Billack Blase, Monteiro Alvaro N A
Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St John's University, Jamaica, NY 11439, USA.
Cancer Lett. 2005 Sep 8;227(1):1-7. doi: 10.1016/j.canlet.2004.11.006. Epub 2004 Dec 13.
Women carrying one mutated BRCA1 allele are at increased risk of developing breast and ovarian cancer but tumor initiation requires the loss of the wild-type allele indicating that it is a tumor suppressor gene. In the 10 years since the cloning of BRCA1, a function for the gene product in the DNA damage response has been established. However, identifying the exact biochemical activities of BRCA1 has been a more difficult task. Our current understanding suggests that the molecular functions mediated by the terminal ends of BRCA1, which include an E3 ubiquitin ligase activity at the N-terminus and a protein-protein interaction surface at the C-terminus, are critical to the function of this protein in the response to DNA damage.
携带一个突变型BRCA1等位基因的女性患乳腺癌和卵巢癌的风险增加，但肿瘤起始需要野生型等位基因的缺失，这表明它是一种肿瘤抑制基因。自BRCA1克隆以来的10年里，已经确定了该基因产物在DNA损伤反应中的功能。然而，确定BRCA1的确切生化活性一直是一项更艰巨的任务。我们目前的理解表明，由BRCA1末端介导的分子功能，包括N端的E3泛素连接酶活性和C端的蛋白质-蛋白质相互作用表面，对于该蛋白在DNA损伤反应中的功能至关重要。
