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 p21<WAF1/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.
申请公布号
WO9931240(A2)
申请公布日期
1999.06.24
申请号
WO1998US26924
申请日期
1998.12.18
申请人
THE JOHNS HOPKINS UNIVERSITY;HERMEKING, HEIKO;VOGELSTEIN, BERT;KINZLER, KENNETH, W.
发明人
HERMEKING, HEIKO;VOGELSTEIN, BERT;KINZLER, KENNETH, W.