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

• Applicant: Privatdozent Dr. Ingolf Berberich
• Subject Area: Cell Biology
• Term: from 2007 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 37863842

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.

• DFG Programme: Research Grants