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BRCA1 tumor suppressor network: focusing on its tail

Germline mutations of the BRCA1 tumor suppressor gene are a major cause of familial breast and ovarian cancer. BRCA1 plays critical roles in the DNA damage response that regulates activities of multiple repair and checkpoint pathways for maintaining genome stability. The BRCT domains of BRCA1 consti...

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Detalles Bibliográficos
Autor principal: Wang, Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315748/
https://www.ncbi.nlm.nih.gov/pubmed/22369660
http://dx.doi.org/10.1186/2045-3701-2-6
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author Wang, Bin
author_facet Wang, Bin
author_sort Wang, Bin
collection PubMed
description Germline mutations of the BRCA1 tumor suppressor gene are a major cause of familial breast and ovarian cancer. BRCA1 plays critical roles in the DNA damage response that regulates activities of multiple repair and checkpoint pathways for maintaining genome stability. The BRCT domains of BRCA1 constitute a phospho-peptide binding domain recognizing a phospho-SPxF motif (S, serine; P, proline; × varies; F, phenylalanine). The BRCT domains are frequently targeted by clinically important mutations and most of these mutations disrupt the binding surface of the BRCT domains to phosphorylated peptides. The BRCT domain and its capability to bind phosphorylated protein is required for the tumor suppressor function of BRCA1. Through its BRCT phospho-binding ability BRCA1 forms at least three mutually exclusive complexes by binding to phosphorylated proteins Abraxas, Bach1 and CTIP. The A, B and C complexes, at lease partially undertake BRCA1's role in mechanisms of cell cycle checkpoint and DNA repair that maintain genome stability, thus may play important roles in BRCA1's tumor suppressor function.
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spelling pubmed-33157482012-03-31 BRCA1 tumor suppressor network: focusing on its tail Wang, Bin Cell Biosci Review Germline mutations of the BRCA1 tumor suppressor gene are a major cause of familial breast and ovarian cancer. BRCA1 plays critical roles in the DNA damage response that regulates activities of multiple repair and checkpoint pathways for maintaining genome stability. The BRCT domains of BRCA1 constitute a phospho-peptide binding domain recognizing a phospho-SPxF motif (S, serine; P, proline; × varies; F, phenylalanine). The BRCT domains are frequently targeted by clinically important mutations and most of these mutations disrupt the binding surface of the BRCT domains to phosphorylated peptides. The BRCT domain and its capability to bind phosphorylated protein is required for the tumor suppressor function of BRCA1. Through its BRCT phospho-binding ability BRCA1 forms at least three mutually exclusive complexes by binding to phosphorylated proteins Abraxas, Bach1 and CTIP. The A, B and C complexes, at lease partially undertake BRCA1's role in mechanisms of cell cycle checkpoint and DNA repair that maintain genome stability, thus may play important roles in BRCA1's tumor suppressor function. BioMed Central 2012-02-27 /pmc/articles/PMC3315748/ /pubmed/22369660 http://dx.doi.org/10.1186/2045-3701-2-6 Text en Copyright ©2012 Wang; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Wang, Bin
BRCA1 tumor suppressor network: focusing on its tail
title BRCA1 tumor suppressor network: focusing on its tail
title_full BRCA1 tumor suppressor network: focusing on its tail
title_fullStr BRCA1 tumor suppressor network: focusing on its tail
title_full_unstemmed BRCA1 tumor suppressor network: focusing on its tail
title_short BRCA1 tumor suppressor network: focusing on its tail
title_sort brca1 tumor suppressor network: focusing on its tail
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315748/
https://www.ncbi.nlm.nih.gov/pubmed/22369660
http://dx.doi.org/10.1186/2045-3701-2-6
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