Identification of Kaposi Sarcoma Herpesvirus (KSHV) vIRF1 Protein as a Novel Interaction Partner of Human Deubiquitinase USP7.

The Journal of Biological Chemistry
Sara ChavoshiVivian Saridakis

Abstract

Viral interferon regulatory factor 1 (vIRF1), a Kaposi sarcoma herpesvirus protein, destabilizes p53 by inhibiting p53 acetylation and Hdm2 phosphorylation. This leads to increased ubiquitination and degradation of p53 by Hdm2, which cripples the cellular p53-mediated antiviral response. Ubiquitin-specific protease 7 (USP7) deubiquitinates p53 and Hdm2 and regulates their stability. We identified an EGPS consensus sequence in vIRF1, which is identical to that found in Epstein-Barr virus nuclear antigen 1 (EBNA1) that interacts with the N-terminal domain of USP7 (USP7-NTD). GST pulldown assays demonstrated that vIRF1 interacts with USP7-NTD via its EGPS motif. NMR heteronuclear single quantum correlation (HSQC) analysis revealed chemical perturbations after titration of USP7-NTD with vIRF1 (44)SPGEGPSGTG(53) peptide. In contrast, these perturbations were reduced with a mutant vIRF1 peptide, (44)SPGEGPAGTG(53). Fluorescence polarization analysis indicated that the vIRF1 peptide interacted with USP7-NTD with a Kd of 2.0 μm. The crystal structure of the USP7-NTD·vIRF1 peptide complex revealed an identical mode of binding as that of the EBNA1 peptide to USP7-NTD. We also showed that USP7 interacts with vIRF1 in U2OS cells. Decreased...Continue Reading

References

May 22, 1998·Trends in Genetics : TIG·P S Moore, Y Chang
Nov 26, 1998·The Journal of Biological Chemistry·P F LambertJ N Brady
Nov 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·N H ChehabT D Halazonetis
Oct 12, 2000·Molecular and Cellular Biology·M LiJ U Jung
Jul 20, 2001·Journal of Virology·H NakamuraJ U Jung
Jul 12, 2003·The Journal of Biological Chemistry·Chris Boutell, Roger D Everett
Sep 25, 2003·The Journal of Biological Chemistry·Melissa N HolowatyLori Frappier
Apr 3, 2004·Nature·Jordan M CumminsBert Vogelstein
Jun 1, 2004·The Journal of Biological Chemistry·Jianhua FengBrian A Hemmings
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Sep 6, 2005·Virology Journal·Daniel C Edelman
Feb 14, 2006·Nature Structural & Molecular Biology·Yi ShengLori Frappier
Oct 12, 2007·Nature Reviews. Molecular Cell Biology·Rosa Bernardi, Pier Paolo Pandolfi
Nov 17, 2007·Nature Protocols·Axel T Brunger
Dec 19, 2007·Advances in Pharmacology·Peter C AngelettiCharles Wood
Apr 24, 2010·Future Virology·John A West, Blossom Damania
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Clemens VonrheinGérard Bricogne
Nov 8, 2011·Nature Structural & Molecular Biology·Hye-Ra LeeJae U Jung
Jan 1, 2011·Frontiers in Immunology·Sarah R Jacobs, Blossom Damania
Apr 23, 2013·The Journal of Biological Chemistry·Feroz SarkariYi Sheng
Jan 21, 2014·Infectious Agents and Cancer·Kenneth AlibekBolat Sultankulov

❮ Previous
Next ❯

Citations

Jun 4, 2016·International Journal of Molecular Sciences·Enea Gino Di DomenicoFabrizio Ensoli
Sep 7, 2016·Mediators of Inflammation·Gloria Lopez-Castejon, Mariola J Edelmann
May 22, 2018·Cell Biochemistry and Function·Farjana Yeasmin KhusbuHan-Chun Chen
Oct 11, 2019·Journal of Virology·Santiago VidalCarmen Rivas
Apr 30, 2017·Biological Chemistry·Sandra Koch, Thomas F Schulz
Oct 28, 2018·Scientific Reports·Anna GeorgesLori Frappier
May 18, 2018·Nature Reviews. Microbiology·Yi-Chieh Perng, Deborah J Lenschow
Jul 4, 2018·Signal Transduction and Targeted Therapy·Seemana BhattacharyaMrinal K Ghosh
Feb 26, 2019·Scientific Reports·Anna GeorgesLori Frappier
Aug 10, 2019·Journal of Oncology·Yueshuo LiYa Cao
May 23, 2019·Frontiers in Pharmacology·Zhiru WangYichao Zheng
Jan 28, 2021·International Journal of Molecular Sciences·Ying Li, David Reverter
Jul 1, 2020·Virus Research·Anna Bojagora, Vivian Saridakis
Nov 7, 2020·Drug Discovery Today·Lauraine NininahazweZhe-Sheng Chen
Nov 16, 2021·EMBO Reports·Sunali MehtaAntony W Braithwaite

❮ Previous
Next ❯

Related Concepts

Related Feeds

Ataxia telangiectasia (MDS)

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.