Inhibition of p53-dependent, but not p53-independent, cell death by U19 protein from human herpesvirus 6B.

Infection with human herpesvirus (HHV)-6B alters cell cycle progression and stabilizes tumor suppressor protein p53. In this study, we have analyzed the activity of p53 after stimulation with p53-dependent and -independent DNA damaging agents during HHV-6B infection. Microarray analysis, Western blo...

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Autores principales: Emil Kofod-Olsen, Janni M L Møller, Mariane H Schleimann, Bettina Bundgaard, Rasmus O Bak, Bodil Øster, Jacob G Mikkelsen, Ted Hupp, Per Höllsberg
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:47cab761a6914845b4a9830b3b2071cd2021-11-18T07:52:03ZInhibition of p53-dependent, but not p53-independent, cell death by U19 protein from human herpesvirus 6B.1932-620310.1371/journal.pone.0059223https://doaj.org/article/47cab761a6914845b4a9830b3b2071cd2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23555634/?tool=EBIhttps://doaj.org/toc/1932-6203Infection with human herpesvirus (HHV)-6B alters cell cycle progression and stabilizes tumor suppressor protein p53. In this study, we have analyzed the activity of p53 after stimulation with p53-dependent and -independent DNA damaging agents during HHV-6B infection. Microarray analysis, Western blotting and confocal microscopy demonstrated that HHV-6B-infected cells were resistant to p53-dependent arrest and cell death after γ irradiation in both permissive and non-permissive cell lines. In contrast, HHV-6B-infected cells died normally through p53-independet DNA damage induced by UV radiation. Moreover, we identified a viral protein involved in inhibition of p53 during HHV-6B-infection. The protein product from the U19 ORF was able to inhibit p53-dependent signaling following γ irradiation in a manner similar to that observed during infection. Similar to HHV-6B infection, overexpression of U19 failed to rescue the cells from p53-independent death induced by UV radiation. Hence, infection with HHV-6B specifically blocks DNA damage-induced cell death associated with p53 without inhibiting the p53-independent cell death response. This block in p53 function can in part be ascribed to the activities of the viral U19 protein.Emil Kofod-OlsenJanni M L MøllerMariane H SchleimannBettina BundgaardRasmus O BakBodil ØsterJacob G MikkelsenTed HuppPer HöllsbergPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e59223 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Emil Kofod-Olsen
Janni M L Møller
Mariane H Schleimann
Bettina Bundgaard
Rasmus O Bak
Bodil Øster
Jacob G Mikkelsen
Ted Hupp
Per Höllsberg
Inhibition of p53-dependent, but not p53-independent, cell death by U19 protein from human herpesvirus 6B.
description Infection with human herpesvirus (HHV)-6B alters cell cycle progression and stabilizes tumor suppressor protein p53. In this study, we have analyzed the activity of p53 after stimulation with p53-dependent and -independent DNA damaging agents during HHV-6B infection. Microarray analysis, Western blotting and confocal microscopy demonstrated that HHV-6B-infected cells were resistant to p53-dependent arrest and cell death after γ irradiation in both permissive and non-permissive cell lines. In contrast, HHV-6B-infected cells died normally through p53-independet DNA damage induced by UV radiation. Moreover, we identified a viral protein involved in inhibition of p53 during HHV-6B-infection. The protein product from the U19 ORF was able to inhibit p53-dependent signaling following γ irradiation in a manner similar to that observed during infection. Similar to HHV-6B infection, overexpression of U19 failed to rescue the cells from p53-independent death induced by UV radiation. Hence, infection with HHV-6B specifically blocks DNA damage-induced cell death associated with p53 without inhibiting the p53-independent cell death response. This block in p53 function can in part be ascribed to the activities of the viral U19 protein.
format article
author Emil Kofod-Olsen
Janni M L Møller
Mariane H Schleimann
Bettina Bundgaard
Rasmus O Bak
Bodil Øster
Jacob G Mikkelsen
Ted Hupp
Per Höllsberg
author_facet Emil Kofod-Olsen
Janni M L Møller
Mariane H Schleimann
Bettina Bundgaard
Rasmus O Bak
Bodil Øster
Jacob G Mikkelsen
Ted Hupp
Per Höllsberg
author_sort Emil Kofod-Olsen
title Inhibition of p53-dependent, but not p53-independent, cell death by U19 protein from human herpesvirus 6B.
title_short Inhibition of p53-dependent, but not p53-independent, cell death by U19 protein from human herpesvirus 6B.
title_full Inhibition of p53-dependent, but not p53-independent, cell death by U19 protein from human herpesvirus 6B.
title_fullStr Inhibition of p53-dependent, but not p53-independent, cell death by U19 protein from human herpesvirus 6B.
title_full_unstemmed Inhibition of p53-dependent, but not p53-independent, cell death by U19 protein from human herpesvirus 6B.
title_sort inhibition of p53-dependent, but not p53-independent, cell death by u19 protein from human herpesvirus 6b.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/47cab761a6914845b4a9830b3b2071cd
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