• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


DNA damage-induced activation of p53 by the checkpoint kinase Chk2.

Chk2 is a protein kinase that is activated in response to DNA damage and may regulate cell cycle arrest. We generated Chk2-deficient mouse cells by gene targeting. Chk2-/- embryonic stem cells failed to maintain gamma-irradiation-induced arrest in the G2 phase of the cell cycle. Chk2-/- thymocytes were resistant to DNA damage-induced apoptosis. Chk2-/- cells were defective for p53 stabilization and for induction of p53-dependent transcripts such as p21 in response to gamma irradiation. Reintroduction of the Chk2 gene restored p53-dependent transcription in response to gamma irradiation. Chk2 directly phosphorylated p53 on serine 20, which is known to interfere with Mdm2 binding. This provides a mechanism for increased stability of p53 by prevention of ubiquitination in response to DNA damage.

Pubmed ID: 10710310


  • Hirao A
  • Kong YY
  • Matsuoka S
  • Wakeham A
  • Ruland J
  • Yoshida H
  • Liu D
  • Elledge SJ
  • Mak TW


Science (New York, N.Y.)

Publication Data

March 10, 2000

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM44664

Mesh Terms

  • Animals
  • Apoptosis
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins
  • Checkpoint Kinase 2
  • DNA Damage
  • DNA-Binding Proteins
  • G1 Phase
  • G2 Phase
  • Gamma Rays
  • Gene Expression Regulation
  • Gene Targeting
  • Genes, Tumor Suppressor
  • Genes, p53
  • Humans
  • Interphase
  • Mice
  • Nuclear Proteins
  • Phosphorylation
  • Phosphoserine
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-mdm2
  • Stem Cells
  • T-Lymphocytes
  • Transcription, Genetic
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins