CDKN1A (p21, CIP1, WAF1), a cyclin-dependent kinase inhibitor, is necessary for proper control of the cell cycle and premature senescence. p21 is a cyclin-dependent kinase (CDK) inhibitor that suppresses proliferation by inhibiting CDK2 and CDK1 activity at the G1/S and G2/M transitions. p21 is a major mediator of p53 to induce cell cycle arrest in G1. p21 can interact with proliferating cell nuclear antigen (PCNA), and plays a regulatory role in S phase DNA replication and DNA damage repair. p21 was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a dramatic activation of CDK2, and may be instrumental in the execution of apoptosis following caspase activation. Overexpression of p21 decreases the expression levels of cell cycle progression genes and upregulates senescence-inducing genes.