Identifizierung und Charakterisierung von Proteinen, welche die Stabilität und Funktionalität des anti-apoptotische Bcl-2 Mitglieds A1/Bfl-1 regulieren

细胞程序性死亡（凋亡）的失调是使细胞转化为癌细胞的谜团之一。肿瘤细胞凋亡失调的机制之一是抗凋亡Bcl-2蛋白的过度表达。A1/Bfl-1是其中一种蛋白质。我们发现，定义不明确的E3泛素连接酶（hecd1）直接与A1/Bfl-1相互作用并控制其数量。由于hector 1与已知的肿瘤抑制因子HACE1相关，它可能调节细胞的存活和增殖，从而干扰恶性转化。我们提出了一种双重方法来阐述hector 1的功能：在分子上，我们想要定义hector 1复合物的成分，在细胞上，我们打算在两种突变动物模型中研究hector 1缺乏对B细胞和T细胞的影响。通过这种结合的方法，我们将提高我们对两种潜在危险蛋白A1/Bfl-1和hector -1的基本了解，从而为最终干扰它们在癌症中的失调奠定基础。

Dysregulation of programmed cell death (apoptosis) is one piece of the puzzle allowing cells to trans-form into cancer cells. One mechanism of apoptosis dysregulation in cancer is overexpression of anti-apoptotic Bcl-2 proteins. A1/Bfl-1 is one of these proteins. We have found that the poorly defined E3 ubiquitin ligase, HECTD1, directly interacts with and controls the amount of A1/Bfl-1. As HECTD1 is related to the known tumor suppressor HACE1, it might regulate survival and proliferation of cells thereby interfering with malignant transformation. We propose a twofold approach to elaborate the function of HECTD1:molecularly, we want to define the components of the HECTD1 complex, and cellularly, we intend to examine the effect of HECTD1-deficiency on B and T cells in two mutant animal models. With this combined approach we will improve our basic understanding of two potentially hazardous proteins A1/Bfl-1 and HECTD1, thereby laying the groundwork toward eventually interfering with their dysregulation in cancer.