative mutant of Cdc42Hs, but not by dominant negative mutants of RhoA or Rac1. Taken together, these data suggest that Brx represents a novel modular protein that may integrate cytoplasmic signaling pathways involving Rho family GTPases and nuclear hormone receptors.

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Section: Identi®cation and Cloning Of Brx Cdnasupporting

confidence: 55%

Section: Brx Is Expressed In Reproductive and Immune Tissuessupporting

confidence: 55%

Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Characterization of Brx, a novel Dbl family member that modulates estrogen receptor action

et al. 1998

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“…Examples are RIP140 [31,32,33] and FKHR [34,35]. Recent evidence has demonstrated that the RFP/Mi-2β complex is associated with both gene repression [23] and expression [25] in a context-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Novel role of the RET finger protein in estrogen receptor-mediated transcription in MCF-7 cells

Townson

Kang

Lee

et al. 2006

Biochemical and Biophysical Research Communications

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The Scaffold attachment factor B1 (SAFB1) is an estrogen receptor (ESR1) repressor that has been proposed to inhibit breast tumorigenesis. To obtain insight into the functions of SAFB1 we utilized a yeast two-hybrid screen and identified the Ret finger protein (RFP) as interacting with the SAFB1 C-terminus. RFP is a member of the trimotif (TRIM) family of proteins, which we found widely expressed in a series of breast cancer cell lines. We confirmed the interaction between SAFB1 and RFP through in vitro (GST-pulldown) and in vivo (coimmunoprecipitations) assays. We hypothesized that SAFB1 functions as a scaffolding protein to recruit proteins such as RFP into proximity with ESR1. Consequently, we asked whether RFP would modulate ESR1 activity and we discovered that RFP was important for the ESR1-dependent expression of cyclin D1 (CCND1) and the progesterone receptor (PR) but not IRS1 or MYC. Although RFP did interact with ESR1 directly, it does coimmunoprecipitate with ESR1 demonstrating that RFP is found within the same protein complex. Chromatin immunoprecipitation assays (ChIP) located RFP to the TFF1 promoter, a known ESR1-regulated gene. Taken together, our study provides further evidence that coactivation and corepression are integrally linked processes and that RFP is a component of an ESR1 regulatory complex.

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Proteasome-mediated degradation of the vitamin D receptor (VDR) and a putative role for SUG1 interaction with the AF-2 domain of VDR

1998

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The AF-2 helix of nuclear receptors is essential for ligand-activated transcription, and it may function to couple the receptor to transcriptional coactivator proteins. This domain also contacts components of the proteasome machinery, suggesting that nuclear receptors may be targets for proteasome-mediated proteolysis. In the present study, we demonstrate that mSUG1 (P45), a component of the 26S proteasome, interacts in a 1,25-(OH)2D3-dependent manner with the AF-2 domain of the vitamin D receptor (VDR). Furthermore, treatment of ROS 17/2.8 osteosarcoma cells with the proteasome inhibitors MG132 or beta-lactone increased steady-state levels of the VDR protein. In the presence cycloheximide (10 microg/ml), the liganded VDR protein was degraded with a half-life of approximately 8 h, and this rate of degradation was completely blocked by 0.05 mM MG132. The role of SUG1 -VDR interaction in this process was investigated in transient expression studies. Overexpression of wild-type mSUG1 in ROS17/2.8 cells generated a novel proteolytic VDR fragment of approximately 50 kDa, and its production was blocked by proteasome inhibitors or by a nonhydrolyzable ATP analog. Parallel studies with SUG1 (K196H), a mutant that does not interact with the VDR, did not produce the 50 kDa VDR fragment. Functionally, expression of SUG1 in a VDR-responsive reporter gene assay resulted in a profound inhibition of 1,25-(OH)2D3-activated transcription, while expression of SUG1 (K196H) had no significant effect in this system. These data show that the AF-2 domain of VDR interacts with SUG1 in a 1,25-(OH)2D3-dependent fashion and that this interaction may target VDR to proteasome-mediated degradation as a means to downregulate the 1,25-(OH)2D3-activated transcriptional response.

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Nuclear factor RIP140 modulates transcriptional activation by the estrogen receptor.

Cited by 707 publications

References 65 publications

Characterization of Brx, a novel Dbl family member that modulates estrogen receptor action

Characterization of Brx, a novel Dbl family member that modulates estrogen receptor action

Novel role of the RET finger protein in estrogen receptor-mediated transcription in MCF-7 cells

Proteasome-mediated degradation of the vitamin D receptor (VDR) and a putative role for SUG1 interaction with the AF-2 domain of VDR

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