FASEB SRC on Ubiquitin and Cellular Regulation

描述(由申请人提供)：FASE B泛素和细胞调节夏季研究会议是该领域关于泛素-蛋白酶体系统的基础生物化学和生物功能的主要论坛。该会议自1989年以来每两年举行一次，一直在佛蒙特州学院举行，并一直得到FASE B的支持。本申请寻求对今后三次会议(2012、2014、2016)的支持。泛素的生物学功能需要它与细胞蛋白的共价结合，而研究最深入的结果是26S蛋白酶体的降解。最近的发现已经开始揭示泛素激活和结合反应的结构基础，以及将目标蛋白转移到蛋白酶体中进行降解的复杂步骤。了解这些过程是至关重要的，因为泛素系统选择性地降解蛋白质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、发育和抗原处理。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、神经系统和代谢性疾病。除了作为降解信号外，泛素化还在蛋白质运输和信号传递中具有非蛋白水解性功能，这一方面的途径对于涉及天然免疫系统中的膜受体和信号的过程至关重要。除了泛素本身，还有几种泛素样蛋白通过平行的生化途径连接在一起，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。这些途径在传染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，细胞通过特定的泛素样蛋白保护自己免受感染。2012年会议将于6月24日至29日举行，组织者为Jon Huibregtse(Univ.德克萨斯州)和兰迪·汉普顿(加州大学圣地亚哥分校)。会议将首先由Dan Finley博士(哈佛医学院)作主旨发言，随后将举行九次科学会议，每次会议由实地领导人(5名女性，4名男性)主持。到目前为止，已确认28名国际知名发言者(16名妇女，2名少数民族)。将从摘要中再选出大约10名发言者，我们将继续寻求这些发言者和与会者之间的多样性。总体而言，我们寻求在这一动态领域加强新的和令人兴奋的发现的传播，这将扩大我们对泛素、蛋白酶体和泛素样蛋白在健康和疾病中的作用的理解。 与公共卫生相关：这次会议将集中讨论蛋白质泛素化、蛋白质周转和泛素相关蛋白质修饰在许多疾病状态中的重要性，包括癌症、神经和发育疾病，以及病毒和微生物传染病。我们预计，在识别调节泛素/Ub1途径酶和蛋白酶体活性的药理学试剂方面将出现令人兴奋的进展。

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.