BRCA1 ubiquitinates its phosphorylation-dependent binding partner CtIP (Genes & Develop, 2006, 20:1721-1726)

報告日期: 2007/11/13
報告時間: 16:10/17:00
報告學生: 林麗芳
講評老師: 黃溫雅
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BRCA1 ubiquitinates its phosphorylation-dependent binding partner CtIP

 

Xiaochun Yu, Shuang Fu, Maoyi Lai, Richard Baer and Junjie Chen

Genes & Dev. 2006 20: 1721-1726

 

Speaker: 林麗芳

Commentator: 黃溫雅 老師

Date: 2007/11/13 () 16:10~17:00

Place: Room 602

 

Abstract :

The BRCA1 gene (Breast Cancer Susceptibility Gene 1) contains an N-terminal Ring domain and tandem C-terminal BRCT domains. The Ring domain of BRCA1 has E3 ubiquitin ligase activity, while the BRCT domain has recently been demonstrated to be a phospho-protein interaction domain. Breast cancer-associated mutations have been found in both the Ring and BRCT domains of BRCA1, suggesting that these two regions are critical for BRCA1 tumor suppression. In this paper, the authors wanted to explore whether these domains may function together in a coordinated fashion. Previous studies have been demonstrated that CtIP (CtBP-interacting protein) is a phosphorylation-dependent binding partner of the BRCA1 BRCT domain. It transiently interacts with BRCA1 in G2 phase, and participates in BRCA1-dependent G2/M checkpoint control. Therefore, they wanted to investigate whether a BRCA1 Ring domain catalyzes CtIP ubiquitination in a manner that depends on a phosphorylation-mediated interaction between CtIP and BRCA1 BRCT domains. The results show that the ubiquitination of CtIP is specifically dependent on the E3 ligase activity of BRCA1. However, BRCA1-dependent ubiquitination of CtIP does not target CtIP for degradation. Moreover, ubiquitinated CtIP associates with chromatin and may play a pivotal role in BRCA1-dependent G2/M checkpoint control following DNA damage. Above all, BRCA1 Ring domain and BRCT domains act together and regulate various BRCA1-dependent functions through protein ubiquitination.

 

References:

1. Lorick, K.L., Jensen, J.P., Fang, S., Ong, A.M., Hatakeyama, S., and Weissman, A.M. 1999. RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination. Proc. Natl. Acad. Sci. 96:11364–11369.

2. Yu, X. and Chen, J. 2004. DNA damage-induced cell cycle checkpoint control requires CtIP, a phosphorylation-dependent binding partner of BRCA1 C-terminal domains. Mol. Cell. Biol. 24: 9478–9486.