Phosphorylation of ATR-interacting protein on Ser239 mediates an interaction with breast-ovarian cancer susceptibility 1 and checkpoint function.
Phosphorylation of ATR-interacting protein on Ser239 mediates an interaction with breast-ovarian cancer susceptibility 1 and checkpoint function.
复制标题
Ser239 上 ATR 相互作用蛋白的磷酸化介导与乳腺癌卵巢癌易感性 1 和检查点功能的相互作用。
DOI：
10.1158/0008-5472.can-07-0369
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发表时间：
2007
期刊：
影响因子：
11.2
通讯作者：
Halazonetis,ThanosD
中科院分区：
文献类型：
--
作者：
Venere,Monica;Snyder,Andrew;Zgheib,Omar;Halazonetis,ThanosD
The signaling of DNA damage and replication stress involves a multitude of proteins, including the kinases ataxia-telangiectasia mutated (ATM) and ATM and Rad3-related (ATR), and proteins with BRCA1 COOH-terminal (BRCT) domains. The BRCT domain–containing proteins facilitate the phosphorylation of ATM/ATR substrates and can be coimmunoprecipitated with ATM or ATR. However, their mode of interaction with the ATM/ATR kinases remains elusive. Here, we show that breast-ovarian cancer susceptibility 1 (BRCA1) interacts directly with ATR-interacting protein (ATRIP), an obligate partner of ATR. The interaction involves the BRCT domains of BRCA1 and Ser239of ATRIP, a residue that is phosphorylated in both irradiated and nonirradiated cells. Consistent with a role of BRCA1 in ATR signaling, substitution of Ser239of ATRIP with Ala leads to a G2-M checkpoint defect. We propose that a direct physical interaction between BRCA1 and ATRIP is required for the checkpoint function of ATR. [Cancer Res 2007;67(13):6100–5]
