14-3-3.SIGMA. ARRESTS THE CELL CYCLE

摘要

Exposure of colorectal cancer (CRC) cells to ionizing radiation results in a growth arrest, with cells blocked in both the G1 and G2 phases of the cell cycle. The G1 block has been shown to be due to the 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 1.815 kb upstream of its transcription start site. Exogenous introduction of 14-3-3.sigma. into cycling cells results in a G2 block similar to that observed following irradiation. These results document a molecular mechanism for G2/M control that is regulated in human cells by p53.