Home LiteratureArticle Details
PMID: 9482880 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

BRCA1 regulates p53-dependent gene expression.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 95 ·No. 5 ·1998-03-03 ·Pages 2302-6

Ouchi T, Monteiro AN, August A, Aaronson SA, Hanafusa H

Abstract

Mutations in BRCA1 are present in 45% of families that segregate with susceptibility for breast cancer and in 80-90% of families with both breast and ovarian cancer. Here we report that BRCA1 stimulates artificial and genomic promoter constructs containing p53-responsive elements. This activity of BRCA1 depends on the presence of wild-type p53, which was shown by using mouse fibroblasts expressing temperature-sensitive forms of p53, or p53(+/+) and p53(-/-) fibroblasts obtained from p53 knockout mice. Furthermore, mutant forms of BRCA1 lacking the C-terminal second BRCA1 C-terminal (BRCT) domain showed reduced p53-mediated transcriptional activation. Finally, we found that BRCA1 coimmunoprecipitates with p53, in vitro and in vivo. These findings suggest a function of BRCA1 as a p53 coactivator.

MeSH Terms
Animals BRCA1 Protein/genetics,metabolism Breast Cell Line Epithelial Cells Female Gene Expression Regulation Genes, BRCA1 Genes, Reporter Glutathione Transferase/biosynthesis Humans Kidney Neoplasms Luciferases/biosynthesis Mice Polymerase Chain Reaction Promoter Regions, Genetic Recombinant Fusion Proteins/biosynthesis Transfection Tumor Cells, Cultured Tumor Suppressor Protein p53/metabolism
Chemicals
BRCA1 Protein Recombinant Fusion Proteins Tumor Suppressor Protein p53 Luciferases Glutathione Transferase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Ouchi T
Laboratory of Molecular Oncology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Monteiro A N
August A
Aaronson S A
Hanafusa H
References (35)
35 references, click to expand
  1. Allosteric activation of latent p53 tetramers.
    Curr Biol. 1994 Oct 1;4(10):865-75 PMID: 7850419
  2. Post-translational modification of p53.
    Semin Cancer Biol. 1994 Jun;5(3):203-10 PMID: 7948948
  3. Activation of p53 sequence-specific DNA binding by short single strands of DNA requires the p53 C-terminus.
    Cell. 1995 Jun 30;81(7):1021-9 PMID: 7600571
  4. Small peptides activate the latent sequence-specific DNA binding function of p53.
    Cell. 1995 Oct 20;83(2):237-45 PMID: 7585941
  5. Aberrant subcellular localization of BRCA1 in breast cancer.
    Science. 1995 Nov 3;270(5237):789-91 PMID: 7481765
  6. Germline mutations of the BRCA1 gene in breast and ovarian cancer families provide evidence for a genotype-phenotype correlation.
    Nat Genet. 1995 Dec;11(4):428-33 PMID: 7493024
  7. Growth retardation and tumour inhibition by BRCA1.
    Nat Genet. 1996 Mar;12(3):298-302 PMID: 8589721
  8. Location of BRCA1 in human breast and ovarian cancer cells.
    Science. 1996 Apr 5;272(5258):123-6 PMID: 8600523
  9. p53 is linked directly to homologous recombination processes via RAD51/RecA protein interaction.
    EMBO J. 1996 Apr 15;15(8):1992-2002 PMID: 8617246
  10. p53: puzzle and paradigm.
    Genes Dev. 1996 May 1;10(9):1054-72 PMID: 8654922
  11. BRCA1 is a 220-kDa nuclear phosphoprotein that is expressed and phosphorylated in a cell cycle-dependent manner.
    Cancer Res. 1996 Jul 15;56(14):3168-72 PMID: 8764100
  12. Transcriptional activation by BRCA1.
    Nature. 1996 Aug 22;382(6593):678-9 PMID: 8751436
  13. Association of BRCA1 with Rad51 in mitotic and meiotic cells.
    Cell. 1997 Jan 24;88(2):265-75 PMID: 9008167
  14. A superfamily of conserved domains in DNA damage-responsive cell cycle checkpoint proteins.
    FASEB J. 1997 Jan;11(1):68-76 PMID: 9034168
  15. BRCA1 is a component of the RNA polymerase II holoenzyme.
    Proc Natl Acad Sci U S A. 1997 May 27;94(11):5605-10 PMID: 9159119
  16. Synergistic activation of transcription by CBP and p53.
    Nature. 1997 Jun 19;387(6635):819-23 PMID: 9194564
  17. Binding and modulation of p53 by p300/CBP coactivators.
    Nature. 1997 Jun 19;387(6635):823-7 PMID: 9194565
  18. BRCA1 is a cell cycle-regulated nuclear phosphoprotein.
    Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7138-43 PMID: 9207057
  19. Repression of p53-mediated transcription by MDM2: a dual mechanism.
    Genes Dev. 1997 Aug 1;11(15):1974-86 PMID: 9271120
  20. Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain.
    Cell. 1997 Aug 22;90(4):595-606 PMID: 9288740
  21. Arrest of the cell cycle by the tumour-suppressor BRCA1 requires the CDK-inhibitor p21WAF1/CiP1.
    Nature. 1997 Sep 11;389(6647):187-90 PMID: 9296497
  22. Common BRCA1 variants and transcriptional activation.
    Am J Hum Genet. 1997 Sep;61(3):761-2 PMID: 9326340
  23. Evidence for a transcriptional activation function of BRCA1 C-terminal region.
    Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13595-9 PMID: 8942979
  24. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms.
    Science. 1990 Nov 30;250(4985):1233-8 PMID: 1978757
  25. Cellular localization and cell cycle regulation by a temperature-sensitive p53 protein.
    Genes Dev. 1991 Feb;5(2):151-9 PMID: 1995413
  26. p53 mutations in human cancers.
    Science. 1991 Jul 5;253(5015):49-53 PMID: 1905840
  27. The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation.
    Cell. 1992 Jun 26;69(7):1237-45 PMID: 1535557
  28. Wild-type p53 mediates positive regulation of gene expression through a specific DNA sequence element.
    Genes Dev. 1992 Jul;6(7):1143-52 PMID: 1628822
  29. The p53-mdm-2 autoregulatory feedback loop.
    Genes Dev. 1993 Jul;7(7A):1126-32 PMID: 8319905
  30. Heterodimerization of the transcription factors E2F-1 and DP-1 leads to cooperative trans-activation.
    Genes Dev. 1993 Oct;7(10):1850-61 PMID: 8405995
  31. WAF1, a potential mediator of p53 tumor suppression.
    Cell. 1993 Nov 19;75(4):817-25 PMID: 8242752
  32. Tumor spectrum analysis in p53-mutant mice.
    Curr Biol. 1994 Jan 1;4(1):1-7 PMID: 7922305
  33. BRCA1 mutations in primary breast and ovarian carcinomas.
    Science. 1994 Oct 7;266(5182):120-2 PMID: 7939630
  34. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1.
    Science. 1994 Oct 7;266(5182):66-71 PMID: 7545954
  35. p53 and its 14 kDa C-terminal domain recognize primary DNA damage in the form of insertion/deletion mismatches.
    Cell. 1995 Jun 30;81(7):1013-20 PMID: 7600570
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.95.5.2302
Published
1998-03-03
Pages
2302-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC19327
Subset
IM
Grants
NCI NIH HHS · 1P50CA68425 · United States
NCI NIH HHS · CA44356 · United States
External Links
PubMed source DOI: 10.1073/pnas.95.5.2302 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2