The cyclin encoded by Kaposi's sarcoma-associated herpesvirus stimulates cdk6 to phosphorylate the retinoblastoma protein and histone H1

D Godden-Kent, Simon Talbot, C Boshoff, Y Chang, P Moore, R A Weiss, S Mittnacht

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus 8) is a novel gammaherpesvirus implicated in the cause of Kaposi's sarcoma and certain malignancies of lymphatic origin. One of the candidate genes possibly involved in promoting tumor development is an open reading frame (ORF) with sequence similarity to human type D cyclin genes. This cyclin-like gene, when expressed in tissue culture cells, promotes phosphorylation and inactivation of the retinoblastoma tumor suppressor protein and thereby may result in deregulation of cell division control. We report here the biochemical characterization of this cyclin (KSHV-cyc) and the kinase activity that it elicits upon expression in tissue culture cells. We demonstrate that the kinase activity associated with KSHV-cyc is sensitive to the cdk inhibitor p27 (KIP) and due to activation of cdk6. However, in contrast to cdk6 activated by cellular type D cyclins, the cdk6 activated by KSHV-cyc is capable of phosphorylating not only the retinoblastoma protein but also histone H1. This finding implies that activation by KSHV-cyc alters the substrate preference of this cdk. This may have important physiological consequences in that the kinase activity triggered by this viral cyclin may abrogate cell cycle checkpoints in addition to those targeted by cellular cyclin D-cdk6 kinase.
Original languageEnglish
Pages (from-to)4193-8
Number of pages6
JournalJournal of Virology
Volume71
Issue number6
Publication statusPublished - 1997

Keywords / Materials (for Non-textual outputs)

  • Animals
  • COS Cells
  • Cell Cycle Proteins
  • Cells, Cultured
  • Cercopithecus aethiops
  • Cyclin-Dependent Kinase 6
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases
  • Cyclins
  • Dogs
  • Enzyme Activation
  • Herpesvirus 8, Human
  • Histones
  • Microtubule-Associated Proteins
  • Phosphorylation
  • Protein-Serine-Threonine Kinases
  • Retinoblastoma Protein
  • Spodoptera
  • Tumor Suppressor Proteins

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