CDKN1A

CDKN1A encodes the protein p21, also known as p21^Cip1/Waf1, a key member of the CIP/KIP family of cyclin-dependent kinase inhibitors. The p21 protein is a 164‑amino‑acid, 21‑kDa nuclear regulator that primarily inhibits cyclin-CDK2 and cyclin-CDK4 complexes, thereby blocking cell cycle progression from G1 to S phase. It also modulates DNA replication and repair through interactions with PCNA, linking cell cycle control to genome maintenance.

Expression of CDKN1A is tightly controlled and is a central component of the p53 pathway. In response to DNA damage and other cellular stresses, p53 drives transcription of CDKN1A to induce cell cycle arrest and allow time for DNA repair. p21 can also be induced via p53‑independent mechanisms, including TGF‑β signaling and differentiation pathways. The protein is regulated post-translationally by phosphorylation, acetylation, and ubiquitination, which influence its stability and subcellular localization.

In addition to its nuclear function in checkpoint control, p21 participates in various cellular processes such as senescence, apoptosis modulation, and differentiation, with context‑dependent effects. It can act as a brake on proliferation, but in some settings its expression correlates with therapy resistance and senescent phenotypes, reflecting a complex role in cancer biology.

CDKN1A is located on chromosome 6p21.2 in humans. The gene’s product, p21, remains a subject of study for its dual roles in tumor suppression and tumor progression, its involvement in aging processes, and its potential as a biomarker or therapeutic target.