HACE1, an E3 Ubiquitin Protein Ligase, Mitigates Kaposi's Sarcoma-Associated Herpesvirus Infection-Induced Oxidative Stress by Promoting Nrf2 Activity

Journal of Virology
Binod KumarBala Chandran

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV)-induced activation of nuclear factor erythroid 2-related factor 2 (Nrf2) is essential for both the expression of viral genes (latency) and modulation of the host antioxidant machinery. Reactive oxygen species (ROS) are also regulated by the ubiquitously expressed HACE1 protein (HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1), which targets the Rac1 protein for proteasomal degradation, and this blocks the generation of ROS by Rac1-dependent NADPH oxidases. In this study, we examined the role of HACE1 in KSHV infection. Elevated levels of HACE1 expression were observed in de novo KSHV-infected endothelial cells, KSHV latently infected TIVE-LTC and PEL cells, and Kaposi's sarcoma skin lesion cells. The increased HACE1 expression in the infected cells was mediated by KSHV latent protein kaposin A. HACE1 knockdown resulted in high Rac1 and Nox 1 (NADPH oxidase 1) activity, increased ROS (oxidative stress), increased cell death, and decreased KSHV gene expression. Loss of HACE1 impaired KSHV infection-induced phosphoinositide 3-kinase (PI3-K), protein kinase C-ζ (PKC-ζ), extracellular signal-regulated kinase 1/2 (ERK1/2), NF-κB, and Nrf2 activation and nuclear tr...Continue Reading

References

May 4, 1995·The New England Journal of Medicine·E CesarmanD M Knowles
Jan 1, 1996·Free Radical Biology & Medicine·K B Schwarz
Dec 10, 1996·Proceedings of the National Academy of Sciences of the United States of America·R Venugopal, A K Jaiswal
Apr 30, 1998·Current Opinion in Cell Biology·T Finkel
Feb 4, 2003·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·P NewsholmeR Curi
Jul 2, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Marcus S CookeJoseph Lunec
Apr 16, 2004·Heart·A M Shah, K M Channon
Nov 3, 2004·Trends in Molecular Medicine·Hozumi Motohashi, Masayuki Yamamoto
Dec 6, 2006·Drug Metabolism Reviews·Donna D Zhang
Jan 24, 2007·Physiological Reviews·Karen Bedard, Karl-Heinz Krause
Apr 5, 2007·Nature Protocols·Gustavo TiscorniaInder M Verma
Jul 27, 2007·Molecular Pharmacology·Sally E Purdom-DickinsonQin M Chen
Mar 6, 2008·Journal of Leukocyte Biology·Paola GasperiniGiovanna Tosato
Mar 11, 2010·Science Signaling·Gerasimos P Sykiotis, Dirk Bohmann
Jan 6, 2011·Proceedings of the National Academy of Sciences of the United States of America·Dongmei RenDonna D Zhang
Mar 3, 2011·Archives of Toxicology·Liam Baird, Albena T Dinkova-Kostova
Mar 4, 2011·Journal of Virology·Yuichi YagetaNobuyuki Hizawa
Oct 13, 2011·Nature Communications·Danming TangYanzhuang Wang
Jul 4, 2012·Antioxidants & Redox Signaling·Qi MaEnrique A Mesri
Jul 19, 2013·Nature Communications·Mads DaugaardPoul H Sorensen
Feb 12, 2014·Proceedings of the National Academy of Sciences of the United States of America·Barak RotblatPoul H Sorensen

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Citations

Apr 18, 2019·Current Opinion in HIV and AIDS·Nicole A Doria-Rose, Elise Landais
Apr 29, 2020·Expert Opinion on Therapeutic Targets·Thandeka MoyoPenny L Moore
Jul 25, 2019·Frontiers in Immunology·Katharina A MayerGuido A Gualdoni
Feb 20, 2021·Pharmacology & Therapeutics·Sunil SinghJ Sivaraman
Sep 29, 2020·Journal of Translational Internal Medicine·Hao QianYingxian Sun

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