Is p21 a Tumour suppressor gene?
In 1994, p21 (also known as wildtype activating factor-1/cyclin-dependent kinase inhibitory protein-1 or WAF1/CIP1) was introduced as a tumor suppressor in brain, lung, and colon cancer cells; it was shown that p21 induces tumor growth suppression through wild type p53 activity [2].
How does p21 regulate p53?
Cell cycle arrest in response to DNA damage involves protein stabilization and consequent upregulation of p53, which induces transcription of cyclin-dependent kinase inhibitor p21 (CDKN1A). We now show that p21 acts as a negative regulator of the cellular levels of p53.
Is p21 a CDK inhibitor?
p21Cip1 is a cyclin-dependent kinase (Cdk) inhibitor that is transcriptionally activated by p53 in response to DNA damage. Overexpression of P21 arrests cells in G1. Thus, p21 is not a universal inhibitor of Cdks but displays selectivity for G1/S Cdk/cyclin complexes.
Where is p21 protein produced?
p21 represents a major target of p53 activity and thus is associated with linking DNA damage to cell cycle arrest. This protein is encoded by the CDKN1A gene located on chromosome 6 (6p21. 2) in humans.
What protein does p21 bind to?
cyclin-dependent kinase inhibitor
p21 is a potent cyclin-dependent kinase inhibitor (CKI). The p21 (CIP1/WAF1) protein binds to and inhibits the activity of cyclin-CDK2, -CDK1, and -CDK4/6 complexes, and thus functions as a regulator of cell cycle progression at G1 and S phase.
How does p21 impact the cell cycle?
p21 inhibits cell cycle progression primarily through the inhibition of CDK2 activity, which is required not only for the phosphorylation of RB with the consequent release and activation of E2f-dependent gene expression, but also for the firing of replication origins and for the activity of proteins directly involved …
What does p21 do in the cell cycle?
Summary. P21 is a cell cycle inhibitor that is involved in essential cellular processes such as cell cycle arrest, apoptosis, and transcriptional regulation, as well as differentiation, senescence, and DNA repair.
Does p21 inhibit p53?
In many cell types, p53-mediated growth inhibition is dependent on induction of p21, which is an inhibitor of cyclin-dependent kinases that are required for cell cycle progression. Failure of mutant p53 proteins to transactivate p21 may lead to uncontrolled proliferation.
Does p53 bind to p21?
In the absence of cellular stress, p53 is prebound to both p21 REs within nucleosomal DNA in these cells. Treatment of cells with the DNA-damaging drug doxorubicin or the p53 stabilizing agent Nutlin-3, however, is accompanied by p53-dependent subsequent loss of nucleosomes associated with such p53 REs.