期刊
SCIENCE
卷 334, 期 6055, 页码 525-528出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1209909
关键词
-
资金
- NIH [R01-CA137023, P01-CA97403, R01-HD40916]
- Susan G. Komen Breast Cancer fellowship
- Kirschstein National Research Service [F31-CA132626, F32-HD51392]
- National Cancer Institute [T32-CA09503]
- U.S. Department of Defense (DOD) [BC083089]
- DOD [W81XWH04-1-0477]
- Breast Cancer Research Foundation
Germline mutations of the breast cancer 1 (BRCA1) gene are a major cause of familial breast and ovarian cancer. The BRCA1 protein displays E3 ubiquitin ligase activity, and this enzymatic function is thought to be required for tumor suppression. To test this hypothesis, we generated mice that express an enzymatically defective Brca1. We found that this mutant Brca1 prevents tumor formation to the same degree as does wild-type Brca1 in three different genetically engineered mouse (GEM) models of cancer. In contrast, a mutation that ablates phosphoprotein recognition by the BRCA C terminus (BRCT) domains of BRCA1 elicits tumors in each of the three GEM models. Thus, BRCT phosphoprotein recognition, but not the E3 ligase activity, is required for BRCA1 tumor suppression.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据