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

ABSTRACT: 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 ? 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 ? 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.

SUBMITTER: Kofod-Olsen E

PROVIDER: S-EPMC3608612 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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

Kofod-Olsen Emil E Møller Janni M L JM Schleimann Mariane H MH Bundgaard Bettina B Bak Rasmus O RO Øster Bodil B Mikkelsen Jacob G JG Hupp Ted T Höllsberg Per P

PloS one 20130326 3

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 con ...[more]

PMID: 23555634

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Dataset Information

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

Publications

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

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