BRCA1: a scaffold for p53 response?

Peter Hohenstein, Rachel H Giles

Research output: Contribution to journalArticlepeer-review

Abstract

The tumor suppressor gene p53, mutated in ≈50% of all human cancers, encodes a sequence-specific DNA-binding transcription factor. Target genes can be roughly categorized into two groups: genes that temporarily halt cell-cycle progression and genes that promote apoptosis. However, the molecular mechanism by which p53 senses whether to initiate cell-cycle arrest or apoptosis following cellular stress remains unknown. Here, we argue that the breast cancer tumor suppressor gene product BRCA1 might function as a molecular scaffold, assembling proteins involved in the fine-tuning of the p53 response.

Since the identification of BRCA1 mutations in familial breast and ovarian tumors, many functional studies have implicated BRCA1 in a surprisingly diverse array of biological processes [1]. Most studies have been aimed at the interaction of BRCA1 with DNA repair proteins such as RAD51, but convincing data supporting a role in transcriptional regulation, ubiquitination and chromosome remodeling are available. At present, over 30 proteins associated with BRCA1 have been identified, binding directly, indirectly or as part of larger multiprotein complexes. Many, if not all, of these proteins are involved in one or more of the processes mentioned above, suggesting a scaffold-like function for BRCA1, coordinating essential components in a spatial and temporal manner. The BASC complex (BRCA1-associated genome surveillance complex), in which BRCA1 binds many different proteins capable of both recognition and repair of damaged DNA, might illustrate this principle [2].
Original languageEnglish
Pages (from-to)489-94
Number of pages6
JournalTrends in Genetics
Volume19
Issue number9
DOIs
Publication statusPublished - 2003

Keywords

  • BRCA1 Protein/genetics
  • BRCA1 Protein/physiology
  • Breast Neoplasms/genetics
  • Humans
  • Tumor Suppressor Protein p53/genetics
  • Tumor Suppressor Protein p53/physiology

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