G1 control in mammalian cells

S. I. Reed, E. Bailly, V. Dulic, L. Hengst, D. Resnitzky, J. Slingerland

Research output: Contribution to journalArticle

143 Scopus citations

Abstract

Cyclin-dependent kinases (Cdks) control the major cell cycle transitions in eukaryotic cells. On the basis of a variety of experiments where cyclin function either is impaired or enhanced, D-type cyclins as well as cyclins E and A have been linked to G1 and G1/S phase roles in mammalian cells. We therefore sought to determine if agents that block the G1/S phase transition do so at the level of regulating the Cdk activities associated with these cyclins. A variety of conditions that lead to G1 arrest were found to correlate with accumulation of G1-specific Cdk inhibitors, including treatment of fibroblasts with ionizing radiation, treatment of epithelial cells with TGF-beta, treatment of HeLa cells with the drug lovastatin, and removal of essential growth factors from a variety of different cell types. Mechanistically, inhibition of Cdks was found to involve the stoichiometric binding of Cdk inhibitor proteins. p21Waf1/Cip1 was associated with DNA damage induced arrest while p27Kip1/p28Ick1 accumulated under a variety of antiproliferative conditions.

Original languageEnglish (US)
Pages (from-to)69-73
Number of pages5
JournalJournal of Cell Science
Volume107
Issue numberSUPPL. 18
StatePublished - Dec 1 1994
Externally publishedYes

Keywords

  • Cdk
  • Cell cycle
  • Cyclin
  • G

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    Reed, S. I., Bailly, E., Dulic, V., Hengst, L., Resnitzky, D., & Slingerland, J. (1994). G1 control in mammalian cells. Journal of Cell Science, 107(SUPPL. 18), 69-73.