Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

Activation of cyclin e/cdk2 is coupled to site-specific autophosphorylation and ubiquitin-dependent degradation of cyclin e

Academic Article
uri icon
  • Overview
  • Research
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Won, K. A.
  • Reed, Steven

publication date

  • August 1996

journal

  • EMBO Journal  Journal

abstract

  • A yeast screen was developed to identify mutations in human cyclin E that lead to stabilization of the protein in order to identify determinants important for cyclin E turnover. Both C-terminal truncations and missense mutations near the C-terminus of cyclin E conferred hyperstability in vivo, suggesting that sequences in this region were critical for turnover. The following observations indicate that autophosphorylation of CDK2/cyclin E on Thr380 of the cyclin regulates cyclin E destruction: (i) mutation of Thr380 to Ala stabilizes cyclin E in yeast and mammalian cells; (ii) cyclin E/CDK2 autophosphorylates on cyclin E in vitro and cyclin E is a phosphoprotein in vivo in mammalian cells; (iii) the T380A mutation eliminates phosphorylation on the same site in mammalian cells and in vitro; (iv) inhibiting CDK2 activity in vivo stabilizes cyclin E; (v) the T380A mutation prevents ubiquitination of cyclin E. These results suggest a model where activation of cyclinE/CDK2 is coupled to cyclin E turnover via site-specific phosphorylation, which acts as a signal for ubiquitination and proteasome processing.

subject areas

  • Animals
  • CDC2-CDC28 Kinases
  • CDC28 Protein Kinase, S cerevisiae
  • Cells, Cultured
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases
  • Cyclins
  • DNA, Complementary
  • Fibroblasts
  • Fungal Proteins
  • G1 Phase
  • Gene Library
  • Genetic Complementation Test
  • Humans
  • Mutagenesis
  • Phosphorylation
  • Phosphothreonine
  • Protein Processing, Post-Translational
  • Protein-Serine-Threonine Kinases
  • Rats
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae
  • Transfection
  • Ubiquitins
scroll to property group menus

Research

keywords

  • G(1) cyclins
  • cyclin E
  • phosphorylation
  • turnover
  • ubiquitination
scroll to property group menus

Identity

PubMed Central ID

  • PMC452142

International Standard Serial Number (ISSN)

  • 0261-4189

PubMed ID

  • 8861947
scroll to property group menus

Additional Document Info

start page

  • 4182

end page

  • 4193

volume

  • 15

issue

  • 16

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support