IRTKS negatively regulates antiviral immunity through PCBP2 sumoylation-mediated MAVS degradation

Nature Communications
Pengyan XiaZusen Fan

Abstract

RNA virus infection is recognized by the RIG-I family of receptors that activate the mitochondrial adaptor MAVS, leading to the clearance of viruses. Antiviral signalling activation requires strict modulation to avoid damage to the host from exacerbated inflammation. Insulin receptor tyrosine kinase substrate (IRTKS) participates in actin bundling and insulin signalling and its deficiency causes insulin resistance. However, whether IRTKS is involved in the regulation of innate immunity remains elusive. Here we show that IRTKS deficiency causes enhanced innate immune responses against RNA viruses. IRTKS-mediated suppression of antiviral responses depends on the RIG-I-MAVS signalling pathway. IRTKS recruits the E2 ligase Ubc9 to sumoylate PCBP2 in the nucleus, which causes its cytoplasmic translocation during viral infection. The sumoylated PCBP2 associates with MAVS to initiate its degradation, leading to downregulation of antiviral responses. Thus, IRTKS functions as a negative modulator of excessive inflammation.

References

Jul 21, 2000·The Journal of Clinical Investigation·J E Pessin, A R Saltiel
Aug 10, 2000·Proceedings of the National Academy of Sciences of the United States of America·R M HuJ L Chen
May 11, 2002·RNA·Aleksandr V Makeyev, Stephen A Liebhaber
Mar 11, 2003·Proceedings of the National Academy of Sciences of the United States of America·Lauren D WoodScott W Hiebert
Aug 30, 2005·Nature Immunology·Taro KawaiShizuo Akira
Sep 13, 2005·Molecular Cell·Liang-Guo XuHong-Bing Shu
Apr 27, 2007·Proceedings of the National Academy of Sciences of the United States of America·Kei-ichiro ArimotoKunitada Shimotohno
Nov 9, 2007·Annual Review of Physiology·Akiko Taguchi, Morris F White
Jan 18, 2008·Nature·Chris B MooreJenny P-Y Ting
Apr 16, 2009·Proceedings of the National Academy of Sciences of the United States of America·Didier VingadassalomJohn M Leong
Jun 23, 2009·Seminars in Immunology·Peyman NakhaeiJohn Hiscott
Aug 20, 2009·Science Signaling·Kai YasukawaTakumi Koshiba
Sep 8, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yongxia JiaHui Zhong
Nov 3, 2009·Nature Immunology·Fuping YouZhengfan Jiang
Nov 17, 2009·Seminars in Cell & Developmental Biology·Sohail AhmedWenyu Bu
Nov 26, 2010·Proceedings of the National Academy of Sciences of the United States of America·Olli AitioPerttu Permi
Jan 18, 2011·International Reviews of Immunology·Himanshu KumarShizuo Akira
May 28, 2011·Immunity·Yueh-Ming Loo, Michael Gale
May 31, 2011·Cellular Signalling·Ingeborg HersJeremy M Tavaré
Aug 16, 2011·FEBS Letters·Gang ChenXin Zhang
Jan 10, 2012·Nature Reviews. Immunology·José M González-NavajasEyal Raz
Apr 10, 2012·Annual Review of Biochemistry·Jonathan S Bogan
Jun 12, 2013·Annual Review of Biochemistry·Annette Flotho, Frauke Melchior
Aug 27, 2013·The EMBO Journal·Pengyan XiaZusen Fan
Sep 11, 2013·Annual Review of Genetics·Stefan Jentsch, Ivan Psakhye
Oct 15, 2013·Journal of Molecular Biology·Jana L Jacobs, Carolyn B Coyne
Oct 26, 2013·Nature Protocols·F Ann RanFeng Zhang
Jan 7, 2014·Journal of Virology·Qian FengFrank J M van Kuppeveld
Jan 29, 2014·Nature Reviews. Endocrinology·Bart O Roep, Timothy I M Tree
Mar 25, 2014·Annual Review of Immunology·Jiaxi Wu, Zhijian J Chen

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Citations

Nov 18, 2015·The Journal of Experimental Medicine·Pengyan XiaZusen Fan
Feb 10, 2016·Current Opinion in Structural Biology·Jungsan Sohn, Sun Hur
Oct 4, 2016·Biochemical and Biophysical Research Communications·Lushen LiXi Zhan
Jun 8, 2017·Nature Communications·Pengyan XiaZusen Fan
Nov 23, 2018·European Journal of Immunology·Hongrui LiWeilin Chen
Oct 13, 2017·Open Biology·Yanfang YangShufang Liang
Dec 11, 2019·Nature Immunology·Andrea Ablasser, Sun Hur
May 2, 2017·Immune Network·Hyo Sun JinEun-Kyeong Jo
Dec 24, 2020·Trends in Cancer·Jessie S Kroonen, Alfred C O Vertegaal
Jul 11, 2021·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·Stephany Sánchez-OvandoPeter A B Wark

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Methods Mentioned

BETA
sumoylation
transfection
two-hybrid
pull-down
ubiquitination
ELISA
immunoprecipitation
confocal microscopy
flow cytometry
Gene knockout

Software Mentioned

GraphPad Prism
GPS

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