p21 (CDKN1A)

p21 (p21^Cip1), encoded by CDKN1A, is a cyclin-dependent kinase inhibitor that stops the cell cycle in G1 after DNA damage. It is the main target through which p53 arrests dividing cells.

Function

p21 binds cyclin–CDK complexes — cyclin E–CDK2 and cyclin A–CDK2 in particular — and blocks their kinase activity, which keeps RB hypophosphorylated and E2F repressed, so the cell stays in G1. It also inhibits PCNA directly, interfering with DNA replication itself. p21 was the first CDK inhibitor discovered and is a canonical transcriptional target of p53: the p53 response to DNA damage arrests the cell largely through p21. At lower levels and in the