In Vitro Enhanced Sensitivity to Cisplatin in D67Y BRCA1 RING Domain Protein.
In Vitro Enhanced Sensitivity to Cisplatin in D67Y BRCA1 RING Domain Protein.
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DOI：
10.4137/bcbcr.s8184
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发表时间：
2011
期刊：
影响因子：
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通讯作者：
Ratanaphan A
中科院分区：
文献类型：
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作者：
Atipairin A;Ratanaphan A
BRCA 1是一种肿瘤抑制蛋白，通过DNA损伤修复、转录调控、细胞周期检查点和蛋白质泛素化等多种功能参与维持基因组完整性。BRCA 1-BARD 1 RING复合物具有E3泛素连接酶功能，在响应DNA损伤修复中发挥重要作用。BRCA 1相关的癌症已显示出对化疗药物的超敏反应。在这里，我们研究了体外E3泛素连接酶活性和顺铂敏感性的错义突变D 67 Y BRCA 1环域的功能后果。D 67 Y BRCA 1 RING结构域蛋白表现出降低的泛素化功能，并且比D 67 E或野生型BRCA 1 RING结构域蛋白对药物更敏感。这一证据强调了使用BRCA 1功能障碍作为乳腺癌化疗反应的重要决定因素的潜力。
BRCA1 is a tumor suppressor protein involved in maintaining genomic integrity through multiple functions in DNA damage repair, transcriptional regulation, cell cycle checkpoint, and protein ubiquitination. The BRCA1-BARD1 RING complex has an E3 ubiquitin ligase function that plays essential roles in response to DNA damage repair. BRCA1-associated cancers have been shown to confer a hypersensitivity to chemotherapeutic agents. Here, we have studied the functional consequence of the in vitro E3 ubiquitin ligase activity and cisplatin sensitivity of the missense mutation D67Y BRCA1 RING domain. The D67Y BRCA1 RING domain protein exhibited the reduced ubiquitination function, and was more susceptible to the drug than the D67E or wild-type BRCA1 RING domain protein. This evidence emphasized the potential of using the BRCA1 dysfunction as an important determinant of chemotherapy responses in breast cancer.