Deffie A, Hao M, Montes de Oca Luna R, Hulboy D L, Lozano G
Department of Molecular Genetics, M. D. Anderson Cancer Center, University of Texas, Houston 77030, USA.
Mol Cell Biol. 1995 Jul;15(7):3926-33. doi: 10.1128/MCB.15.7.3926.
The wild-type p53 protein is a potent growth suppressor when overexpressed in vitro. It functions as a transcriptional activator and causes growth arrest at the G1/S stage of the cell cycle. We monitored p53 transactivation as an indicator of p53 function throughout the cell cycle. We first demonstrate that cells which exhibited contact inhibition of growth lacked p53 transactivation function at high cell density. Since these cells were noncycling, we examined whether the ectopic expression of any cyclin could override contact inhibition of growth and restore p53 transactivation function. The transfection of cyclin E at high cell density stimulated the progression of cells through the cell cycle and restored p53 transactivation function. The transcriptional activity of p53 induced by cyclin E was regulated at the level of DNA binding. Cells that did not show contact inhibition of growth had a functional p53 regardless of cell density. Thus, contact inhibition of cell growth corresponded to a lack of p53 transactivation function and the overexpression of cyclin E in these contact-inhibited cells stimulated cell cycle progression and resulted in p53 transcriptional activity.
野生型p53蛋白在体外过表达时是一种有效的生长抑制因子。它作为转录激活因子发挥作用，并导致细胞周期在G1/S期停滞。我们监测p53的反式激活作用，以此作为整个细胞周期中p53功能的指标。我们首先证明，表现出生长接触抑制的细胞在高细胞密度时缺乏p53反式激活功能。由于这些细胞不进行细胞周期循环，我们研究了任何细胞周期蛋白的异位表达是否能克服生长接触抑制并恢复p53反式激活功能。在高细胞密度下转染细胞周期蛋白E可刺激细胞通过细胞周期进程，并恢复p53反式激活功能。细胞周期蛋白E诱导的p53转录活性在DNA结合水平受到调控。未表现出生长接触抑制的细胞无论细胞密度如何都具有功能性p53。因此，细胞生长接触抑制对应于p53反式激活功能的缺失，而在这些接触抑制的细胞中过表达细胞周期蛋白E可刺激细胞周期进程并导致p53转录活性。
