SUMO suppresses and MYC amplifies transcription globally by regulating CDK9 sumoylation  

作　　者：Fang Yu Guang Shi Shimeng Cheng Jiwei Chen Shwu-Yuan Wu Zhiqiang Wang Nansong Xia Yunhao Zhai Zhenxing Wang Yu Peng Dong Wang James X. Du Lujian Liao Sheng-Zhong Duan Tieliu Shi Jinke Cheng Cheng-Ming Chiang Jiwen Li Jiemin Wong 

机构地区：[1]Shanghai Key Laboratory of Regulatory Biology, Fengxian District Central HospitaI-ECNU Joint Center of Translational Medicine, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China [2]Simmons Comprehensive Cancer Center, Department of Biochemistry, and Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA [3]Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China [4]Laboratory of Oral Microbiology, Shanghai Research Institute of Stomatology, Shanghai Key Laboratory of Stomatology, Ninth People's Hospital, School of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China [5]Spresent address: Key Laboratory of Gene Engineering of the Ministry of Education and Institute of Healthy Aging Research, School of Life Sciences, Sun Yat-sen University,Guangzhou 510275, China

出　　处：《Cell Research》2018年第6期670-685,共16页细胞研究（英文版）

摘　　要：Regulation of transcription is fundamental to the control of cellular gene expression and function. Although recent studies have revealed a role for the oncoprotein MYC in amplifying global transcription, little is known as to how the global transcription is suppressed. Here we report that SUMO and MYC mediate opposite effects upon global transcription by controlling the level of CDK9 sumoylation. On one hand, SUMO suppresses global transcription via sumoylation of CDK9, the catalytic subunit of P-TEFb kinase essential for productive transcriptional elongation. On the other hand, MYC amplifies global transcription by antagonizing CDK9 surnoylation. Sumoylation of CDK9 blocks its interaction with Cyclin TI and thus the formation of active P-TEFb complex. Transcription profiling analyses reveal that SUMO represses global transcription, particularly of moderately to highly expressed genes and by generating a sumoylation-resistant CDK9 mutant, we confirm that sumoylation of CDK9 inhibits global transcription. Together, our data reveal that SUMO and MYC oppositely control global gene expression by regulating the dynamic sumoylation and desumoylation of CDK9.

关 键 词：压制 放大 调整 球性 CYCLIN 相互作用 控制 基因 

分 类 号：Q421[生物学—神经生物学] TQ456.04[生物学—生理学]