Complete inhibition of Cdk/cyclin by one molecule of p21(Cip1)

Ludger Hengst, Ulrich Göpfert, Hilal A. Lashuel, Steven I. Reed

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

Cell-cycle phase transitions are controlled by cyclin-dependent kinases (Cdks). Key to the regulation of these kinase activities are Cdk inhibitors, proteins that are induced in response to various antiproliferative signals but that can also oscillate during cell-cycle progression, leading to Cdk inactivation. A current dogma is that kinase complexes containing the prototype Cdk inhibitor p21 transit between active and inactive states, in that Cdk complexes associated with one p21 molecule remain active until they associate with additional p21 molecules. However, using a number of different techniques including analytical ultracentrifugation of purified p21/cyclin A/Cdk2 complexes we demonstrate unambiguously that a single p21 molecule is sufficient for kinase inhibition and that p21-saturated complexes contain only one stably bound inhibitor molecule. Even phosphorylated forms of p21 remain efficient inhibitors of Cdk activities. Therefore the level of Cdk inactivation by p21 is determined by the fraction of kinase complexed with the inhibitor and not by the stoichiometry of inhibitor bound to the kinase or the phosphorylation state of the Cdk inhibitor.

Original languageEnglish
Pages (from-to)3882-3888
Number of pages7
JournalGenes and Development
Volume12
Issue number24
Publication statusPublished - 15 Dec 1998
Externally publishedYes

Fingerprint

Cyclins
Phosphotransferases
Cyclin-Dependent Kinases
Cell Cycle
Cyclin A
Ultracentrifugation
Phase Transition
Phosphorylation

Keywords

  • Cell cycle
  • Cyclin-dependent kinase
  • Cyclin-dependent kinase inhibitor
  • P21(Cip1)

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Hengst, L., Göpfert, U., Lashuel, H. A., & Reed, S. I. (1998). Complete inhibition of Cdk/cyclin by one molecule of p21(Cip1). Genes and Development, 12(24), 3882-3888.

Complete inhibition of Cdk/cyclin by one molecule of p21(Cip1). / Hengst, Ludger; Göpfert, Ulrich; Lashuel, Hilal A.; Reed, Steven I.

In: Genes and Development, Vol. 12, No. 24, 15.12.1998, p. 3882-3888.

Research output: Contribution to journalArticle

Hengst, L, Göpfert, U, Lashuel, HA & Reed, SI 1998, 'Complete inhibition of Cdk/cyclin by one molecule of p21(Cip1)', Genes and Development, vol. 12, no. 24, pp. 3882-3888.
Hengst L, Göpfert U, Lashuel HA, Reed SI. Complete inhibition of Cdk/cyclin by one molecule of p21(Cip1). Genes and Development. 1998 Dec 15;12(24):3882-3888.
Hengst, Ludger ; Göpfert, Ulrich ; Lashuel, Hilal A. ; Reed, Steven I. / Complete inhibition of Cdk/cyclin by one molecule of p21(Cip1). In: Genes and Development. 1998 ; Vol. 12, No. 24. pp. 3882-3888.
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