Cell
Volume 73, Issue 3, 7 May 1993, Pages 487-497
Journal home page for Cell

Article
Functional interactions of the retinoblastoma protein with mammalian D-type cyclins

https://doi.org/10.1016/0092-8674(93)90136-EGet rights and content

Abstract

The retinoblastoma gene product (Rb) can interact efficiently with two of three D-type G1 cyclins (D2 and D3) in vitro. Binding depended upon the minimal regions of Rb necessary for its growth-suppressive activity, as well as upon the D-type cyclin sequence motif shared with Rb-binding DNA tumor virus oncoproteins. Coexpression of the three D-type cyclins with the cyclin-dependent kinase (cdk4) in insect cells generated Rb kinase activity. By contrast, cyclins D2 and D3, but not D1, activated another such kinase, cdk2. Introduction of cyclin D2 and Rb into the Rb-deficient cell line SAOS-2 led to overt Rb hyperphosphorylation, whereas Rb, expressed alone or together with cyclin D1, remained unphosphorylated. Cyclin D2-dependent phosphorylation inhibited its binding to the transcription factor E2F and reversed the Rb G1 exit block in the cell cycle. Thus, all D-type cyclins do not function equivalently, and one of them plays a major role in reversing the cycle-blocking function of a known tumor suppressor.

References (61)

  • T. Inaba et al.

    Genomic organization, chromosomal localization, and independent expression of human cyclin D genes

    Genomics

    (1992)
  • R.E. Jones et al.

    Identification of HPV-16 E7 peptides that are potent antagonists of E7 binding to the retinoblastoma suppressor protein

    J. Biol. Chem.

    (1990)
  • W.G. Kaelin et al.

    Identification of cellular proteins that can interact specifically with the TE1A-binding region of the retinoblastoma gene product

    Cell

    (1991)
  • W.G. Kaelin et al.

    Expression cloning of a cDNA encoding a retinoblastoma-binding protein with E2F-like properties

    Cell

    (1992)
  • A. Koff et al.

    Human cyclin E, a new cyclin that interacts with two members of the CDC2 gene family

    Cell

    (1991)
  • D.J. Lew et al.

    Isolation of three novel human cyclins by rescue of G1 cyclin (Cln) function in yeast

    Cell

    (1991)
  • J.W. Ludlow et al.

    SV40 large T antigen binds preferentially to an underphosphorylated member of the retinoblastoma susceptibility gene product family

    Cell

    (1989)
  • J.W. Ludlow et al.

    The retinoblastoma susceptibility gene product undergoes cell cycle-dependent dephosphorylation and binding to and release from SV40 large T

    Cell

    (1990)
  • H. Matsushime et al.

    Colony-stimulating factor 1 regulates novel cyclins during the G1 phase of the cell cycle

    Cell

    (1991)
  • H. Matsushime et al.

    Identification and properties of an atypical catalytic subunit (p34PSK-J3/cdk4) for mammalian D type G1 cyclins

    Cell

    (1992)
  • S. Mittnacht et al.

    G1S phosphorylation of the retinoblastoma protein is associated with an altered affinity for the nuclear compartment

    Cell

    (1991)
  • J. Pines et al.

    Isolation of a human cyclin cDNA: evidence for cyclin mRNA and protein regulation in the cell cycle and for interaction with p34cdc2

    Cell

    (1989)
  • S. Shirodkar et al.

    The transcription factor E2F interacts with the retinoblastoma product and a p107-cyclin A complex in a cell cycle-regulated manner

    Cell

    (1992)
  • Y. Taya et al.

    In vitro phosphorylation of the tumor suppressor gene RB protein by mitosis-specific histone H1 kinase

    Biochem. Biophys. Res. Commun.

    (1989)
  • P. Whyte et al.

    Cellular targets for transformation by the adenovirus E1A proteins

    Cell

    (1989)
  • Y. Xiong et al.

    Human D-type cyclin

    Cell

    (1991)
  • Y. Xiong et al.

    Molecular cloning and chromosomal mapping of CCND genes encoding human D-type cyclins

    Genomics

    (1992)
  • Y. Xiong et al.

    D-type cyclins associate with multiple protein kinases and the DNA replication and repair factor PCNA

    Cell

    (1992)
  • F. Ajchenbaum et al.

    Independent regulation of human D-type cyclin gene expression during G1 phase in primary human T lymphocytes

    J. Cell Biol.

    (1993)
  • S.J. Baker et al.

    Suppression of human colorectal carcinoma cell growth by wild-type p53

    Science

    (1990)
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