Cyclin A1 is a p53-induced gene that mediates apoptosis, G2/ M arrest, and mitotic catastrophe in renal, ovarian, and lung carcinoma cells |
| |
Authors: | A Rivera A Mavila K J Bayless G E Davis S A Maxwell |
| |
Institution: | (1) Department of Pathology and Laboratory Medicine, Texas A & M University System Health Science Center, Rm. 252, College Station, TX 77843-1114, USA |
| |
Abstract: | We were the first to identify cyclin A1 as a p53-induced gene by cDNA expression profiling of p53-sensitive and -resistant
tumor cells Maxwell S. A. and Davis G. E. (2000) Proc. Natl. Acad. Sci. USA 97, 13009–13014]. We show here that cyclin A1
can induce G2 cell cycle arrest, polyploidy, apoptosis, and mitotic catastrophe in H1299 non-small cell lung, TOV-21G ovarian,
or 786-0 renal carcinoma cells. More cdk1 protein and kinase activities were observed in cyclin A1-induced cells than in GFP
control-induced cells. Thus, cyclin A1 might mediate apoptosis and mitotic catastrophe through an unscheduled or inappropriate
activation of cdk1. Two primary renal cell carcinomas expressing mutated p53 exhibited reduced or absent expression of cyclin
A1 relative to the corresponding normal tissue. Moreover, renal carcinoma-derived mutant p53s were deficient in inducing cyclin
A1 expression in p53-null cells. Cyclin A1 but not cyclin A2 was upregulated in etoposide-treated tumor cells undergoing p53-dependent
apoptosis and mitotic catastrophe. Forced upregulation of cyclin A2 did not induce apoptosis. The data implicate cyclin A1
as a downstream player in p53-dependent apoptosis and G2 arrest.
Received 1 November 2005; received after revision 17 February 2006; accepted 13 April 2006 |
| |
Keywords: | Apoptosis mitotic catastrophe p53 cyclin A1 proline oxidase cdk1 |
本文献已被 PubMed SpringerLink 等数据库收录! |
|