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

调节抗凋亡 Bcl-2 成员 A1/Bfl-1 稳定性和功能的蛋白质的鉴定和表征

• 批准号: 37863842
• 负责人: Privatdozent Dr. Ingolf Berberich
• 金额: --
• 依托单位: Institut für Virologie und Immunbiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/37863842?language=en
• 关键词: Identifizierung; und; Charakterisierung; von; Proteinen

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.

程序性细胞死亡(细胞凋亡)的失调是使细胞转化为癌细胞的谜题之一。肿瘤细胞凋亡失调的机制之一是抗细胞凋亡的Bcl2蛋白过度表达。A1/BFL-1就是其中的一种。我们发现，定义不佳的E3泛素连接酶HECTD1直接与A1/BFL-1相互作用并控制其数量。由于HECTD1与已知的肿瘤抑制因子HACE1有关，它可能调节细胞的存活和增殖，从而干扰恶性转化。我们提出了两种方法来阐述HECTD1的功能：在分子上，我们想要定义HECTD1复合体的组成；在细胞上，我们打算在两个突变的动物模型中检测HECTD1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质A1/BFL-1和HECTD1的基本理解，从而为最终干预它们在癌症中的失调奠定基础。