14-3-3 sigma is a p53-regulated inhibitor of G2/M progression.
Journal:
Mol. Cell 1997 DecAuthors:
Hermeking H, Lengauer C, Polyak K, He TC, Zhang L, Thiagalingam S, Kinzler KW, Vogelstein B
Abstract
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-r
...[more]esponsive 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.[less]
Mesh Headings:
14-3-3 Proteins, Colorectal Neoplasms, Cyclin-Dependent Kinase Inhibitor p21, Cyclins, DNA Damage, Enzyme Inhibitors, Eukaryotic Cells, Evolution, Molecular, Exonucleases, 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