The cell cycle and how it is steered by Kaposi's sarcoma-associated herpesvirus cyclin.
A timely coordination of cellular DNA synthesis and division cycles is governed by the temporal and spatial activation of cyclin-dependent kinases (Cdks). The primary regulation of Cdk activation is through binding to partner cyclin proteins. Several gammaherpesviruses encode a viral homologue of cellular cyclin D, which may function to deregulate host cell cycle progression. One of these is encoded by Kaposi's sarcoma-associated herpesvirus (KSHV) and is called K cyclin or viral cyclin (v-cyclin). v-Cyclin is expressed in most of the malignant cells that are associated with KSHV infection in humans, labelling v-cyclin as a putative viral oncogene. Here are described some of the major structural and functional properties of mammalian cyclin/Cdk complexes, some of which are phenocopied by v-cyclin. In addition, the molecular events leading to orderly progression through the G(1)/S and G/M cell cycle phases are reviewed. This molecular picture serves as a platform on which to explain v-cyclin-specific functional properties. Interesting but largely speculative issues concern the interplay between v-cyclin-mediated cell cycle deregulation and molecular progression of KSHV-associated neoplasms.
Verschuren
Emmy W
EW
Stanford University, Pathology Department, 300 Pasteur Drive, MC 5324, Stanford, CA 94305, USA.
Jones
Nic
N
Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester M20 4BX, UK.
Evan
Gerard I
GI
Cancer Research Institute and Department of Cellular and Molecular Pharmacology, University of California San Francisco, CA 94143-0875, USA.
D000818:Animals; D020134:Catalytic Domain; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D018844:Cyclin-Dependent Kinases; D016213:Cyclins / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology; D050684:E2F Transcription Factors; D004789:Enzyme Activation; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D008938:Mitosis; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D014764:Viral Proteins
D018797:Cell Cycle Proteins; D016213:Cyclins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D014764:Viral Proteins; D018844:Cyclin-Dependent Kinases