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

^*Corresponding author for this work

Department of Physics

Research output: Contribution to journal › Article › peer-review

135 Citations (Scopus)

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.

Original language	English
Pages (from-to)	62-74
Number of pages	13
Journal	Molecular Cell
Volume	42
Issue number	1
DOIs	https://doi.org/10.1016/j.molcel.2011.02.022
Publication status	Published - 2011 Apr 8

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/j.molcel.2011.02.022

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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, vol. 42, no. 1, pp. 62-74. https://doi.org/10.1016/j.molcel.2011.02.022

@article{2dde528fe95e4db188c1085453a63499,

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",

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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

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

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

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

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