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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




Journal article



Publication Date





644 - 653


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