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Proteolysis of Xenopus Cip-type CDK inhibitor, p16Xic2, is regulated by PCNA binding and CDK2 phosphorylation

Xi-Ning Zhu1, Dong Hyun Kim, Horng-Ru Lin

  • 1Department of Molecular Medicine, Institute of Biotechnology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. yew@uthscsa.edu.

Cell Division
|April 24, 2013
PubMed
Abstract

Insights

Xenopus Xic2 protein turnover is regulated by DNA, PCNA, and CDK2 phosphorylation during interphase. Xic3 remains stable, suggesting unique roles for these cell division regulators.

Area of Science:

  • Cell biology
  • Molecular biology
  • Developmental biology

Background:

  • Cell division is regulated by cyclin-dependent kinases (CDKs) and CDK inhibitors.
  • Xenopus laevis has three CDK inhibitors: Xic1, Xic2, and Xic3, with known regulation for Xic1 but limited knowledge for Xic2 and Xic3.

Purpose of the Study:

  • To investigate the regulation of Xenopus Xic2 by proteolysis and phosphorylation.
  • To understand the differential regulation of Xenopus CDK inhibitors Xic1, Xic2, and Xic3.

Main Methods:

  • Utilized Xenopus interphase egg extract as a model system.
  • Examined proteolysis and phosphorylation of Xic2.
  • Assessed Xic3 stability in the presence or absence of DNA.

Main Results:

  • Xic2 undergoes DNA- and PCNA-dependent ubiquitin-mediated proteolysis, promoted by Cdt2.
  • CDK2 phosphorylates Xic2 at Ser-98 and Ser-131, inhibiting its turnover.
  • Xic2 is phosphorylated by a caffeine-sensitive kinase at Ser-78 and Ser-81 in response to DNA damage, without altering turnover.
  • Xic3 is stable and not phosphorylated in Xenopus interphase egg extract.

Conclusions:

  • Xic2 proteolysis during interphase is regulated by DNA, PCNA, and CDK2 phosphorylation.
  • Xic2 phosphorylation by a caffeine-sensitive kinase may be involved in DNA damage response.
  • Xic1, Xic2, and Xic3 exhibit unique regulatory mechanisms, potentially reflecting specialized functions in cell division and development.

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