FIGURE 1.

Regulation of p53 activity by FBXO22 during senescence. All known senescence‐inducing stimuli activate p53 through DNA damage responses (DDR). Activated p53 then transcriptionally induces FBXO22. An increase in FBXO22 complexed with SCF and KDM4A targets methylated p53 for ubiquitylation. Acetylation of p53 by CBP/p300 and PHF20 binding to methylated p53 suppresses SCF‐FBXO22‐KDM4A mediated ubiquitylation of p53. Ubiquitylated p53 is degraded through a proteasome pathway. Downregulation of p53 activity at the late phase of senescence triggers the induction of p16 and SASP, the former being essential for durable cessation of cell proliferation and the latter causing acceleration in aging phenotypes through induction of tissue microinflammation