Effects of p21Waf1/Cip1/Sdi1 on cellular gene expression: implications for carcinogenesis, senescence, and age-related diseases.

ABSTRACT: Induction of cyclin-dependent kinase inhibitor p21(Waf1/Cip1/Sdi1) triggers cell growth arrest associated with senescence and damage response. Overexpression of p21 from an inducible promoter in a human cell line induces growth arrest and phenotypic features of senescence. cDNA array hybridization showed that p21 expression selectively inhibits a set of genes involved in mitosis, DNA replication, segregation, and repair. The kinetics of inhibition of these genes on p21 induction parallels the onset of growth arrest, and their reexpression on release from p21 precedes the reentry of cells into cell cycle, indicating that inhibition of cell-cycle progression genes is a mechanism of p21-induced growth arrest. p21 also up-regulates multiple genes that have been associated with senescence or im

SUBMITTER: Chang BD 

PROVIDER: S-EPMC18232 | biostudies-literature | 2000 Apr

REPOSITORIES: biostudies-literature