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Cell biology

p21 (CDKN1A)

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p21, encoded by CDKN1A (cyclin-dependent kinase inhibitor 1A), is a potent inhibitor of cyclin-CDK complexes — particularly CDK2 — that enforces G1 and S phase cell-cycle arrest in response to p53 activation, DNA damage and other stressors. By halting replication in damaged cells, p21 provides time for repair; if damage is irreparable, sustained p21 expression can stabilise the senescent state. p21 levels rise with age in multiple tissues and its expression is used as one biomarker of the senescent cell burden, though p21 induction is not exclusive to senescence and can be context-dependent. Genetic experiments in mice show that modulating CDKN1A influences both cancer susceptibility and tissue homeostasis in opposing directions, underscoring its context-dependent biology.

Sources

  1. El-Deiry WS, Tokino T, Velculescu VE, et al.. (1993). WAF1, a potential mediator of p53 tumor suppression. *Cell*doi:10.1016/0092-8674(93)90500-P
  2. Noda A, Ning Y, Venable SF, Pereira-Smith OM, Smith JR. (1994). Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen. *Experimental Cell Research*doi:10.1006/excr.1994.1063