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14-3-3 sigma is a p53-regulated inhibitor of G2/M progression.

Exposure of colorectal cancer (CRC) cells to ionizing radiation results in a cell-cycle arrest in G1 and G2. The G1 arrest is due to p53-mediated induction of the cyclin-dependent kinase inhibitor p21WAF1/CIP1/SDI1, but the basis for the G2 arrest is unknown. Through a quantitative analysis of gene expression patterns in CRC cell lines, we have discovered that 14-3-3 sigma is strongly induced by gamma irradiation and other DNA-damaging agents. The induction of 14-3-3 sigma is mediated by a p53-responsive element located 1.8 kb upstream of its transcription start site. Exogenous introduction of 14-3-3 sigma into cycling cells results in a G2 arrest. As the fission yeast 14-3-3 homologs rad24 and rad25 mediate similar checkpoint effects, these results document a molecular mechanism for G2/M control that is conserved throughout eukaryotic evolution and regulated in human cells by p53.

Pubmed ID: 9659898

Authors

  • Hermeking H
  • Lengauer C
  • Polyak K
  • He TC
  • Zhang L
  • Thiagalingam S
  • Kinzler KW
  • Vogelstein B

Journal

Molecular cell

Publication Data

December 24, 1997

Associated Grants

  • Agency: NCI NIH HHS, Id: CA 43460
  • Agency: NCI NIH HHS, Id: CA 57345

Mesh Terms

  • 14-3-3 Proteins
  • Colorectal Neoplasms
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA Damage
  • Enzyme Inhibitors
  • Eukaryotic Cells
  • Evolution, Molecular
  • Exonucleases
  • Exoribonucleases
  • G2 Phase
  • Gene Expression Regulation, Neoplastic
  • Growth Inhibitors
  • Humans
  • In Situ Hybridization, Fluorescence
  • Isoenzymes
  • Mitosis
  • Molecular Sequence Data
  • Neoplasm Proteins
  • Polyploidy
  • Proteins
  • RNA, Messenger
  • Tumor Cells, Cultured
  • Tumor Markers, Biological
  • Tumor Suppressor Protein p53
  • Tyrosine 3-Monooxygenase