Ubiquitin/Cancer:Molecular Targets/Mechanisms to Clinic

描述（由申请人提供）：本提案的目的是组织一次题为“泛素和癌症：从分子靶点和机制到临床”的会议，会议定于2006年1月18日至22日在佛罗里达布埃纳维斯塔湖的迪士尼当代度假村举行。 本次会议在蛋白质泛素化领域的其他会议中是独一无二的，因为它具有强大的临床/翻译组成部分（占所有演讲的1/3），包括有机会回顾蛋白酶体抑制剂在临床治疗癌症方面的最新成功，以及验证泛素连接酶抑制剂用于癌症治疗的临床前研究。因此，与UPS的其他计划会议几乎没有重叠，因为UPS的计划更集中，涉及细胞生物学过程和将涵盖的疾病。 具体来说，会议的目标是：1）提供蛋白质泛素化领域的概述，包括审查和讨论UPS介导的各种细胞过程的调节，这些过程与癌症有关; 2）促进讨论UPS在恶性肿瘤中的作用和治疗干预的机会（药物靶点）; 3）评估现有的以及提出的干扰UPS的治疗方法的成功和局限性; 4）为癌症科学家和蛋白质泛素化领域的专家之间的互动提供论坛; 5）为年轻科学家和其他对癌症和UPS领域感兴趣的人的教育做出贡献。 蛋白质泛素化和降解领域在过去十年中经历了爆炸性的增长。 UPS调节大量的生物过程，包括细胞周期、凋亡、蛋白质运输、信号传导、DMA复制和修复以及血管生成。因此，UPS中的缺陷已经与许多疾病直接相关。 去调节的蛋白质泛素化是癌症发展的主要促成因素。众所周知的例子是各种癌症中泛素连接酶BRCA 1、Mdm 2、VHL和Skp 2的失调。 我们希望这次会议将促进对治疗机会、治疗方法和UPS在恶性肿瘤中的作用的广泛讨论。 重点将放在目标识别和验证以及药物开发方面的挑战。

DESCRIPTION (provided by applicant): The aim of this proposal is to organize a conference titled "Ubiquitin and Cancer: From Molecular Targets and Mechanisms to the Clinic" scheduled for January 18-22, 2006, at Disney's Contemporary Resort in Lake Buena Vista, Florida. This conference is unique among other meetings in the protein ubiquitylation field for its strong clinical/translational component (1/3 of all talks), including the opportunity to review the recent successes with proteasome.inhibitors in treating cancer in the clinic, as well as the pre-clinical studies validating ubiquitin ligase inhibitors for cancer therapy. Thus, there will be little overlap with other planned meetings on the UPS because of its more focused program, with respect both to the cell biology processes and to the disease that will be covered. Specifically, the meeting objectives are: 1) to provide an overview of the field of protein ubiquitylation, including review and discussion of the UPS-mediated regulation of various cellular processes that are relevant for cancer; 2) to foster discussions on the role of the UPS in malignancy and the opportunities for therapeutic intervention (drug targets); 3) to evaluate the successes and limitations of existing as well as proposed therapeutic approaches to interfere with the UPS; 4) to provide a forum for interaction among cancer scientists and experts in the field of protein ubiquitylation; 5) to contribute to the education of young scientists and others interested in the fields of cancer and the UPS. The field of protein ubiquitylation and degradation has experienced explosive growth in the past decade. The UPS regulates an enormous range of biological processes, including cell cycle, apoptosis, protein trafficking, signaling, DMA replication and repair, and angiogenesis. Consistently, defects in the UPS have already been directly implicated with many diseases. Deregulated protein ubiquitylation represents a major contributing factor for cancer development. Well known examples are the deregulation of the ubiquitin ligases BRCA1, Mdm2, VHL and Skp2 in various cancers. We expect that this meeting will foster extensive discussion on therapeutic opportunities, on therapeutic approaches and on the role of the UPS in malignancy. Emphasis will be given to the challenges involved in target identification and validation, and in drug development.