Third International Mdm2 Workshop

具体目标：为第三届国际MDM 2会议获得部分资金，使年轻的美国学员（研究生和博士后）和美国演讲者参加会议。 科学描述：MDM 2蛋白是肿瘤抑制蛋白p53的主要负调节因子。MDM 2是一种p53特异性E3泛素脂肪酶，通过26 S蛋白酶体途径介导p53降解，从而使未应激细胞中的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-MDM 2复合物，从而在应激反应期间快速稳定p53水平。 因此，p53-MDM 2复合物的小分子抑制剂对于在保留野生型p53（约50%）的肿瘤中开发新的癌症疗法具有很大的希望，并且正在由学术实验室以及一些主要的制药公司大力开发。 相反，通过各种方式扩增MDM 2表达及其同源物MDMX是抑制p53肿瘤抑制作用的致癌途径，并且在许多人类肿瘤中实现。 与会者：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150-180名国际科学家出席会议。 目标：迄今为止，已经举行了两次专门讨论这一迅速发展领域的国际MDM 2会议。第三届MDM 2会议的议程是在肿瘤发生、p53肿瘤抑制、细胞周期控制和凋亡以及早期哺乳动物发育等更广泛领域的背景下讨论最新的MDM 2研究。另一个焦点将是MDM 2作为合理的药物靶点。 在这方面，一些受邀发言者将来自从事此类药物研究的制药业。 讨论的主题：MDM 2的结构和功能，MDM 2上游的应激信号传导：通过翻译后修饰调节MDM 2，通过蛋白质-蛋白质相互作用调节MDM 2功能，MDM 2家族成员，动物模型和临床关联，作为治疗靶点的MDM 2蛋白，其他p53泛素脂肪酶和p53去泛素化酶。

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.