Identification of DBC1 as a transcriptional repressor for BRCA1

被引：63

作者：

Hiraike, H. ^{[1
]}

Wada-Hiraike, O. ^{[1
]}

Nakagawa, S. ^{[1
]}

Koyama, S. ^{[1
]}

Miyamoto, Y. ^{[1
]}

Sone, K. ^{[1
]}

Tanikawa, M. ^{[1
]}

Tsuruga, T. ^{[1
]}

Nagasaka, K. ^{[1
]}

Matsumoto, Y. ^{[1
]}

Oda, K. ^{[1
]}

Shoji, K. ^{[1
]}

Fukuhara, H. ^{[2
]}

Saji, S. ^{[3
]}

Nakagawa, K. ^{[4
]}

Kato, S. ^{[5
,6
]}

Yano, T. ^{[1
]}

Taketani, Y. ^{[1
]}

机构：

[1] Univ Tokyo, Dept Obstet & Gynecol, Grad Sch Med, Bunkyo Ku, Tokyo 1138655, Japan

[2] Univ Tokyo, Dept Urol, Grad Sch Med, Bunkyo Ku, Tokyo 1138655, Japan

[3] Komagome Hosp, Tokyo Metropolitan Canc & Infect Dis Ctr, Bunkyo Ku, Tokyo 1138677, Japan

[4] Univ Tokyo, Dept Radiol, Grad Sch Med, Bunkyo Ku, Tokyo 1138655, Japan

[5] SORST, Japan Sci & Technol, Kawaguchi, Saitama 3320012, Japan

[6] Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130034, Japan

来源：

BRITISH JOURNAL OF CANCER | 2010年 / 102卷 / 06期

关键词：

DBC1; BRCA1; interaction; repression; POLYMERASE-II HOLOENZYME; DNA-DAMAGE; COMPLEX; SIRT1; ACTIVATION; REPAIR; EXPRESSION; APOPTOSIS; DOMAINS; PROTEIN;

D O I：

10.1038/sj.bjc.6605577

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BACKGROUND: DBC1/KIAA1967 (deleted in breast cancer 1) is a putative tumour-suppressor gene cloned from a heterozygously deleted region in breast cancer specimens. Caspase-dependent processing of DBC1 promotes apoptosis, and depletion of endogenous DBC1 negatively regulates p53-dependent apoptosis through its specific inhibition of SIRT1. Hereditary breast and ovarian cancer susceptibility gene product BRCA1, by binding to the promoter region of SIRT1, is a positive regulator of SIRT1 expression. METHODS: A physical interaction between DBC1 and BRCA1 was investigated both in vivo and in vitro. To determine the pathophysiological significance of DBC1, its role as a transcriptional factor was studied. RESULTS: We found a physical interaction between the amino terminus of DBC1 and the carboxyl terminus of BRCA1, also known as the BRCT domain. Endogenous DBC1 and BRCA1 form a complex in the nucleus of intact cells, which is exported to the cytoplasm during ultraviolet-induced apoptosis. We also showed that the expression of DBC1 represses the transcriptional activation function of BRCT by a transient expression assay. The expression of DBC1 also inhibits the transactivation of the SIRT1 promoter mediated by full-length BRCA1. CONCLUSION: These results revealed that DBC1 may modulate the cellular functions of BRCA1 and have important implications in the understanding of carcinogenesis in breast tissue. British Journal of Cancer (2010) 102, 1061-1067. doi:10.1038/sj.bjc.6605577 www.bjcancer.com Published online 16 February 2010 (C) 2010 Cancer Research UK

引用

页码：1061 / 1067

页数：7

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