Viral cyclin-cyclin-dependent kinase 6 complexes initiate nuclear DNA replication.
AffiliationGene Regulation Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom.
MetadataShow full item record
AbstractThe cyclins encoded by Kaposi sarcoma-associated herpesvirus and herpesvirus saimiri are homologs of human D-type cyclins. However, when complexed to cdk6, they have several activities that distinguish them from D-type cyclin-cdk6 complexes, including resistance to cyclin-dependent kinase inhibitors and an enhanced substrate range. We find that viral cyclins interact with and phosphorylate proteins involved in replication initiation. Using mammalian in vitro replication systems, we show that viral cyclin-cdk6 complexes can directly trigger the initiation of DNA synthesis in isolated late-G(1)-phase nuclei. Viral cyclin-cdk6 complexes share this capacity with cyclin A-cdk2, demonstrating that in addition to functioning as G(1)-phase cyclin-cdk complexes, they function as S-phase cyclin-cdk complexes.
CitationViral cyclin-cyclin-dependent kinase 6 complexes initiate nuclear DNA replication. 2001, 21 (2):624-35 Mol. Cell. Biol.
JournalMolecular and Cellular Biology
- Herpes viral cyclin/Cdk6 complexes evade inhibition by CDK inhibitor proteins.
- Authors: Swanton C, Mann DJ, Fleckenstein B, Neipel F, Peters G, Jones N
- Issue date: 1997 Nov 13
- Constitutively active K-cyclin/cdk6 kinase in Kaposi sarcoma-associated herpesvirus-infected cells.
- Authors: Van Dross R, Yao S, Asad S, Westlake G, Mays DJ, Barquero L, Duell S, Pietenpol JA, Browning PJ
- Issue date: 2005 May 4
- Differential phosphorylation of T-47D human breast cancer cell substrates by D1-, D3-, E-, and A-type cyclin-CDK complexes.
- Authors: Sarcevic B, Lilischkis R, Sutherland RL
- Issue date: 1997 Dec 26
- Differential regulation of retinoblastoma tumor suppressor protein by G(1) cyclin-dependent kinase complexes in vivo.
- Authors: Ezhevsky SA, Ho A, Becker-Hapak M, Davis PK, Dowdy SF
- Issue date: 2001 Jul
- Degradation of p27(Kip) cdk inhibitor triggered by Kaposi's sarcoma virus cyclin-cdk6 complex.
- Authors: Ellis M, Chew YP, Fallis L, Freddersdorf S, Boshoff C, Weiss RA, Lu X, Mittnacht S
- Issue date: 1999 Feb 1