Mechanism of the RalGAP tumor suppressor complex

RalGAP肿瘤抑制复合物的机制

• 批准号: 503189408
• 负责人: Professor Dr. Daniel Kümmel
• 金额: --
• 依托单位: Institut für Biochemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/503189408?language=en
• 关键词: Mechanism; RalGAP; tumor; suppressor; complex

The small GTPases of the Ral family represent a crucial hub in the coordination of a variety of intracellular trafficking and signaling pathways. Rals are involved in the control of proliferation and survival, regulated exocytosis, endocytosis and autophagy. Because they have been implicated in the development of disease, primarily cancer, but also metabolic syndrome, Rals have received significant attention and are targeted for drug development. Much of the molecular mechanisms that underlie the function of Ral GTPases, however, remain elusive. This also applies to the RalGAP (Ral GTPase activating protein) complexes that act as key negative regulators of Ral GTPases and are therefore described as tumor suppressor proteins. Many of the molecular aspects underlying RalGAP function, like catalytic mechanism, activation and localization, and the contributions of most parts of these large complexes to these processes are not understood. We thus propose the structural und mechanistic characterization of RalGAP complex to gain novel insight into their role in the regulation of Ral GTPase and their contribution to the development of disease.

Ral家族的小GTP酶代表了协调各种细胞内运输和信号传导途径的关键枢纽。Rals参与控制增殖和存活，调节胞吐、胞吞和自噬。因为它们与疾病的发展有关，主要是癌症，但也与代谢综合征有关，所以Rals受到了极大的关注，并成为药物开发的目标。然而，Ral GTP酶功能的许多分子机制仍然难以捉摸。这也适用于RalGAP（Ral GTP酶激活蛋白）复合物，其充当Ral GTP酶的关键负调节剂，因此被描述为肿瘤抑制蛋白。RalGAP功能背后的许多分子方面，如催化机制，活化和定位，以及这些大复合物的大部分对这些过程的贡献尚不清楚。因此，我们提出了RalGAP复合物的结构和机制表征，以获得新的见解，他们的作用，在调节Ral GTP酶和疾病的发展作出贡献。