Liu, W and Zong, W and Wu, G and Fujita, T and Li, W and Wu, J and Wan, Y
(2010)
Turnover of BRCA1 involves in radiation-induced apoptosis.
PLoS ONE, 5 (12).
Abstract
Background: Germ-line mutations of the breast cancer susceptibility gene-1 (BRCA1) increase the susceptibility to tumorigenesis. The function of BRCA1 is to regulate critical cellular processes, including cell cycle progression, genomic integrity, and apoptosis. Studies on the regulation of BRCA1 have focused intensely on transcription and phosphorylation mechanisms. Proteolytic regulation of BRCA1 in response to stress signaling remains largely unknown. The manuscript identified a novel mechanism by which BRCA1 is regulated by the ubiquitin-dependent degradation in response to ionization. Methodology/Principal Findings: Here, we report that severe ionization triggers rapid degradation of BRCA1, which in turn results in the activation of apoptosis. Ionization-induced BRCA1 turnover is mediated via an ubiquitin-proteasomal pathway. The stabilization of BRCA1 significantly delays the onset of ionization-induced apoptosis. We have mapped the essential region on BRCA1, which mediates its proteolysis in response to ionization. Moreover, we have demonstrated that BRCA1 protein is most sensitive to degradation when ionization occurs during G2/M and S phase. Conclusions/Significance: Our results suggest that ubiquitin-proteasome plays an important role in regulating BRCA1 during genotoxic stress. Proteolytic regulation of BRCA1 involves in ionization-induced apoptosis. © 2010 Liu et al.
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Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
Creators | Email | Pitt Username | ORCID  |
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Liu, W | | | | Zong, W | | | | Wu, G | | | | Fujita, T | | | | Li, W | | | | Wu, J | | | | Wan, Y | yow4@pitt.edu | YOW4 | |
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Contributors: |
Contribution | Contributors Name | Email | Pitt Username | ORCID  |
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Editor | Wu, Gen Sheng | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
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Date: |
1 December 2010 |
Date Type: |
Publication |
Journal or Publication Title: |
PLoS ONE |
Volume: |
5 |
Number: |
12 |
DOI or Unique Handle: |
10.1371/journal.pone.0014484 |
Schools and Programs: |
School of Medicine > Cell Biology and Molecular Physiology |
Refereed: |
Yes |
MeSH Headings: |
Animals; Apoptosis; BRCA1 Protein--biosynthesis; Cell Cycle; Fibroblasts--metabolism; Gamma Rays; Gene Expression Regulation, Neoplastic--radiation effects; Genes, BRCA1; Genome--radiation effects; HeLa Cells; Humans; Ions; Mice; Phosphorylation; Proteasome Endopeptidase Complex--metabolism; Ubiquitin--metabolism |
Other ID: |
NLM PMC3013096 |
PubMed Central ID: |
PMC3013096 |
PubMed ID: |
21217819 |
Date Deposited: |
25 Aug 2012 16:39 |
Last Modified: |
02 Feb 2019 16:58 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/13671 |
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