[HTML][HTML] Degradation of p27Kip cdk inhibitor triggered by Kaposi's sarcoma virus cyclin–cdk6 complex

M Ellis, YP Chew, L Fallis, S Freddersdorf… - The EMBO …, 1999 - embopress.org
M Ellis, YP Chew, L Fallis, S Freddersdorf, C Boshoff, RA Weiss, X Lu, S Mittnacht
The EMBO journal, 1999embopress.org
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 …
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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