In Vitro Enhanced Sensitivity to Cisplatin in D67Y BRCA1 RING Domain Protein

Breast Cancer: Basic and Clinical Research

Short Report

Adisorn Ratanaphan¹  Apichart Atipairin² 

[1] Laboratory of Pharmaceutical Biotechnology, Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai, Songkhla 90112, Thailand.;Laboratory of Pharmaceutical Biotechnology, Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai, Songkhla 90112, Thailand.;School of Pharmacy, Walailak University, Thasala, Nakhon Si Thammarat 80160, Thailand.;

关键词: BRCA1;    cisplatin;    ubiquitination;    cancer chemotherapy;   

DOI  :  10.4137/BCBCR.S8184

来源: Sage Journals

【 摘 要 】

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.

【 授权许可】

CC BY-NC   
© 2011 SAGE Publications.

【 图 表 】

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