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

doi:10.1016/j.molcel.2011.02.022

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

^*此作品的通信作者

物理學系

研究成果: 雜誌貢獻 › 期刊論文 › 同行評審

134 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
卷	42
發行號	1
DOIs	https://doi.org/10.1016/j.molcel.2011.02.022
出版狀態	已發佈 - 2011 4月 8

ASJC Scopus subject areas

分子生物學
細胞生物學

存取文件

10.1016/j.molcel.2011.02.022

其它文件與鏈接

Phosphorylation of SUMO-interacting motif by CK2 enhances Daxx SUMO binding activity
Chang, C. (Contributor), Naik, M. T. (Contributor), Huang, Y. (Contributor), Jeng, J. (Contributor), Liao, P. (Contributor), Kuo, H. (Contributor), Ho, C. (Contributor), Hsieh, Y. (Contributor), Lin, C. (Contributor), Huang, N. (Contributor), Naik, N. M. (Contributor), Kung, C. C. (Contributor), Lin, S. (Contributor), Chen, R. (Contributor), Chang, K. (Contributor), Huang, T. (Contributor) & Shih, H. (Contributor), Protein Data Bank (PDB), 2010 12月 1
DOI: 10.2210/pdb2KQS/pdb, https://www.wwpdb.org/pdb?id=pdb_00002kqs
資料集: Dataset

引用此

Chang, C. C., Naik, M. T., Huang, Y. S., Jeng, J. C., Liao, P. H., Kuo, H. Y., Ho, C. C., Hsieh, Y. L., Lin, C. H., Huang, N. J., Naik, N. M., Kung, C. C. H., Lin, S. Y., Chen, R. H., Chang, K. S., Huang, T. H., & Shih, H. M. (2011). Structural and Functional Roles of Daxx SIM Phosphorylation in SUMO Paralog-Selective Binding and Apoptosis Modulation. Molecular Cell, 42(1), 62-74. https://doi.org/10.1016/j.molcel.2011.02.022

Chang, CC, Naik, MT, Huang, YS, Jeng, JC, Liao, PH, Kuo, HY, Ho, CC, Hsieh, YL, Lin, CH, Huang, NJ, Naik, NM, Kung, CCH, Lin, SY, Chen, RH, Chang, KS, Huang, TH & Shih, HM 2011, 'Structural and Functional Roles of Daxx SIM Phosphorylation in SUMO Paralog-Selective Binding and Apoptosis Modulation', Molecular Cell, 卷 42, 編號 1, 頁 62-74. https://doi.org/10.1016/j.molcel.2011.02.022

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

abstract = "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.",

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

note = "Funding Information: We thank Jorge Allende, Linda M Boxer, and Zhengxin Wang for pcEFL-HA-CK2α, Bcl-2 , and c-FLIP luciferase reporter constructs, respectively, Michael Matunis and Xiang-Dong Zhang for SUMO-2/3 antibody, and the NRPGM Core Facility for NMR, Proteomics and RNAi by providing High-Field NMR, LTQ-Orbitrap mass spectrometry and lentivirus constructs for shRNAs of CK2-α and GFP, respectively, and Silvia R. da Costa for editing. The work was supported by the NSC98-2113-M-001-014 and NHRI-EX99-9933B1 grants to T.-H.H. and NSC Frontier Grant (NSC98-2321-B-001-012), NSC99-3112-B-001-010, and an Academia Sinica Investigator Award to H.-M.S. ",

year = "2011",

month = apr,

day = "8",

doi = "10.1016/j.molcel.2011.02.022",

language = "English",

volume = "42",

pages = "62--74",

journal = "Molecular Cell",

issn = "1097-2765",

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TY - JOUR

T1 - Structural and Functional Roles of Daxx SIM Phosphorylation in SUMO Paralog-Selective Binding and Apoptosis Modulation

AU - Chang, Che Chang

AU - Naik, Mandar T.

AU - Huang, Yen Sung

AU - Jeng, Jen Chong

AU - Liao, Pei Hsin

AU - Kuo, Hong Yi

AU - Ho, Chun Chen

AU - Hsieh, Yung Lin

AU - Lin, Chiou Hong

AU - Huang, Nai Jia

AU - Naik, Nandita M.

AU - Kung, Camy C.H.

AU - Lin, Shu Yu

AU - Chen, Ruey Hwa

AU - Chang, Kun Sang

AU - Huang, Tai Huang

AU - Shih, Hsiu Ming

N1 - Funding Information: We thank Jorge Allende, Linda M Boxer, and Zhengxin Wang for pcEFL-HA-CK2α, Bcl-2 , and c-FLIP luciferase reporter constructs, respectively, Michael Matunis and Xiang-Dong Zhang for SUMO-2/3 antibody, and the NRPGM Core Facility for NMR, Proteomics and RNAi by providing High-Field NMR, LTQ-Orbitrap mass spectrometry and lentivirus constructs for shRNAs of CK2-α and GFP, respectively, and Silvia R. da Costa for editing. The work was supported by the NSC98-2113-M-001-014 and NHRI-EX99-9933B1 grants to T.-H.H. and NSC Frontier Grant (NSC98-2321-B-001-012), NSC99-3112-B-001-010, and an Academia Sinica Investigator Award to H.-M.S.

PY - 2011/4/8

Y1 - 2011/4/8

N2 - 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.

AB - 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.

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

摘要

ASJC Scopus subject areas

存取文件

其它文件與鏈接

指紋

資料集

Phosphorylation of SUMO-interacting motif by CK2 enhances Daxx SUMO binding activity

引用此