The E3 ubiquitin ligase Trim13 regulates Nur77 stability via casein kinase 2α

Scientific Reports
Bin HuangSuk-Hwan Baek

Abstract

Nur77 is a member of the NR4A subfamily of nuclear receptors and has been shown to regulate various biological processes such as apoptosis and inflammation. Here, we show that Nur77 ubiquitination is mediated by the tripartite motif 13 (Trim13), a RING-type E3 ubiquitin ligase. The interaction between Nur77 and Trim13 was confirmed by co-immunoprecipitation. Moreover, we found that Lys539 in Nur77 ubiquitination is targeted for Trim13, which leads to Nur77 degradation. The Trim13-mediated ubiquitination of Nur77 was optimal in the presence of the E2 enzyme UbcH5. Importantly, in addition to Trim13-mediated ubiquitination, the stability of Nur77 was also regulated by casein kinase 2α (CK2α). Pharmacological inhibition of CK2 markedly increased Nur77 levels, whereas overexpression of CK2α, but not its inactive mutant, dramatically decreased Nur77 levels by promoting Nur77 ubiquitination. CK2α phosphorylated Ser154 in Nur77 and thereby regulated Nur77 protein levels by promoting its ubiquitin-mediated degradation. Importantly, we also show that degradation of Nur77 is involved in TNFα-mediated IL-6 production via CK2α and Trim13. Taken together, these results suggest that the sequential phosphorylation and ubiquitination of Nur77 ...Continue Reading

References

Mar 29, 2001·Proceedings of the National Academy of Sciences of the United States of America·Y PekarskyC M Croce
Jul 5, 2001·The Journal of Biological Chemistry·N MasuyamaY Gotoh
Jun 26, 2002·The Journal of Biological Chemistry·K D Senali Abayratna WansaGeorge E O Muscat
Mar 13, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Flavio Meggio, Lorenzo A Pinna
Dec 3, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Lakita G CavinMarcello Arsura
Jan 25, 2005·Cardiovascular Research·José Martínez-González, Lina Badimon
Jun 21, 2005·The Journal of Biological Chemistry·Liming PeiPeter Tontonoz
Oct 15, 2005·The Biochemical Journal·Andrew D WingateJ Simon C Arthur
Nov 4, 2005·Angewandte Chemie·Christopher T WalshGregory J Gatto
Jul 29, 2006·Cell·Pier Paolo ScaglioniPier Paolo Pandolfi
Jul 29, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Peter I BontaCarlie J M de Vries
Feb 23, 2007·Molecular Biology of the Cell·Mikael LernerOlle Sangfelt
Aug 12, 2008·Nature Chemical Biology·Yanyan ZhanQiao Wu
Apr 13, 2010·Journal of Molecular and Cellular Cardiology·Qin ShaoBen He
Dec 28, 2010·Nature Neuroscience·Christophe AltierGerald W Zamponi
Feb 22, 2011·European Journal of Cell Biology·Hae Mi JooYoung Woo Jin
Mar 25, 2011·Biochemical Society Transactions·Jason P McMorrow, Evelyn P Murphy
Oct 8, 2011·Nature Reviews. Cancer·Shigetsugu Hatakeyama
Dec 24, 2011·Circulation Research·Anouk A J HamersCarlie J M de Vries
Jan 12, 2012·Biochemical and Biophysical Research Communications·Bjørn O Strøm, Ragnhild E Paulsen
Jul 14, 2012·Biochimica Et Biophysica Acta·Claudia M van TielCarlie J M de Vries
Sep 18, 2012·Nature Chemical Biology·Yan-yan ZhanQiao Wu
Dec 18, 2013·Journal of Molecular Biology·Ricardo RajsbaumGijs A Versteeg
Jul 1, 2014·Biochimica Et Biophysica Acta·Kondababu KurakulaCarlie J M de Vries
Apr 29, 2015·The Journal of Steroid Biochemistry and Molecular Biology·Stephen SafeRonald B Tjalkens
Jul 15, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kondababu KurakulaCarlie J M de Vries
Dec 5, 2015·Arteriosclerosis, Thrombosis, and Vascular Biology·Ping YangJianxin Sun
Oct 22, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·Yujie JiangLiao Pinhu
Jan 6, 2017·Expert Opinion on Therapeutic Targets·Ricardo Rodríguez-CalvoManuel Vázquez-Carrera
May 27, 2017·Proteins·Miguel Correa MarreroDick de Ridder
Jun 18, 2017·Cell Death and Differentiation·Long ZhangFangfang Zhou

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Citations

Mar 7, 2019·Bioscience Reports·Wei-Xian ChenYu-Lan Zhu
Oct 23, 2020·Proceedings of the National Academy of Sciences of the United States of America·Peng-Bo YangQiao Wu
Aug 13, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jonathan GagnonAndré Tremblay

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Methods Mentioned

BETA
ubiquitination
immunoprecipitation
transfection
PCR
transfections

Software Mentioned

GraphPad
AlphaEase
GraphPad Prism
MultiGauge
LAS
3000 Image Reader

Related Concepts

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