Many studies suggested that extrinsic stimuli could lead to DNA damage which activates p53 as well as its downstream transcriptional target p21 directly, who further induces Rb dephosphorylation and results in cell cycle arrest.13,41 In addition to p53-p21 signaling, the p16-Rb pathway is also involved in cellular senescence.11–13 There is a view that p21 is activated upon entry into early senescence, while p16 is activated at a later stage, which might partially explain the unchanged p16 expression in the acute phase of cisplatin-induced kidney injury.11 The gene discussed is CDKN2A; the disease is kidney injury.