Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1093/emboj/18.3.644

Type

Journal article

Journal

EMBO J

Publication Date

01/02/1999

Volume

18

Pages

644 - 653

Keywords

Base Sequence, Binding Sites, CDC2-CDC28 Kinases, Cell Cycle, Cell Cycle Proteins, Cyclin-Dependent Kinase 2, Cyclin-Dependent Kinase 6, Cyclin-Dependent Kinase Inhibitor p27, Cyclin-Dependent Kinases, Cyclins, DNA Primers, Enzyme Inhibitors, Herpesvirus 8, Human, Humans, Microtubule-Associated Proteins, Phosphorylation, Protein-Serine-Threonine Kinases, Sarcoma, Kaposi, Tumor Cells, Cultured, Tumor Suppressor Proteins