Question

What purpose does CDKN1A serve in the cell? What role does it play with p53?

Answer 1

cyclin-dependent kinase inhibitor 1A, plays a critical role in the cellular response to DNA damage, and its overexpression results in cell cycle arrest.

CDKN1A protein binds to and inhibits the activity of cyclin-CDK2 or -CDK4 complexes, and thus functions as a regulator of cell cycle progression at G1. The expression of this gene is tightly controlled by the tumor suppressor protein p53, through which this protein mediates the p53-dependent cell cycle G1 phase arrest in response to a variety of stress stimuli.

CDKN1A protein also interacts with proliferating cell nuclear antigen (PCNA), a DNA polymerase accessory factor, and plays a regulatory role in S phase DNA replication and DNA damage repair.

CDKN1A was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a dramatic activation of CDK2, and is instrumental in the execution of apoptosis following caspase activation.

Both p53 and CDKN1A are thought to play major roles in the development of human malignancy. Upregulation of CDKN1A protein following ionizing radiation is dependent on p53 and CDKN1A mediates cell cycle arrest in response to the p53 checkpoint pathway. The expression of this gene is tightly controlled by the tumor suppressor protein p53, through which this protein mediates the p53-dependent cell cycle G1 phase arrest in response to a variety of stress stimuli. This was a major discovery in the early 1990s that revealed how cells stop dividing after being exposed to damaging agents such as radiation.