题目：应激下的泛素与类泛素分子
主讲人：Dr. Dimitris Xirodimas, 法国大分子与生化研究中心(CRBM)
时间：2012年9月4日14:30
地点：医学楼4楼402栋2400会议室
欢迎广大师生踊跃参加！
医学部欧洲杯官网
2012.8.30
附：
Dr. Dimitris Xirodimas
摘要：泛素（ubiquitin）与类泛素分子（如NEDD8和SUMO）参与的转译后修饰是蛋白功能调控的重要机制。越来越多的证据显示，泛素化与类泛素化几乎参与了细胞内所有的生理过程，包括：蛋白质降解、转录活性调控、细胞内定位、DNA修复、内吞作用、信号传导、自噬等等。我的研究重点是泛素与类泛素NEDD8对转录活性和细胞生长的调控。对蛋白稳定性和功能的重要性使得这些途径成为药物开发的主要标靶。泛素-蛋白酶体抑制剂已经应用于治疗多发骨髓瘤和淋巴瘤，而NEDD8抑制剂已经在临床试验。
Title: Ubiquitin-like molecules under stress
Speaker: Dr. Dimitris Xirodimas, Research Center on Macromolecules Biochemistry (CRBM), France
Time: 14:30, 4th September, 2012
Place: 4th floor meeting room
Host: Dr. Geng Liu
Abstract: Post-translational modifications of proteins with ubiquitin and ubiquitin-like molecules (Ubls) such as SUMO and NEDD8 are critical mechanisms of protein function regulation. It is now believed that these pathways are involved in the control of almost every biological process in the cell, from protein destruction to regulation of transcriptional activity, subcellular localisation, DNA repair, endocytosis, signal transduction and autophagy. My research focuses on the role of ubiquitin and the ubiquitin-like (Ubl) molecule NEDD8 in the regulation of transcriptional activity and cell growth. These pathways have emerged as key regulators of protein stability and function and are major targets for Pharmaceutical companies for therapeutic intervention. Inhibitors of the ubiquitin-proteasome pathway are used for the treatment of multiple myeloma and mantle cell lymphoma, whereas inhibitors of the NEDD8 pathway are in clinical trials.
Selected publications
Leidecker O, Matic I, Mahata B, Pion E, XirodimasDP (2012) The ubiquitin E1 enzyme Ube1 mediates NEDD8 activation under diverse stress conditions.Cell Cycle 11(6):1142-50.
Mahata B, Sundqvist A and Xirodimas DP. (2011). Recruitment of L11RP at promoter sites of p53-regulated genes upon nucleolar stress through NEDD8 and MDM2 dependent manner. Oncogene 31(25):3060-71.
Alexandru G, Pariente N and Xirodimas DP. In the family with ubiquitin. (2011). EMBO reports 12(9):880-2.
Liu, G and Xirodimas DP (2010). NUB-1 controls the localization of p53 through co-operation of the NEDD8 and ubiquitin pathways. Oncogene 29(15):2252-61.
Tatham MH, Rodriguez MS, Xirodimas DP and Hay RT(2009). Detection of protein SUMOylation in vivo. Nature protocols; 4(9):1362-71.
Sundqvist A, Liu G, Mirsaliotis A and Xirodimas DP (2009). Regulation of nucleolar signaling to p53 through NEDDylation of L11. EMBO reports;10(10):1132-9.
Xirodimas DP*, Sundqvist A, Nakamura A, Shen L, Botting C and Ronald T. Hay (2008). Ribosomal proteins are targets for the NEDD8 pathway. EMBO reports; 9(3):280-6. * corresponding author
Xirodimas DP, Saville MK, Bourdon JC, Hay RT, Lane DP (2004). MDM2-mediated NEDD8 conjugation of p53 inhibits its transcriptional activity. Cell. ; 118(1):83-97.
Xirodimas DP, Saville MK, Edling C, Lane DP and Lain S. (2001). Different effects of p14ARF on the levels of ubiquitinated p53 and MDM2 in vivo.Oncogene 20(36):4972-83.