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.

Edited by Varda Rotter Keywords:Mitotic centromere-associated kinase (MCAK/Kif2C) Cellular senescence p53 Human primary cells a b s t r a c t Mitotic centromere-associated kinase (MCAK/Kif2C) plays a critical role in chromosome movement and segregation with ATP-dependent microtubule depolymerase activity. However, its role in cellular senescence remains unclear. MCAK/Kif2C expression decreased in human primary cells under replicative and premature senescence. MCAK/Kif2C down-regulation in young cells induced premature senescence. MCAK/Kif2C overexpression in old cells partially reversed cell senescence. Senescence phenotypes by MCAK/Kif2C knockdown were observed in p16-knockdown cells, but not in p53-knockdown cells. These results suggest that MCAK/Kif2C plays an important role in the regulation of cellular senescence through a p53-dependent pathway and might contribute to tissue/organism aging and protection of cellular transformation.

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