NF-kappaB suppression by the deubiquitinating enzyme Cezanne: a novel negative feedback loop in pro-inflammatory signaling

The Journal of Biological Chemistry
Karine EnesaPaul C Evans

Abstract

Transcription factors belonging to the NF-kappaB family regulate inflammation by inducing pro-inflammatory molecules (e.g. interleukin (IL)-8) in response to cytokines (e.g. tumor necrosis factor (TNF) alpha, IL-1) or other stimuli. Several negative regulators of NF-kappaB, including the ubiquitin-editing enzyme A20, participate in the resolution of inflammatory responses. We report that Cezanne, a member of the A20 family of the deubiquitinating cysteine proteases, can be induced by TNFalpha in cultured cells. Silencing of endogenous Cezanne using small interfering RNA led to elevated NF-kappaB luciferase reporter gene activity and enhanced expression of IL-8 transcripts in TNFalpha-treated cells. Thus we conclude that endogenous Cezanne can attenuate NF-kappaB activation and the induction of pro-inflammatory transcripts in response to TNF receptor (TNFR) signaling. Overexpression studies revealed that Cezanne suppressed NF-kappaB nuclear translocation and transcriptional activity by targeting the TNFR signaling pathway at the level of the IkappaB kinase complex or upstream from it. These effects were not observed in a form of Cezanne that was mutated at the catalytic cysteine residue (Cys209), indicating that the deubiquitina...Continue Reading

References

Jun 25, 1996·Proceedings of the National Academy of Sciences of the United States of America·H Y SongD V Goeddel
Jun 3, 2000·Nature Genetics·G R BignellS Rasmussen
Jul 19, 2001·Nature·C WangZ J Chen
Jul 21, 2001·The Biochemical Journal·P C EvansP J Kilshaw
Apr 19, 2003·The Journal of Biological Chemistry·Paul C EvansPeter J Kilshaw
Dec 9, 2003·Nature Immunology·Luis SoaresC Garrison Fathman
Feb 26, 2004·Proceedings of the National Academy of Sciences of the United States of America·Anthony G PasseriniPeter F Davies
Mar 24, 2004·The Journal of Cell Biology·Yanzhuang WangYangzhuang Wang
Jun 16, 2004·Current Opinion in Cell Biology·Lijun Sun, Zhijian J Chen
Aug 26, 2004·Molecular Cell·Atsuhiro KanayamaZhijian J Chen
Sep 17, 2004·Genes & Development·Matthew S Hayden, Sankar Ghosh
Nov 30, 2004·Laboratory Investigation; a Journal of Technical Methods and Pathology·Kristopher S Cunningham, Avrum I Gotlieb
Dec 2, 2004·Biochimica Et Biophysica Acta·Alexander Y Amerik, Mark Hochstrasser
Jun 15, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jason PartridgePaul C Evans

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Citations

Feb 7, 2012·Cellular & Molecular Immunology·Wenzhuo Y WangJian-Dong Li
Dec 2, 2010·Cell Research·Edward W Harhaj, Vishva M Dixit
Jul 21, 2011·Nature Immunology·Jürgen Ruland
Jun 7, 2008·Nature Reviews. Immunology·Shao-Cong Sun
Jul 25, 2009·Nature Reviews. Molecular Cell Biology·David KomanderSylvie Urbé
Sep 9, 2010·Nature Reviews. Molecular Cell Biology·Peter VandenabeeleGuido Kroemer
May 5, 2011·Nature Structural & Molecular Biology·Christian Behrends, J Wade Harper
Oct 15, 2011·Oncogene·J M FraileC López-Otín
Nov 26, 2010·The Journal of Biological Chemistry·R Sean McNallyJenny P-Y Ting
Feb 11, 2009·Antioxidants & Redox Signaling·Geoffrey Gloire, Jacques Piette
Jul 21, 2009·Cardiovascular Research·Pasquale FasanaroFabio Martelli
Mar 20, 2010·Cold Spring Harbor Perspectives in Biology·Ingrid E Wertz, Vishva M Dixit
Mar 24, 2009·Annual Review of Immunology·Sivakumar Vallabhapurapu, Michael Karin
Jul 21, 2011·BMC Systems Biology·Pernille YdeAla Trusina
Apr 13, 2011·PloS One·Apostolos ZaravinosDemetrios A Spandidos
Mar 29, 2014·PLoS Pathogens·Ben A Bailey-ElkinBrian L Mark
Jun 10, 2011·F1000 Medicine Reports·Christina M WarboysPaul C Evans
Oct 2, 2013·Annual Review of Physiology·Dana E ChristoffersonJunying Yuan
Feb 7, 2014·Molecular Biology of the Cell·Fen GuoAndrew Leask
Mar 4, 2010·Cellular and Molecular Life Sciences : CMLS·Franky Van HerreweghePeter Vandenabeele
Aug 15, 2014·BioMed Research International·Seemana Bhattacharya, Mrinal Kanti Ghosh
Sep 27, 2012·BMB Reports·Eun-Woo LeeJaewhan Song
Apr 14, 2016·Cellular and Molecular Life Sciences : CMLS·Yves DondelingerHenning Walczak
Feb 24, 2010·Clinical Science·Kim Van der HeidenPaul C Evans
Sep 6, 2011·The Biochemical Journal·Iraia García-SantistebanJose A Rodríguez
Feb 2, 2015·Journal of Translational Medicine·Jia-hong WangRong-ping Guo
Dec 7, 2011·Small GTPases·Michelle de la VegaJames A Johnston
Feb 13, 2013·Proceedings of the National Academy of Sciences of the United States of America·Puck B van KasterenMarjolein Kikkert
Jun 7, 2011·Trends in Biochemical Sciences·Anja Bremm, David Komander
Jun 3, 2008·Cytokine & Growth Factor Reviews·Ingrid E Wertz, Vishva M Dixit
Sep 7, 2016·Mediators of Inflammation·Gloria Lopez-Castejon, Mariola J Edelmann
Oct 20, 2009·Cell Host & Microbe·Dominique ThevenonMarie-Odile Fauvarque
Feb 17, 2009·Trends in Cell Biology·Meike Broemer, Pascal Meier

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