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. 1999 Feb 1;18(3):644-53.
doi: 10.1093/emboj/18.3.644.

Degradation of p27(Kip) cdk inhibitor triggered by Kaposi's sarcoma virus cyclin-cdk6 complex

M Ellis  1 , Y P Chew, L Fallis, S Freddersdorf, C Boshoff, R A Weiss, X Lu, S Mittnacht
Affiliations

Degradation of p27(Kip) cdk inhibitor triggered by Kaposi's sarcoma virus cyclin-cdk6 complex

M Ellis et al. EMBO J. .

Abstract

The Kaposi's sarcoma-associated human herpesvirus 8 (KSHV/HHV8) encodes a protein similar to cellular cyclins. This cyclin is most closely related to cellular D-type cyclins, but biochemically it behaves atypically in various respects. Complexes formed between the viral cyclin and the cyclin-dependent kinase subunit, cdk6, can phosphorylate a wider range of substrates and are resistant to cdk inhibitory proteins. We show here that the KSHV-cyclin-cdk6 complex phosphorylates p27(Kip) on a C-terminal threonine that is implicated in destabilization of this cdk inhibitor. Expression of the viral cyclin in tissue culture cells overcomes a cell cycle block by p27(Kip). However, full cell-cycle transit of these cells appears to depend on C-terminal phosphorylation of p27(Kip) and seems to involve transactivation of other cellular cyclin-dependent kinases. A p27(Kip)-phosphorylating cdk6 complex exists in cell lines derived from primary effusion lymphoma and in Kaposi's sarcoma, this indicating that virally induced p27(Kip) degradation may occur in KSHV-associated tumours.

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References

    1. Cell. 1991 Sep 20;66(6):1071-4 - PubMed
    1. Methods Enzymol. 1991;201:110-49 - PubMed
    1. EMBO J. 1995 Oct 2;14(19):4814-26 - PubMed
    1. Genes Dev. 1995 Aug 1;9(15):1831-45 - PubMed
    1. Blood. 1995 Sep 1;86(5):1924-30 - PubMed

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