Open Accessp53 Transactivation and Protein Accumulation Are Independently Regulated by UV Light in Different Phases of the Cell Cycle
Author(s) -
Tarja Haapajärvi,
Kimmo Pitkänen,
Minna Tsubari,
Marikki Laiho
Publication year - 1997
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.17.6.3074
Subject(s) - transactivation , biology , cell cycle , gadd45 , dna damage , dna replication , microbiology and biotechnology , gene , dna , retinoblastoma protein , gene expression , cell cycle checkpoint , genetics
DNA damage-induced activation of the p53 tumor suppressor gene is suggested to be central in the cellular damage response pathway. In this study, we analyzed the responses of p53 to UVC radiation in synchronized mouse fibroblasts in terms of p53 accumulation, transcriptional activation, and sequence-specific DNA-binding activity. UVC was found to induce accumulation of p53 cell cycle dependently in G1/S- and S-phase cells but not in G0 or G1 cells. In contrast, p53 transcriptional activity and its target genes, p21 and GADD45, were stimulated by UVC in G0 and G1 cells in the absence of detectable p53 protein. The accumulation of p53 and increased p21 and GADD45 expression were replication dependent in S-phase cells. Interestingly, sequence-specific p53 DNA-binding activity was stimulated also replication independently in S phase, though the effect was not conveyed to stimulation of p53 target genes, suggesting that additional events are required for p53-stimulated gene expression. The results show that opposed to the cell cycle dependence of p53 accumulation, the UVC-mediated transactivation by p53 is independent of the cell cycle phase and protein stabilization.