Structural determinants of the BRCA1 : estrogen receptor interaction.

Abstract:

:Previously, we showed that the BRCA1 protein interacts directly and functionally with estrogen receptor-alpha (ER-alpha), resulting in the inhibition of estradiol (E2)-stimulated ER-alpha transcriptional activity. The interaction sites were mapped to the N-terminus of BRCA1 (within amino acids (aa) 1-302) and the ligand-binding domain/activation function-2 (LBD/AF-2) region (within aa 282-420) of ER-alpha. In this study, we have further characterized the structure/function relationship for the BRCA1 : ER-alpha interaction. We found that the N-terminal RING domain (aa 20-64) is not required for the BRCA1 : ER-alpha interaction. We identified two separate contact points for ER-alpha, one within aa 1-100 and the other within aa 100-200 of BRCA1; and we showed that each of these BRCA1 peptides interacts with BRCA1 in vitro and in vivo. By using different fragments of the BRCA1 N-terminus, we found that aa 67-100 and 101-133 are required for the interaction with ER-alpha, but that aa 1-67 and 134-302 are dispensible. Previously, we showed that BRCA1 aa 1-302 does not inhibit E2-stimulated ER-alpha transcriptional activity but does bind to ER-alpha and acts as a dominant negative inhibitor of the full-length BRCA1 protein. Somewhat surprisingly, we found that BRCA1 aa 1-100 and BRCA1 aa 101-200 (but not aa 201-300) each inhibited ER-alpha activity, although not as efficiently as full-length BRCA1. Mutations within an HIV Rev-like nuclear export signal that resembles a nuclear receptor corepressor motif (aa 86-95) impaired the ability of both truncated (aa 1-100) and full-length (aa 1-1863) BRCA1 proteins to interact with and/or repress ER-alpha activity. Based on these findings, a partial BRCA1 : ER-alpha three-dimensional structure is proposed. The implications of these findings for understanding the BRCA1 : ER-alpha interaction are discussed.

journal_name

Oncogene

journal_title

Oncogene

authors

Ma YX,Tomita Y,Fan S,Wu K,Tong Y,Zhao Z,Song LN,Goldberg ID,Rosen EM

doi

10.1038/sj.onc.1208190

subject

Has Abstract

pub_date

2005-03-10 00:00:00

pages

1831-46

issue

11

eissn

0950-9232

issn

1476-5594

pii

1208190

journal_volume

24

pub_type

杂志文章

相关文献

ONCOGENE文献大全
  • Elevated expression of the junB proto-oncogene is essential for v-fos induced transformation of Rat-1 cells.

    abstract::We previously described the isolation of non-tumorigenic revertants from mutagenized populations of v-fos-transformed Rat-1 cells (Zarbl et al., 1987). In the present study we examined the possibility that the revertant phenotype resulted from mutations that altered the expression or activities of the c-jun or junB pr...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Van Amsterdam JR,Wang Y,Sullivan RC,Zarbl H

    更新日期:1994-10-01 00:00:00

  • Surfactant protein D inhibits activation of non-small cell lung cancer-associated mutant EGFR and affects clinical outcomes of patients.

    abstract::Tyrosine kinase inhibitor (TKI)-sensitive and TKI-resistant mutations of epidermal growth factor receptor (EGFR) are associated with lung adenocarcinoma. EGFR mutants were previously shown to exhibit ligand-independent activation. We have previously demonstrated that pulmonary surfactant protein D (SP-D, SFTPD) suppre...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2017.253

    authors: Umeda Y,Hasegawa Y,Otsuka M,Ariki S,Takamiya R,Saito A,Uehara Y,Saijo H,Kuronuma K,Chiba H,Ohnishi H,Sakuma Y,Takahashi H,Kuroki Y,Takahashi M

    更新日期:2017-11-16 00:00:00

  • Frequent hypermethylation of MLH1 promoter in normal endometrium of patients with endometrial cancers.

    abstract::Silencing of the MLH1 gene by promoter hypermethylation is the mechanism underlying the microsatellite instability (MSI) phenotype in endometrial cancers. However, the profile of CpG methylation in a wide range of MLH1 promoters in endometrial cancers and in the normal endometrium is largely unknown. The present study...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206365

    authors: Kanaya T,Kyo S,Maida Y,Yatabe N,Tanaka M,Nakamura M,Inoue M

    更新日期:2003-04-17 00:00:00

  • pRb and Cdk regulation by N-(4-hydroxyphenyl)retinamide.

    abstract::The cancer chemopreventive synthetic retinoid N-(4-hydroxyphenyl)retinamide (HPR) can inhibit the growth and induce apoptosis of tumor cells. In this study we analysed the growth suppressive effect of HPR on human breast cancer cell lines in vitro and the role of the retinoblastoma protein (pRb) in this response. Trea...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1203743

    authors: Panigone S,Debernardi S,Taya Y,Fontanella E,Airoldi R,Delia D

    更新日期:2000-08-17 00:00:00

  • Oncogenic Ras-induced secretion of a novel inhibitor of skeletal myoblast differentiation.

    abstract::Expression of oncogenic H-Ras in 23A2 myoblasts (A2:H-Ras cells) is sufficient to induce both a transformed phenotype and a differentiation-defective phenotype. Because oncogenic Ras is known to induce the secretion of several different growth factors involved in maintaining the transformed phenotype of both fibroblas...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1201423

    authors: Weyman CM,Wolfman A

    更新日期:1997-11-20 00:00:00

  • The protein-tyrosine phosphatase DEP-1 modulates growth factor-stimulated cell migration and cell-matrix adhesion.

    abstract::Density-enhanced protein-tyrosine phosphatase-1 (DEP-1 also CD148) is a transmembrane molecule with a single intracellular PTP domain. It has recently been proposed to function as a tumor suppressor. We have previously shown that DEP-1 dephosphorylates the activated platelet-derived growth factor (PDGF) beta-receptor ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206652

    authors: Jandt E,Denner K,Kovalenko M,Ostman A,Böhmer FD

    更新日期:2003-07-03 00:00:00

  • Evidence for GEAPS, novel Glial E2F1-Associated Proteins in hamster glioma cells induced by the human neurotropic polyomavirus, JCV.

    abstract::Injection of the human neurotropic polyomavirus, JCV, into neonatal hamsters causes tumors of glial origin. Previously, a rapidly proliferating cell line, HJC-15, which expresses high levels of the viral T-antigen, had been established from JCV-induced hamster glial tumors. In our analyses of the mechanisms involved i...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Raj GV,Ansari SA,Khalili K

    更新日期:1996-03-21 00:00:00

  • A novel p53 mutational hotspot in skin tumors from UV-irradiated Xpc mutant mice alters transactivation functions.

    abstract::A mutation in codon 122 of the mouse p53 gene resulting in a T to L amino acid substitution (T122-->L) is frequently associated with skin cancer in UV-irradiated mice that are both homozygous mutant for the nucleotide excision repair (NER) gene Xpc (Xpc(-/-)) and hemizygous mutant for the p53 gene. We investigated the...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1205779

    authors: Inga A,Nahari D,Velasco-Miguel S,Friedberg EC,Resnick MA

    更新日期:2002-08-22 00:00:00

  • Midkine (MDK) growth factor: a key player in cancer progression and a promising therapeutic target.

    abstract::Midkine is a heparin-binding growth factor, originally reported as the product of a retinoic acid-responsive gene during embryogenesis, but currently viewed as a multifaceted factor contributing to both normal tissue homeostasis and disease development. Midkine is abnormally expressed at high levels in various human m...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/s41388-019-1124-8

    authors: Filippou PS,Karagiannis GS,Constantinidou A

    更新日期:2020-03-01 00:00:00

  • Delayed cyclin B1 expression during the G2 arrest following DNA damage.

    abstract::Exposure of cells to DNA damaging agents results in a G2 arrest. Exposure of HeLa cells to camptothecin, etoposide or nitrogen mustard for 1 h in S phase resulted in delayed expression of cyclin B1 mRNA during the G2 arrest. Initially the levels of cyclin B1 protein were low as well; however, with extended time the ce...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Maity A,Hwang A,Janss A,Phillips P,McKenna WG,Muschel RJ

    更新日期:1996-10-17 00:00:00

  • Low expression of pro-apoptotic Bcl-2 family proteins sets the apoptotic threshold in Waldenström macroglobulinemia.

    abstract::Waldenström macroglobulinemia (WM) is a proliferative disorder of IgM-secreting, lymphoplasmacytoid cells that inhabit the lymph nodes and bone marrow. The disease carries a high prevalence of activating mutations in MyD88 (91%) and CXCR4 (28%). Because signaling through these pathways leads to Bcl-xL induction, we ex...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2015.103

    authors: Gaudette BT,Dwivedi B,Chitta KS,Poulain S,Powell D,Vertino P,Leleu X,Lonial S,Chanan-Khan AA,Kowalski J,Boise LH

    更新日期:2016-01-28 00:00:00

  • A 5'-CG-3'-rich region in the promoter of the transcriptionally frequently silenced RET protooncogene lacks methylated cytidine residues.

    abstract::In a large proportion of familial and sporadic cases of Hirschsprung disease (HSCR) mutations in the RET (rearranged during transfection) protooncogene have been described. We have investigated the structure of the RET gene promoter and have analysed a region of approximately 1000 nucleotides in its promoter and 5'-up...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202165

    authors: Munnes M,Patrone G,Schmitz B,Romeo G,Doerfler W

    更新日期:1998-11-19 00:00:00

  • Distinct changes in gene expression induced by A-Myb, B-Myb and c-Myb proteins.

    abstract::The c-Myb, A-Myb and B-Myb transcription factors have nearly identical DNA-binding domains, activate the same reporter gene constructs in animal cells, but have different biological roles. The Myb proteins are often coexpressed in the same cells, raising questions about whether they activate similar or distinct gene e...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206131

    authors: Rushton JJ,Davis LM,Lei W,Mo X,Leutz A,Ness SA

    更新日期:2003-01-16 00:00:00

  • Repression of cancer cell senescence by PKCι.

    abstract::Senescence is an irreversible growth arrest phenotype adopted by cells that has a key role in protecting organisms from cancer. There is now considerable interest in therapeutic strategies that reactivate this process to control the growth of cancer cells. Protein kinase-Cι (PKCι) is a member of the atypical PKC famil...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.524

    authors: Paget JA,Restall IJ,Daneshmand M,Mersereau JA,Simard MA,Parolin DA,Lavictoire SJ,Amin MS,Islam S,Lorimer IA

    更新日期:2012-08-02 00:00:00

  • Adrenomedullin antagonist suppresses in vivo growth of human pancreatic cancer cells in SCID mice by suppressing angiogenesis.

    abstract::Since it is reported that adrenomedullin (AM) upregulated by hypoxia inhibits hypoxic cell death, we examined the effects of AM antagonist (AM C-terminal fragment; AM(22-52)) on the growth of pancreatic cancer cells. We, for the first time, demonstrated that AM antagonist significantly reduced the in vivo growth of th...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206207

    authors: Ishikawa T,Chen J,Wang J,Okada F,Sugiyama T,Kobayashi T,Shindo M,Higashino F,Katoh H,Asaka M,Kondo T,Hosokawa M,Kobayashi M

    更新日期:2003-02-27 00:00:00

  • Sustained TGF beta exposure suppresses Smad and non-Smad signalling in mammary epithelial cells, leading to EMT and inhibition of growth arrest and apoptosis.

    abstract::To better understand the dual, tumour-suppressive and tumour-promoting function of transforming growth factor-beta (TGFbeta), we analysed mammary epithelial NMuMG cells in response to short and long-term TGFbeta exposure. NMuMG cells became proliferation-arrested and apoptotic after exposure to TGFbeta for 2-5 days, w...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210741

    authors: Gal A,Sjöblom T,Fedorova L,Imreh S,Beug H,Moustakas A

    更新日期:2008-02-21 00:00:00

  • NFATc2 is an intrinsic regulator of melanoma dedifferentiation.

    abstract::Melanoma dedifferentiation, characterized by the loss of MITF and MITF regulated genes and by upregulation of stemness markers as CD271, is implicated in resistance to chemotherapy, target therapy and immunotherapy. The identification of intrinsic mechanisms fostering melanoma dedifferentiation may provide actionable ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2015.355

    authors: Perotti V,Baldassari P,Molla A,Vegetti C,Bersani I,Maurichi A,Santinami M,Anichini A,Mortarini R

    更新日期:2016-06-02 00:00:00

  • RET(MEN 2B) is active in the endoplasmic reticulum before reaching the cell surface.

    abstract::MEN 2B (multiple endocrine neoplasia type 2B) is an autosomal dominant cancer syndrome caused by an oncogenic form of the receptor tyrosine kinase REarranged during transfection (RET). The MEN 2B syndrome is associated with an abnormal autophosphorylation of the mutated receptor even without ligand-stimulation. Here, ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210591

    authors: Runeberg-Roos P,Virtanen H,Saarma M

    更新日期:2007-12-13 00:00:00

  • TRAIL is a key target in S-phase slowing-dependent apoptosis induced by interferon-beta in cervical carcinoma cells.

    abstract::Interferon (IFN)-beta induces S-phase slowing and apoptosis in human papilloma virus (HPV)-positive cervical carcinoma cell line ME-180. Here, we show that apoptosis is a consequence of the S-phase lengthening imposed by IFN-beta, demonstrating the functional correlation between S-phase alteration and apoptosis induct...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208403

    authors: Vannucchi S,Chiantore MV,Fiorucci G,Percario ZA,Leone S,Affabris E,Romeo G

    更新日期:2005-04-07 00:00:00

  • Correction: FGFR1-ERK1/2-SOX2 axis promotes cell proliferation, epithelial-mesenchymal transition, and metastasis in FGFR1-amplified lung cancer.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Oncogene

    pub_type: 已发布勘误

    doi:10.1038/s41388-020-01441-6

    authors: Wang K,Ji W,Yu Y,Li Z,Niu X,Xia W,Lu S

    更新日期:2020-10-01 00:00:00

  • Apc and p53 interaction in DNA damage and genomic instability in hepatocytes.

    abstract::Disruption of Apc (adenomatous polyposis coli) within hepatocytes activates Wnt signalling, perturbs differentiation and ultimately leads to neoplasia. Apc negatively regulates Wnt signalling but is also involved in organizing the cytoskeleton and may have a role in chromosome segregation. In vitro studies have implic...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2014.342

    authors: Méniel V,Megges M,Young MA,Cole A,Sansom OJ,Clarke AR

    更新日期:2015-07-30 00:00:00

  • Rho GTPases: Anti- or pro-neoplastic targets?

    abstract::Rho GTPases are critical signal transducers of multiple pathways. They have been proposed to be useful anti-neoplastic targets for over two decades, especially in Ras-driven cancers. Until recently, however, few in vivo studies had been carried out to test this premise. Several recent mouse model studies have verified...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/onc.2016.473

    authors: Zandvakili I,Lin Y,Morris JC,Zheng Y

    更新日期:2017-06-08 00:00:00

  • Deacetylase recruitment by the C/H3 domain of the acetyltransferase p300.

    abstract::The balance between acetylation and deacetylation of histone and nonhistone proteins controls gene expression in a variety of cellular processes, with transcription being activated by acetyltransferases and silenced by deacetylases. We report here the formation and enzymatic characterization of a complex between the a...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1207327

    authors: Simone C,Stiegler P,Forcales SV,Bagella L,De Luca A,Sartorelli V,Giordano A,Puri PL

    更新日期:2004-03-18 00:00:00

  • Merlin regulates transmembrane receptor accumulation and signaling at the plasma membrane in primary mouse Schwann cells and in human schwannomas.

    abstract::The NF2 gene product, merlin/schwannomin, is a cytoskeleton organizer with unique growth-inhibiting activity in specific cell types. A narrow spectrum of tumors is associated with NF2 deficiency, mainly schwannomas and meningiomas, suggesting cell-specific mechanisms of growth control. We have investigated merlin func...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2008.427

    authors: Lallemand D,Manent J,Couvelard A,Watilliaux A,Siena M,Chareyre F,Lampin A,Niwa-Kawakita M,Kalamarides M,Giovannini M

    更新日期:2009-02-12 00:00:00

  • A model for GFR alpha 4 function and a potential modifying role in multiple endocrine neoplasia 2.

    abstract::Mutations of the RET proto-oncogene are found in the majority of patients with the inherited cancer syndrome multiple endocrine neoplasia type 2 (MEN 2). A minority of cases, however, have no detectable RET mutation and there is considerable phenotypic variation within and among MEN 2 families with the same RET mutati...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1207826

    authors: Vanhorne JB,Andrew SD,Harrison KJ,Taylor SA,Thomas B,McDonald TJ,Ainsworth PJ,Mulligan LM

    更新日期:2005-02-03 00:00:00

  • Control of MAPK signalling: from complexity to what really matters.

    abstract::Oncogenesis results from changes in kinetics or in abundance of proteins in signal transduction networks. Recently, it was shown that control of signalling cannot reside in a single gene product, and might well be dispersed over many components. Which of the reactions in these complex networks are most important, and ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208817

    authors: Hornberg JJ,Binder B,Bruggeman FJ,Schoeberl B,Heinrich R,Westerhoff HV

    更新日期:2005-08-25 00:00:00

  • Predominant requirement of Bax for apoptosis in HCT116 cells is determined by Mcl-1's inhibitory effect on Bak.

    abstract::The intrinsic mitochondrial apoptotic pathway acts through two core pro-apoptotic proteins Bax (Bcl2-associated X protein) and Bak (Bcl2-antagonist/killer 1). Although Bax and Bak seem to have redundant roles in apoptosis, accumulating evidence also suggests that they might not be interchangeable under certain conditi...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.497

    authors: Wang C,Youle RJ

    更新日期:2012-06-28 00:00:00

  • Snail silencing effectively suppresses tumour growth and invasiveness.

    abstract::The transcription factor Snail has been recently proposed as an important mediator of tumour invasion because of its role in downregulation of E-cadherin and induction of epithelial-mesenchymal transitions (EMT). This behaviour has led to the consideration of Snail as a potential therapeutic target to block tumour pro...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209997

    authors: Olmeda D,Jordá M,Peinado H,Fabra A,Cano A

    更新日期:2007-03-22 00:00:00

  • The RON receptor tyrosine kinase promotes MSP-independent cell spreading and survival in breast epithelial cells.

    abstract::The recepteur d'origine nantais (RON) is a receptor tyrosine kinase (RTK) in the scatter factor family, which includes the c-Met receptor. RON exhibits increased expression in a significant number of human breast cancer tissues as well as in many established breast cancer cell lines. Recent studies have indicated that...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2008.383

    authors: Feres KJ,Ischenko I,Hayman MJ

    更新日期:2009-01-15 00:00:00

  • The human F box protein beta-Trcp associates with the Cul1/Skp1 complex and regulates the stability of beta-catenin.

    abstract::Ubiquitin-conjugation targets numerous cellular regulators for proteasome-mediated degradation. Thus, the identification of ubiquitin ligases and their physiological substrates is crucially important, especially for those cases in which aberrant levels of regulatory proteins (e.g., beta-catenin, p27) result from a der...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202653

    authors: Latres E,Chiaur DS,Pagano M

    更新日期:1999-01-28 00:00:00