Merkel cell polyomavirus small T antigen targets the NEMO adaptor protein to disrupt inflammatory signaling

Journal of Virology
David A GriffithsAdrian Whitehouse

Abstract

Merkel cell carcinoma (MCC) is a highly aggressive nonmelanoma skin cancer arising from epidermal mechanoreceptor Merkel cells. In 2008, a novel human polyomavirus, Merkel cell polyomavirus (MCPyV), was identified and is strongly implicated in MCC pathogenesis. Currently, little is known regarding the virus-host cell interactions which support virus replication and virus-induced mechanisms in cellular transformation and metastasis. Here we identify a new function of MCPyV small T antigen (ST) as an inhibitor of NF-κB-mediated transcription. This effect is due to an interaction between MCPyV ST and the NF-κB essential modulator (NEMO) adaptor protein. MCPyV ST expression inhibits IκB kinase α (IKKα)/IKKβ-mediated IκB phosphorylation, which limits translocation of the NF-κB heterodimer to the nucleus. Regulation of this process involves a previously undescribed interaction between MCPyV ST and the cellular phosphatase subunits, protein phosphatase 4C (PP4C) and/or protein phosphatase 2A (PP2A) Aβ, but not PP2A Aα. Together, these results highlight a novel function of MCPyV ST to subvert the innate immune response, allowing establishment of early or persistent infection within the host cell.

References

Apr 1, 1991·Molecular and Cellular Biology·S I YangM C Mumby
Nov 13, 1999·Journal of Virology·Kersten T HallAdrian Whitehouse
Dec 28, 1999·Transplantation·I Penn, M R First
Jun 3, 2000·Annual Review of Immunology·M Karin, Y Ben-Neriah
Mar 30, 2001·The Journal of Biological Chemistry·Delyth J Goodwin, Adrian Whitehouse
Feb 21, 2002·Lancet·Eric A EngelsRobert W Miller
May 3, 2002·The Journal of Biological Chemistry·Dimitry SpitkovskyM Lienhard Schmitz
Oct 22, 2002·Journal of Virology·Kersten T HallAdrian Whitehouse
Aug 2, 2003·Journal of Cell Science·Nigel FieldMary Collins
Oct 25, 2003·Journal of the American Academy of Dermatology·Maria Agelli, Limin X Clegg
Feb 14, 2004·Journal of Virology·Christelle Camus-BouclainvilleFrédérique Messud-Petit
Sep 2, 2004·Journal of Cell Science·Stefanie JägerEeva-Liisa Eskelinen
Sep 17, 2004·Genes & Development·Matthew S Hayden, Sankar Ghosh
Nov 22, 2005·Oncogene·Jason D Arroyo, William C Hahn
Oct 31, 2006·Oncogene·T D Gilmore, M Herscovitch
May 8, 2007·Cellular and Molecular Life Sciences : CMLS·U MoensM Johannessen
Jan 19, 2008·Science·Huichen FengPatrick S Moore
Jan 25, 2008·Cancer Metastasis Reviews·Anna A Sablina, William C Hahn
Mar 26, 2008·Nature Immunology·Hui-Yan LiXue-Min Zhang
Apr 22, 2008·Methods in Molecular Biology·Vojo Deretic
May 2, 2008·International Journal of Cancer. Journal International Du Cancer·Harald Zur Hausen
Sep 25, 2008·Proceedings of the National Academy of Sciences of the United States of America·Masahiro ShudaYuan Chang
Oct 22, 2008·The Journal of Cell Biology·Laura Trinkle-MulcahyAngus Lamond
Nov 22, 2008·Cellular and Molecular Life Sciences : CMLS·Jürgen C BeckerRoland Houben
Jun 10, 2009·Seminars in Cancer Biology·Jingwei ChengBrian S Schaffhausen
Nov 27, 2010·Molecules and Cells·Dong-Joo YouJong-Ik Hwang
Jan 25, 2011·Microbes and Infection·Kathryn H Richards, Andrew Macdonald
Aug 16, 2011·The Journal of Clinical Investigation·Masahiro ShudaPatrick S Moore
Nov 5, 2011·Cellular Microbiology·Gaëlle Le Negrate
Jan 21, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Valentina NardiDora Dias-Santagata
Feb 4, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Crystal M H RandallJoanna L Shisler
May 11, 2012·Science Translational Medicine·Reety AroraPatrick S Moore
Aug 31, 2013·Nature Reviews. Molecular Cell Biology·Kristopher ClarkPhilip Cohen

Citations

May 27, 2015·Viruses·Robert Hollingworth, Roger J Grand
Dec 31, 2015·Head & Neck·Brett A MilesEducation Committee of the American Head and Neck Society (AHNS)
Dec 1, 2017·Journal of Clinical Medicine·Uyen Ngoc MuiStephen K Tyring
Feb 21, 2018·The Journal of Biological Chemistry·Gabrielė StakaitytėAdrian Whitehouse
Nov 3, 2017·Journal of Virology·Gabrielė StakaitytėAdrian Whitehouse
Dec 15, 2017·Virology : Research and Treatment·Camila Freze BaezSerena Delbue
Aug 8, 2018·Viruses·Liyao DengXiaoyue Chen
Aug 12, 2016·Journal of Virology·Jennifer J WoodDavid J Hughes
Jan 30, 2015·Journal of Virology·Hyun Jin KwunPatrick S Moore
Oct 14, 2017·PLoS Pathogens·Jingwei ChengJames A DeCaprio
Sep 13, 2017·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Sharon E Hopcraft, Blossom Damania
Jan 28, 2014·Current Opinion in Otolaryngology & Head and Neck Surgery·Gerhard F Huber
Jun 11, 2019·International Journal of Cancer. Journal International Du Cancer·Satendra KumarWeng-Onn Lui
Aug 25, 2018·Oncotarget·Kashif RasheedU Moens
Oct 10, 2015·Oncotarget·Adrian Whitehouse, Andrew Macdonald
Jul 9, 2020·The Biochemical Journal·Samuel J DobsonAdrian Whitehouse
Mar 18, 2020·Frontiers in Cell and Developmental Biology·Tiziana VescovoManuela Antonioli
Dec 1, 2017·Cancer Immunology, Immunotherapy : CII·Jürgen C BeckerDavid Schrama
Oct 6, 2018·Nature Reviews. Clinical Oncology·Paul W HarmsInternational Workshop on Merkel Cell Carcinoma Research (IWMCC) Working Group
Aug 15, 2019·International Journal of Molecular Sciences·U Moens, Andrew Macdonald
Apr 19, 2015·Cell Communication and Signaling : CCS·Ichiro MurakamiTadashi Yoshino
Aug 24, 2018·Cell Communication and Signaling : CCS·Ichiro MurakamiFrancis Jaubert
Jul 9, 2020·Cancers·Valeria PietropaoloU Moens
Aug 6, 2020·Molecular Cancer Research : MCR·Jiawei ZhaoRichard C Wang

Related Concepts

IKBKG protein, human
Antigens, Neoplasm, Viral
Resistance, Natural
Phosphorylation
Plasma Protein Binding Capacity
Papilloma, Shope
Merkel Cell Carcinoma
Ig-EBP-1
Polyomavirus Infections
IkappaB Kinase beta

Related Feeds

BK Virus Infection

BK virus infection is a significant complication of modern immunosuppression used in kidney transplantation. Discover the latest research on BK virus infection here.