Downregulation of Polo-like kinase 1 induces cellular senescence in human primary cells through a p53-dependent pathway.

Polo-like kinase 1 (PLK1) plays a key role in various stages of mitosis from entry into M phase to exit from mitosis. However, its role in cellular senescence remains to be determined. Therefore, the effects of PLK1 on cellular senescence in human primary cells were investigated. We found that expression of PLK1 decreased in human dermal fibroblasts and human umbilical vein endothelial cells under replicative senescence and premature senescence induced by adriamycin. PLK1 knockdown with PLK1 small interfering RNAs in young cells induced premature senescence. In contrast, upregulation of PLK1 in old cells partially reversed senescence phenotypes. Cellular senescence by PLK1 inhibition was observed in p16 knockdown cells but not in p53 knockdown cells. Our data suggest that PLK1 repression might result in cellular senescence in human primary cells via a p53-dependent pathway.