Distinct functional modes of SUMOylation for retinoid X receptor alpha

被引：1

作者：

Lee, Wai-Ping ^{[1
]}

Jena, Sarita ^{[1
]}

Rodriguez, E. Patricia ^{[1
]}

O'Donovan, Sinead P. ^{[1
]}

Wagner, Carl ^{[2
]}

Jurutka, Peter W. ^{[2
]}

Thompson, Paul D. ^{[1
]}

机构：

[1] Univ Ulster, Sch Biomed Sci, Coleraine BT52 1SA, Londonderry, North Ireland

[2] Arizona State Univ, Sch Math & Nat Sci, Glendale, AZ 85306 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2015年 / 464卷 / 01期

关键词：

Retinoid X receptor; Transcription; SUMO; PIAS; MODIFIER SUMO MODIFICATION; TRANSCRIPTIONAL ACTIVITY; RXR; PHOSPHORYLATION; DEGRADATION;

D O I：

10.1016/j.bbrc.2015.06.115

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The present study investigated human retinoid X receptor alpha (hRXR alpha) as a substrate for modification with small ubiquitin like modifier (SUMO) and how members of the protein inhibitor of activated STAT (PIAS) family may impact upon this process. In agreement with a previous study, we validate Ubc9 to facilitate SUMOylation of hRXR alpha at lysine 108 but note this modification to occur for all isoforms rather than specifically with SUMO1 and to preferentially occur with the unliganded form of hRXR alpha. SUMOylation of hRXR alpha is significantly enhanced through PIAS4-mediated activity with lysine 245 identified as a specific SUMO2 acceptor site modified in a PIAS4-dependent fashion. While individual mutations at lysine 108 or 245 modestly increase receptor activity, the combined loss of SUMOylation at both sites significantly potentiates the transcriptional responsiveness of hRXR alpha suggesting both sites may cooperate in a DNA element-dependent context. Our findings highlight combinatorial effects of SUMOylation may regulate RXR alpha-directed signalling in a gene-specific fashion. (C) 2015 Elsevier Inc. All rights reserved.

引用

页码：195 / 200

页数：6

共 18 条

[1] Control of nuclear receptor activities in metabolism by post-translational modifications [J].

Berrabah, Wahiba ;

Aumercier, Pierrette ;

Lefebvre, Philippe ;

Staels, Bart .

FEBS LETTERS, 2011, 585 (11) :1640-1650

[2] Retinoid signaling is attenuated by proteasome-mediated degradation of retinoid receptors in human keratinocyte HaCaT cells [J].

Boudjelal, M ;

Voorhees, JJ ;

Fisher, GJ .

EXPERIMENTAL CELL RESEARCH, 2002, 274 (01) :130-137

[3] Phosphorylation of the Retinoid X Receptor at the Omega loop, modulates the expression of retinoic-acid-target genes with a promoter context specificity [J].

Bruck, N ;

Bastien, J ;

Bour, G ;

Tarrade, A ;

Plassat, JL ;

Bauer, A ;

Adam-Stitah, S ;

Rochette-Egly, C .

CELLULAR SIGNALLING, 2005, 17 (10) :1229-1239

[4] Negative modulation of RXRα transcriptional activity by small ubiquitin-related modifier (SUMO) modification and its reversal by SUMO-specific protease SUSP1 [J].

Choi, Soo Joon ;

Chung, Sung Soo ;

Rho, Eun Jung ;

Lee, Hyung Woo ;

Lee, Moon Hee ;

Choi, Hueng-Sik ;

Seol, Jae Hong ;

Baek, Sung Hee ;

Bang, Ok Sun ;

Chung, Chin Ha .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (41) :30669-30677

[5] ApoE-Directed Therapeutics Rapidly Clear β-Amyloid and Reverse Deficits in AD Mouse Models [J].

Cramer, Paige E. ;

Cirrito, John R. ;

Wesson, Daniel W. ;

Lee, C. Y. Daniel ;

Karlo, J. Colleen ;

Zinn, Adriana E. ;

Casali, Brad T. ;

Restivo, Jessica L. ;

Goebel, Whitney D. ;

James, Michael J. ;

Brunden, Kurt R. ;

Wilson, Donald A. ;

Landreth, Gary E. .

SCIENCE, 2012, 335 (6075) :1503-1506

[6] PIASy-mediated sumoylation of Yin Yang 1 depends on their interaction but not the RING finger [J].

Deng, Zhiyong ;

Wan, Meimei ;

Sui, Guangchao .

MOLECULAR AND CELLULAR BIOLOGY, 2007, 27 (10) :3780-3792

[7] Small ubiquitin-like modifier (SUMO) modification of natively unfolded proteins tau and α-synuclein [J].

Dorval, V ;

Fraser, PE .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (15) :9919-9924

[8] Nuclear Receptors, RXR, and the Big Bang [J].

Evans, Ronald M. ;

Mangelsdorf, David J. .

CELL, 2014, 157 (01) :255-266

[9] The SUMO pathway: emerging mechanisms that shape specificity, conjugation and recognition [J].

Gareau, Jaclyn R. ;

Lima, Christopher D. .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2010, 11 (12) :861-871

[10] The optimal use of bexarotene in cutaneous T-cell lymphoma [J].

Gniadecki, R. ;

Assaf, C. ;

Bagot, M. ;

Dummer, R. ;

Duvic, M. ;

Knobler, R. ;

Ranki, A. ;

Schwandt, P. ;

Whittaker, S. .

BRITISH JOURNAL OF DERMATOLOGY, 2007, 157 (03) :433-440

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