Third International Mdm2 Workshop

描述(由申请人提供)：具体目标：获得第三届国际MDM2会议的部分资金，使年轻的美国实习生(研究生和博士后)和美国演讲者能够参加会议。 科学描述：MDM2蛋白是肿瘤抑制蛋白P53的主要负调控因子。MDM2是一种p53特异的E3泛素脂肪酶，通过26S蛋白酶体途径介导p53的降解，从而使非应激细胞中的p53水平保持在非常低的水平。应激诱导的P53翻译后修饰破坏P53-MDM2复合体，从而在应激反应中迅速稳定P53水平。因此，P53-MDM2复合体的小分子抑制剂在保留野生型P53(约50%)的肿瘤中开发新的癌症治疗方法具有很大的前景，学术实验室和一些主要制药公司正在大力开发。相反，通过各种手段扩增MDM2及其同源基因MDMX是一种抑制P53抑瘤作用的致癌途径，在许多人类肿瘤中都存在。 参与者：来自美国、加拿大、欧洲、英国、以色列和亚洲的约25-30名科学家将发表演讲，介绍他们的最新发现。根据以往的出席情况，我们预计将有150至180名国际科学家参加会议。 目标：迄今已举行了两次国际MDM2会议，专门讨论这一快速增长的领域。第三届MDM2会议的议程是在肿瘤发生、p53肿瘤抑制、细胞周期控制和细胞凋亡以及哺乳动物早期发育等更广泛领域的背景下讨论最新的MDM2研究。另一个焦点将是MDM2作为合理的药物靶点。 在这方面，一些受邀的发言者将来自从事此类药物工作的制药业。 主题包括：MDM2的结构和功能，MDM2上游的压力信号：翻译后修饰对MDM2的调节，蛋白质-蛋白质相互作用对MDM2功能的调节，MDM2家族成员，动物模型和临床联系，作为治疗靶点的MDM2蛋白，其他P53泛素脂肪酶和P53脱泛素酶。

DESCRIPTION (provided by applicant): Specific Objective: To obtain partial funding for the 3rd International MDM2 Meeting to enable young US trainees (graduate students and post docs) and US speakers to attend the meeting. Scientific Description: The MDM2 protein is the principal negative regulator of the tumor suppressor protein p53. MDM2, a p53-specific E3 ubiquitin lipase, mediates p53 degradation via the 26S proteasome pathway, thus keeping p53 levels in unstressed cells very low. Stress-induced posttranslational modifications of p53 disrupt the p53-MDM2 complex, thereby rapidly stabilizing p53 levels during a stress response. Accordingly, small molecule inhibitors of the p53-MDM2 complex hold great promise for development of novel cancer therapies in tumors that retain wild type p53 (about 50%) and are being vigorously developed by academic laboratories as well as by some major pharmaceutical companies. Conversely, amplification of MDM2 expression and its homolog MDMX by various means is an oncogenic pathway that suppresses the p53 tumor suppressive action and is realized in many human tumors. Participants: About 25-30 scientists from the USA, Canada, Europe, UK, Israel and Asia will give talks to present their latest findings. Based on previous attendances, we anticipate that 150-180 international scientists will attend the Meeting. Goals: Two International MDM2 Meetings dedicated to this rapidly growing field have been held to date. The agenda for the 3rd MDM2 Meeting is to discuss the newest MDM2 research in the context of the broader fields of tumor genesis, p53 tumor suppression, cell cycle control and apoptosis, and early mammalian development. Another focus will be MDM2 as a rational drug target. In this regard, a few invited speakers will be from the pharmaceutical industry working on such drugs. Topics convered: Structure and Function of MDM2, Stress Signaling Upstream of MDM2: Regulation of MDM2 by Posttranslational Modifications, Regulation of MDM2 function by Protein-Protein interactions, MDM2 Family members, Animal Models and Clinical Associations, Mdm2 proteins as therapeutic targets, other p53 Ubiquitin lipases and p53 Deubiquitylase.