FASEB SRC on Ubiquitin and Cellular Regulation

描述（由申请人提供）：FASEB关于泛素和细胞调节的夏季研究会议是泛素-蛋白酶体系统的基本生物化学和生物功能领域的首要论坛。自1989年以来，该会议每两年举行一次，始终在佛蒙特学院举行，并始终得到FASEB的支持。该申请寻求对未来三次会议（2012年，2014年，2016年）的支持。泛素的生物学功能需要其共价连接到细胞蛋白质，并且对此研究最多的结果是被26 S蛋白酶体降解。最近的发现已经开始揭示泛素活化和缀合反应的结构基础，以及将靶蛋白转运到蛋白酶体中进行降解所涉及的复杂步骤。了解这些过程是至关重要的，因为泛素系统对蛋白质的选择性降解是控制真核细胞生物学几乎所有方面的机制，包括细胞周期，转录，代谢途径，发育和抗原加工。此外，该系统的缺陷或过度激活涉及许多疾病过程，特别是癌症、神经系统和代谢疾病。除了作为降解信号起作用之外，泛素化在蛋白质运输和信号传导中具有非蛋白水解功能，并且该途径的这一方面对于涉及先天免疫系统中的膜受体和信号传导的过程至关重要。除了泛素本身，还有几种泛素样蛋白通过平行的生物化学途径结合，这些蛋白的生物学功能的表征是一个非常活跃的发现领域。这些途径在感染性疾病中也是至关重要的，因为现在很明显，微生物编码泛素样蛋白，细菌和病毒产生酶来调节宿主细胞中的细胞泛素化途径，并且细胞用特定的泛素样蛋白来防御感染因子。2012年的会议将于6月24日至29日举行，组织者是乔恩·惠布雷格茨（德克萨斯大学）和兰迪·汉普顿（加州大学圣地亚哥分校）。会议将以Dan Finley博士（哈佛医学院）的主旨演讲开始开始，随后将举行九次科学会议，每次会议由该领域的领导人主持（5名女性，4名男性）。到目前为止，已经确认了28位国际知名演讲者（16位女性，2位少数民族）。将从摘要中选出大约10名发言者，我们将继续在这些发言者和与会者中寻求多样性。总的来说，我们寻求加强传播新的和令人兴奋的发现在这个充满活力的领域，这将扩大我们的泛素，蛋白酶体和泛素样蛋白在健康和疾病中的作用的理解。 公共卫生相关性：本次会议将重点讨论蛋白质泛素化，蛋白质周转和泛素相关蛋白在许多疾病状态中的修饰的重要性，包括癌症，神经和发育疾病，以及病毒和微生物感染性疾病。我们预计，令人兴奋的发展将提出的药理学试剂，调节泛素/Ubl途径酶和蛋白酶体的活动的鉴定。

DESCRIPTION (provided by applicant): The FASEB Summer Research Conference on Ubiquitin and Cellular Regulation is the premier forum for the field on the fundamental biochemistry and biologic functions of the ubiquitin-proteasome system. This conference has been held biannually since 1989, always at Vermont Academy, and always supported by FASEB. This application seeks support for the next three conferences (2012, 2014, 2016). The biological functions of ubiquitin require its covalent attachment to cellular proteins, and the best-studied consequence of this is degradation by the 26S proteasome. Recent discoveries have begun to reveal the structural basis for ubiquitin activation and conjugation reactions, as well as the complex steps involved in translocating target proteins into the proteasome for degradation. Understanding these processes is critical, as the selective degradation of proteins by the ubiquitin system is a mechanism for control of virtually all aspects of eukaryotic cell biology, including the cell cycle, transcription, metabolic pathways, development, and antigen processing. Furthermore, defects or hyperactivation of the system is involved in many disease processes, particularly cancer, neurologic, and metabolic diseases. In addition to functioning as a degradation signal, ubiquitination has non- proteolytic functions in protein trafficking and signaling, and this aspect of the pathway is critical for processes that involve membrane receptors and signaling in the innate immune system. Beyond ubiquitin, itself, there are several ubiquitin-like proteins that are conjugated through parallel biochemical pathways, and the characterization of the biologic functions of these proteins is a very active area of discovery. These pathways are also critical in infectious diseases, as it is now evident that microbes encode ubiquitin-like proteins, that bacteria and viruses produce enzymes to modulate cellular ubiquitination pathways in host cells, and that cells defend themselves against infectious agents with specific ubiquitin-like proteins. The 2012 meeting will be held from June 24-29, and the organizers are Jon Huibregtse (Univ. of Texas) and Randy Hampton (UC-San Diego). The conference will begin with a key-note presentation by Dr. Dan Finley (Harvard Medical School), and will be followed by nine scientific sessions covering, each chaired by leaders in field (5 women, 4 men). So far, 28 internationally renowned speakers have been confirmed (16 women, 2 minorities). Approximately 10 additional speakers will be chosen from abstracts, and we will continue to seek diversity among these speakers and among attendees, in general. Overall, we seek to enhance the dissemination of new and exciting findings in this dynamic field, which will broaden our understanding of the roles of ubiquitin, the proteasome, and ubiquitin-like proteins in health and disease. PUBLIC HEALTH RELEVANCE: This conference will be focused on the importance of protein ubiquitylation, protein turnover, and modification by ubiquitin-related proteins in many disease states, including cancer, neurologic and developmental diseases, and viral and microbial infectious diseases. We anticipate that exciting developments will be presented on the identification of pharmacologic agents that modulate the activities of ubiquitin/Ubl pathway enzymes and the proteasome.