Structural and Functional Roles of Daxx SIM Phosphorylation in SUMO Paralog-Selective Binding and Apoptosis Modulation

Che Chang Chang, Mandar T. Naik, Yen Sung Huang, Jen Chong Jeng, Pei Hsin Liao, Hong Yi Kuo, Chun Chen Ho, Yung Lin Hsieh, Chiou Hong Lin, Nai Jia Huang, Nandita M. Naik, Camy C H Kung, Shu Yu Lin, Ruey Hwa Chen, Kun Sang Chang, Tai Huang Huang, Hsiu Ming Shih

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107 引文 斯高帕斯(Scopus)

摘要

Small ubiquitin-like modifier (SUMO) conjugation and interaction are increasingly associated with various cellular processes. However, little is known about the cellular signaling mechanisms that regulate proteins for distinct SUMO paralog conjugation and interactions. Using the transcriptional coregulator Daxx as a model, we show that SUMO paralog-selective binding and conjugation are regulated by phosphorylation of the Daxx SUMO-interacting motif (SIM). NMR structural studies show that Daxx 732E-I-I-V-L-S-D-S-D740 is a bona fide SIM that binds to SUMO-1 in a parallel orientation. Daxx-SIM is phosphorylated by CK2 kinase at residues S737 and S739. Phosphorylation promotes Daxx-SIM binding affinity toward SUMO-1 over SUMO-2/3, causing Daxx preference for SUMO-1 conjugation and interaction with SUMO-1-modified factors. Furthermore, Daxx-SIM phosphorylation enhances Daxx to sensitize stress-induced cell apoptosis via antiapoptotic gene repression. Our findings provide structural insights into the Daxx-SIM:SUMO-1 complex, a model of SIM phosphorylation-enhanced SUMO paralog-selective modification and interaction, and phosphorylation-regulated Daxx function in apoptosis.
原文英語
頁(從 - 到)62-74
頁數13
期刊Molecular Cell
42
發行號1
DOIs
出版狀態已發佈 - 四月 8 2011
對外發佈

ASJC Scopus subject areas

  • 分子生物學
  • 細胞生物學

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