Cyclin-dependent kinase inhibitor 1A (p21) (CDKN1A)

Cyclin-dependent kinase inhibitor 1A (CDKN1A), widely known as p21, is a critical regulator of the cell cycle and a primary mediator of p53-dependent cell cycle arrest [1, 2]. It functions by binding to and inhibiting the activity of cyclin-CDK2, -CDK1, and -CDK4/6 complexes, which effectively blocks the transition from G1 to S phase and prevents DNA replication [3, 6]. Beyond its role in cell cycle inhibition, p21 is involved in DNA repair through its interaction with Proliferating Cell Nuclear Antigen (PCNA) and plays a significant role in the induction of cellular senescence [1, 4]. In many human cancers, the CDKN1A regulatory axis is disrupted, often due to mutations in the upstream p53 gene, leading to genomic instability and unchecked proliferation [3]. Therapeutic strategies involving the CDKN1A axis frequently focus on restoring its expression through p53 activators or MDM2 inhibitors, such as Idasanutlin, to restore growth control [3, 5]. Conversely, in certain contexts like fibrosis or specific resistant cancers, small molecule inhibitors of p21 like UC2288 are being investigated to overcome its pro-survival effects [5]. The protein's intrinsically disordered nature makes direct small-molecule targeting challenging, yet it remains a high-priority node in oncology and aging research [1, 3]. References: [1] UniProt (P38936); [2] NCBI Gene (1026); [3] Abbas T, Dutta A. Nat Rev Cancer. 2009; [4] Kreis NN, et al. Cancers. 2019; [5] Wettersten HI, et al. Cancer Res. 2013; [6] StatPearls, 'Cell Cycle Control'.

Other names

p21CIP1WAF1CAP20SDI1CDKN1

Inhibition of cyclin-dependent kinase complexes (CDK1, CDK2, CDK4/6) and interaction with PCNA to arrest cell cycle progression [1, 3, 6].