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Blood, 15 January 2006, Vol. 107, No. 2, pp. 725-732. Prepublished online as a Blood First Edition Paper on September 13, 2005; DOI 10.1182/blood-2005-06-2534. This Article Full Text (PDF) All Versions of this Article: 2005-06-2534v1 107/2/725    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sarek, G. Articles by Ojala, P. Search for Related Content PubMed PubMed Citation Articles by Sarek, G. Articles by Ojala, P. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 27, 2005 Accepted September 1, 2005 KSHV viral cyclin inactivates p27KIP1 through Ser10 and Thr187 phosphorylation in proliferating primary effusion lymphomas Grzegorz Sarek, Annika Jarviluoma, and Paivi Ojala* Molecular Cancer Biology Program, Institute of Biomedicine, Biomedicum Helsinki, Helsinki, Finland * Corresponding author; email: Paivi.Ojala{at}helsinki.fi. Kaposi's sarcoma herpesvirus infection is consistently associated with primary effusion lymphomas (PELs) that are non-Hodgkin's lymphomas of B-cell origin. All PEL cells are latently infected with KSHV and express latent viral proteins such as the viral cyclin (v-cyclin), which has previously been implicated in downregulation of the cell cycle inhibitor p27KIP1 levels via phosphorylation on Thr187. PEL cells retain high levels of p27KIP1 but yet proliferate actively, which has left the biological significance of this p27KIP1 destabilization somewhat elusive. We have recently demonstrated that v-cyclin and p27KIP1 stably associate in PEL cells. Here we demonstrate that v-cyclin together with its kinase partner CDK6 phosphorylates the associated p27KIP1 in PEL cells which represent a biologically relevant model system for KSHV pathobiology. During latent viral replication p27KIP1 was phosphorylated by v-cyclin-CDK6 predominantly on Ser10 which enhances its cytoplasmic localization. Interestingly, upon reactivation of KSHV lytic cycle v-cyclin-CDK6 phosphorylated p27KIP1 on Thr187, which resulted in downregulation of p27KIP1 protein levels. These findings indicate that v-cyclin modulates the cell cycle inhibitory function of p27KIP1 by phosphorylation in PELs, and also suggest a novel role for v-cyclin in the lytic reactivation of KSHV. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Carbone, E. Cesarman, M. Spina, A. Gloghini, and T. F. Schulz HIV-associated lymphomas and gamma-herpesviruses Blood, February 5, 2009; 113(6): 1213 - 1224. [Abstract] [Full Text] [PDF] P.-C. Chang and M. Li Kaposi's Sarcoma-Associated Herpesvirus K-Cyclin Interacts with Cdk9 and Stimulates Cdk9-Mediated Phosphorylation of p53 Tumor Suppressor J. Virol., January 1, 2008; 82(1): 278 - 290. [Abstract] [Full Text] [PDF] M-Q Du, C M Bacon, and P G Isaacson Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 and lymphoproliferative disorders J. Clin. Pathol., December 1, 2007; 60(12): 1350 - 1357. [Abstract] [Full Text] [PDF] C. Munoz-Fontela, M. A. Garcia, M. Collado, L. Marcos-Villar, P. Gallego, M. Esteban, and C. Rivas Control of virus infection by tumour suppressors Carcinogenesis, June 1, 2007; 28(6): 1140 - 1144. [Abstract] [Full Text] [PDF] A. Jarviluoma, E. S. Child, G. Sarek, P. Sirimongkolkasem, G. Peters, P. M. Ojala, and D. J. Mann Phosphorylation of the Cyclin-Dependent Kinase Inhibitor p21Cip1 on Serine 130 Is Essential for Viral Cyclin-Mediated Bypass of a p21Cip1-Imposed G1 Arrest. Mol. Cell. Biol., March 1, 2006; 26(6): 2430 - 2440. [Abstract] [Full Text] [PDF]

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