Targeted Protein Degradation: From Small Molecules to Complex Organelles

摘要 要求支持一个Keystone专题讨论会，题为“靶向蛋白质降解：从小 分子到复杂的细胞器，由Sascha Martens，Tim Clausen和Judith Frydman博士组织。的 会议将于2021年6月6日至9日在奥地利维也纳举行。 靶向蛋白质降解在调节几乎所有细胞功能中起关键作用，因此，其 功能障碍与严重的病理学有关，包括癌症、神经变性和衰老等疾病， 相关疾病。因此，对蛋白质清除途径的基本见解可能会被利用， 用于治疗多种疾病。虽然在揭示人类的 自噬机制和泛素-蛋白酶体系统，主要的蛋白质降解途径 到目前为止，尽管这些领域相互关联，但它们仍然相互隔离。 流程.这种分离现在导致迫切需要讨论这些途径的相互作用， 分子和细胞水平，以整合我们对这些过程的理解，以及它们如何有助于 疾病病理学这次会议将汇集来自这些不同领域的研究人员，他们不 通常相互作用，以建立蛋白质降解的整体和综合愿景。这样一个综合 会议强调蛋白质降解研究的不同分支之间的联系， 目前还不存在，所以这次Keystone研讨会会议将是第一次重塑这些领域如何 互动和合作，对基础科学和疾病过程产生变革性的见解。主题 讨论的内容包括：（1）底物识别和能量依赖性蛋白酶加工，自噬 （2）将蛋白质靶向不同降解途径的信号;（3） 蛋白水解系统和伴侣蛋白途径;（4）用小分子重编程降解， 治疗应用;（5）降解程序驱动全球蛋白质组重塑。与会者将 接触新的观点，以及方法，技术和方法，这将推动研究 在他们的领域内，以及蛋白质降解景观中的许多不同组成部分。

ABSTRACT Support is requested for a Keystone Symposia conference entitled Targeted Protein Degradation: From Small Molecules to Complex Organelles, organized by Drs. Sascha Martens, Tim Clausen and Judith Frydman. The conference will be held in Vienna, Austria from June 6-9, 2021. Targeted protein degradation plays a critical role in regulating nearly all cellular functions, and as such, its dysfunction is associated with severe pathologies including diseases like cancer, neurodegeneration and age- associated diseases. Therefore, fundamental insights into protein clearance pathways might be harnessed for therapeutic applications against a wide range of diseases. While much progress has been made in revealing mechanisms of autophagy and the ubiquitin-proteasome system, the major protein degradation pathways defined thus far, these fields continue to remain isolated from each other despite the interconnection of these processes. This separation is now leading to an urgent need to discuss the interplay of these pathways at the molecular and cellular levels to integrate our understanding of these processes and how they contribute to disease pathology. This conference will bring together researchers from these different fields, who do not typically interact, to build a holistic and integrated vision of protein degradation. Such an integrative conference highlighting the connections between the different branches of protein degradation research does not yet exist, so this Keystone Symposia conference will be the first of its kind to reshape how these fields interact and collaborate to yield transformative insights into both basic science and disease processes. Topics of discussion will include: (1) Substrate recognition and processing by energy-dependent proteases, autophagy and lysosomal pathways; (2) Signals targeting proteins to distinct degradation pathways; (3) Interplay between proteolytic systems and chaperone pathways; (4) Reprogramming degradation with small molecules for therapeutic applications; (5) Degradation programs driving global proteome remodeling. Attendees will be exposed to novel perspectives, as well as methods, techniques and approaches, that will advance research within their field, and across the many different components in the protein degradation landscape.