What does the p21 protein do?
The protein p21 (also known as WAF1, CIP1 or SD11) regulates cell proliferation by inhibiting the cell cycle through the cyclin kinase pathway. It also has been shown to inhibit apoptosis induced by numerous stimuli.
How does p21 bind to CDK?
p21 binds the cyclin subunit through a conserved cyclin-binding motif 1 (Cy1), which is present in the N-terminal region. Additionally, p21 binds through redundant weak motif, Cy2, in its C-terminal region. These binding motifs are indispensable for p21-mediated inhibition of cyclin-CDK complexes.
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 …
Which Cdk is inhibited by p21?
CDK inhibition 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.
Is p21 a tumor suppressor gene or oncogene?
p21 induction has been shown to be crucial for promoting cancer cell motility and tumorigenesis [22]. Therefore, p21 can be an oncogenic protein or a tumor suppressor, depending on its localization in the cytoplasm or the nucleus, respectively [23,24].
Is p21 a proto oncogene or tumor suppressor gene?
Consequently, p21 is often misregulated in human cancers, but its expression, depending on the cellular context and circumstances, suggests that it can act as a tumour suppressor or as an oncogene (TABLE 1).
What activates p21?
The p21-dependent activation of p300–CREBBP-driven gene transcription has a significant role in regulating oestrogen receptor-α (ERα)-dependent gene expression, thereby inducing the differentiation of ERα-positive cells40.
What does p21 activated kinase do?
p21 activated kinases (PAKs) are members of a family of enzymes. They serve as targets for the small GTP binding proteins CDC42 and Rac and have been implicated in a wide range of biological activities. Members include: PAK1, regulating cell motility and morphology.
Is p21 an oncogene or tumor suppressor?
1.1. 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].