BRCA1 Function

描述：(申请人提供)乳腺癌与损失有关 肿瘤抑制蛋白的功能及其激活 致癌基因。在所有乳腺癌病例中，约4%与 BRCA1基因突变的遗传。BRCA1基因携带突变 在乳房发病率增加的家庭中，超过一半的病例 和/或卵巢癌。在零星的乳腺癌病例中， BRCA1在高级别导管癌中降低或检测不到，提示 这是乳腺癌病因学中的一种关键的肿瘤抑制因子。 一些实验室的研究表明，BRCA1在一种 路径的数量，我们的实验发现至少有三个独立的 与BRCA1相关的蛋白质复合体。该项目将确定 三个或更多含有BRCA1的蛋白质复合体的成分，确定 BRCA1中对与这些复合体结合至关重要的结构域，以及 识别对BRCA1转录功能至关重要的结构域，DNA 修复和抑制生长。通过这种方式，这些实验将相互关联 BRCA1蛋白结构域与蛋白质复合体和功能效应的关系。自.以来 BRCA1是一种多功能蛋白质，对其进行剖析是至关重要的 每个功能所需的域。这样结构-功能评估然后可以 用于确定关键的肿瘤抑制活性(活性) BRCA1.本项目将阐明BRCA1作为一种 肿瘤抑制因子，它将阐明乳房和卵巢的特异性 BRCA1突变。

DESCRIPTION: (provided by applicant) Breast cancer is associated with the loss of function of tumor suppressor proteins as well as the activation of oncogenes. About 4 percent of all breast cancer cases are associated with the inheritance of mutations at the BRCA1 gene. The BRCA1 gene carries mutations in over half of the cases among families with increased occurrence of breast and/or ovarian cancer. Among sporadic cases of breast cancer, expression of BRCA1 is reduced or undetectable in high grade ductal carcinomas, suggesting that this is a critical tumor suppressor in the etiology of breast cancer. Research in a number of laboratories has indicated that BRCA1 functions in a number of pathways, and our experiments have identified at least three separate protein complexes with which BRCA1 associates. This project will identify components of the three, or more, BRCA1-containing protein complexes, identify domains in BRCA1 which are critical for association with these complexes, and identify domains which are critical for BRCA1 function in transcription, DNA repair, and growth suppression. In this way, these experiments will correlate BRCA1 protein domains to protein complexes and to functional effects. Since BRCA1 is a multifunctional protein, it is critical to dissect the protein domains required for each function. Such structure-function evaluation can then be applied into identifying the key tumor suppressor activity (activities) of BRCA1. This project will clarify key factors in the function of BRCA1 as a tumor suppressor, and it will shed light on the breast and ovarian specificity of BRCA1 mutation.