BRCA1 Function

描述：（由申请人提供）乳腺癌与丧失 肿瘤抑制蛋白的功能以及 致癌基因大约4%的乳腺癌病例与乳腺癌有关。 BRCA 1基因突变的遗传。BRCA 1基因携带突变， 在乳腺癌发病率增加的家庭中， 和/或卵巢癌。在散发性乳腺癌病例中， BRCA 1在高级别导管癌中减少或检测不到，提示 这是乳腺癌病因学中的一个重要肿瘤抑制因子。 许多实验室的研究表明，BRCA 1在一个细胞中起作用， 多种途径，我们的实验已经确定了至少三种不同的途径 与BRCA 1相关的蛋白质复合物。该项目将确定 三种或更多种含有BRCA 1的蛋白质复合物的组分， BRCA 1中与这些复合物结合的关键结构域， 鉴定在转录、DNA 修复和生长抑制。这样一来，这些实验就能将 BRCA 1蛋白结构域与蛋白质复合物和功能效应的关系。以来 BRCA 1是一种多功能蛋白，对其进行深入的研究具有重要意义 每个功能所需的域。这样的结构-功能评估可以 应用于确定关键的肿瘤抑制活性（活性）， BRCA1。该项目将阐明BRCA 1作为一种免疫调节因子的功能中的关键因素。 肿瘤抑制因子，它将揭示乳腺和卵巢特异性 BRCA 1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.