Nuclear accumulation of cyclin E/Cdk2 triggers a concentration-dependent switch for the destruction of p27Xic1

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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

C Swanson1, J Ross, P K Jackson

  • 1Departments of Pathology and Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305-5324, USA.

Proceedings of the National Academy of Sciences of the United States of America
|July 8, 2000
PubMed

Insights

Nuclear import of cyclin E/Cdk2 and Xic1 triggers Xic1 destruction, enabling cyclin E/Cdk2 activation. This process involves concentration-dependent phosphorylation of Xic1 by cyclin E/Cdk2, leading to its ubiquitination and degradation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Background:

  • Cyclin-dependent kinases (CDKs) control cell cycle progression.
  • CDK activity is regulated by various factors including inhibitors.
  • Localization's role in regulating cyclin E/Cdk2 and its inhibitors is not well understood.

Purpose of the Study:

  • To investigate how the localization of cyclin E/Cdk2 and its inhibitor Xic1 regulates their activity in Xenopus laevis.
  • To elucidate the mechanism of Xic1 destruction in the nucleus.

Main Methods:

  • Studied the localization, ubiquitination, and degradation of Xic1, a Xenopus homolog of p27(Kip1) and p21(CIP1).
  • Investigated the requirements for Xic1 destruction, including nuclear import, nuclear envelope formation, and cyclin E/Cdk2 activity.
  • Analyzed the role of Xic1 phosphorylation by cyclin E/Cdk2 in its degradation.

Main Results:

  • Xic1 is concentrated, ubiquitinated, and destroyed in the nucleus.
  • Xic1 destruction requires nuclear import and the activity of cyclin E/Cdk2.
  • Phosphorylation of Xic1 by cyclin E/Cdk2 is concentration-dependent and promotes its ubiquitination and destruction.
  • Nuclear accumulation of the cyclin E/Cdk2/Xic1 complex triggers a switch for Xic1 degradation.

Conclusions:

  • Nuclear import and subsequent concentration-dependent phosphorylation by cyclin E/Cdk2 are critical for Xic1 destruction.
  • This mechanism allows for the activation of cyclin E/Cdk2, promoting cell cycle progression.

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