Nucleophosmin phosphorylation by v-cyclin-CDK6 controls KSHV latency.

Nucleophosmin (NPM) is a multifunctional nuclear phosphoprotein and a histone chaperone implicated in chromatin organization and transcription control. Oncogenic Kaposi's sarcoma herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma, primary effusion lymphoma (PEL) and multicentr...

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Autores principales:	Grzegorz Sarek, Annika Järviluoma, Henna M Moore, Sari Tojkander, Salla Vartia, Peter Biberfeld, Marikki Laiho, Päivi M Ojala
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/fde858a70594489799a0ec0cfa14078d
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spelling	oai:doaj.org-article:fde858a70594489799a0ec0cfa14078d2021-11-25T05:48:13ZNucleophosmin phosphorylation by v-cyclin-CDK6 controls KSHV latency.1553-73661553-737410.1371/journal.ppat.1000818https://doaj.org/article/fde858a70594489799a0ec0cfa14078d2010-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20333249/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Nucleophosmin (NPM) is a multifunctional nuclear phosphoprotein and a histone chaperone implicated in chromatin organization and transcription control. Oncogenic Kaposi's sarcoma herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma, primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). In the infected host cell KSHV displays two modes of infection, the latency and productive viral replication phases, involving extensive viral DNA replication and gene expression. A sustained balance between latency and reactivation to the productive infection state is essential for viral persistence and KSHV pathogenesis. Our study demonstrates that the KSHV v-cyclin and cellular CDK6 kinase phosphorylate NPM on threonine 199 (Thr199) in de novo and naturally KSHV-infected cells and that NPM is phosphorylated to the same site in primary KS tumors. Furthermore, v-cyclin-mediated phosphorylation of NPM engages the interaction between NPM and the latency-associated nuclear antigen LANA, a KSHV-encoded repressor of viral lytic replication. Strikingly, depletion of NPM in PEL cells leads to viral reactivation, and production of new infectious virus particles. Moreover, the phosphorylation of NPM negatively correlates with the level of spontaneous viral reactivation in PEL cells. This work demonstrates that NPM is a critical regulator of KSHV latency via functional interactions with v-cyclin and LANA.Grzegorz SarekAnnika JärviluomaHenna M MooreSari TojkanderSalla VartiaPeter BiberfeldMarikki LaihoPäivi M OjalaPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 6, Iss 3, p e1000818 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Grzegorz Sarek Annika Järviluoma Henna M Moore Sari Tojkander Salla Vartia Peter Biberfeld Marikki Laiho Päivi M Ojala Nucleophosmin phosphorylation by v-cyclin-CDK6 controls KSHV latency.
description	Nucleophosmin (NPM) is a multifunctional nuclear phosphoprotein and a histone chaperone implicated in chromatin organization and transcription control. Oncogenic Kaposi's sarcoma herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma, primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). In the infected host cell KSHV displays two modes of infection, the latency and productive viral replication phases, involving extensive viral DNA replication and gene expression. A sustained balance between latency and reactivation to the productive infection state is essential for viral persistence and KSHV pathogenesis. Our study demonstrates that the KSHV v-cyclin and cellular CDK6 kinase phosphorylate NPM on threonine 199 (Thr199) in de novo and naturally KSHV-infected cells and that NPM is phosphorylated to the same site in primary KS tumors. Furthermore, v-cyclin-mediated phosphorylation of NPM engages the interaction between NPM and the latency-associated nuclear antigen LANA, a KSHV-encoded repressor of viral lytic replication. Strikingly, depletion of NPM in PEL cells leads to viral reactivation, and production of new infectious virus particles. Moreover, the phosphorylation of NPM negatively correlates with the level of spontaneous viral reactivation in PEL cells. This work demonstrates that NPM is a critical regulator of KSHV latency via functional interactions with v-cyclin and LANA.
format	article
author	Grzegorz Sarek Annika Järviluoma Henna M Moore Sari Tojkander Salla Vartia Peter Biberfeld Marikki Laiho Päivi M Ojala
author_facet	Grzegorz Sarek Annika Järviluoma Henna M Moore Sari Tojkander Salla Vartia Peter Biberfeld Marikki Laiho Päivi M Ojala
author_sort	Grzegorz Sarek
title	Nucleophosmin phosphorylation by v-cyclin-CDK6 controls KSHV latency.
title_short	Nucleophosmin phosphorylation by v-cyclin-CDK6 controls KSHV latency.
title_full	Nucleophosmin phosphorylation by v-cyclin-CDK6 controls KSHV latency.
title_fullStr	Nucleophosmin phosphorylation by v-cyclin-CDK6 controls KSHV latency.
title_full_unstemmed	Nucleophosmin phosphorylation by v-cyclin-CDK6 controls KSHV latency.
title_sort	nucleophosmin phosphorylation by v-cyclin-cdk6 controls kshv latency.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/fde858a70594489799a0ec0cfa14078d
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Nucleophosmin phosphorylation by v-cyclin-CDK6 controls KSHV latency.

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