How does p21 induce apoptosis?

How does p21 induce apoptosis?

p21 induction primarily inhibits apoptosis by causing cell cycle arrest and DNA repair. However, p21-arrested cells may be triggered to undergo apoptosis following activation of pro-apoptotic genes in a p53-dependent or -independent manner1.

What is the role of p21 in cells?

p21 has a significant role in modulating DNA repair processes. First, by inhibiting cell cycle progression, p21 allows DNA repair to proceed while inhibiting apoptosis. Secondly, p21 can compete for PCNA binding with several PCNA-reliant proteins that are directly involved in DNA repair processes9 (FIG.

How does p21 inhibit apoptosis?

A, p21 may block apoptosis by interacting with proapoptotic molecules such as procaspase-3, caspase-8, and the kinase apoptosis signal-regulating kinase 1 (ASK1) or by inducing cell cycle arrest after binding to cyclin E/Cdk2 complexes or by binding to cyclin A/Cdk2 complexes.

What is the role of p21 in the G1 S transition?

The data show that at physiological levels of accumulation, p21, in addition to its role in negatively regulating the G1/S transition, contributes to regulation of the G2/M transition. Both G1- and G2-arrested cells were observed in all cell types, with different preponderances.

How is p21 function altered in cancerous cells?

p21 was shown to be responsible for protecting tumor cells from DNA damage cytotoxic effect after Chk1 inhibition. p21 activated kinase (PAK) proteins, have different functions in different species; these proteins are associated with cancer due to their role in cell survival, cell migration, and proliferation [100].

What happens when p21 is mutated?

The p21 gene, a downstream effector of the p53 tumor suppressor gene is involved in breast carcinogenesis and in other malignancies. The mutational and hypermethylation profile of the p21 gene in the north Indian population revealed that they are associated with breast cancer development and progression.

How does p21 regulate the cell cycle?

P21 has been found to promote cell cycle arrest following activation from various stimuli. It is known to inhibit the cell cycle progression, leading to cell cycle arrest. A major cause of p21 activation leading to this outcome is the presence of damaging agents.

Is p21 a tumor 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?

Following activation of p53, for example by viral infection or induction of DNA damage, p21 expression is upregulated. High levels of p21 then result in RB-E2F complex formation and downregulation of a large number of cell cycle genes. Thus, p53-dependent transcriptional repression is indirect.

Is p21 a tumor suppressor protein?

The cyclin-dependent kinase inhib- itor p21 is a major effector of the tumour suppressor p53. It mediates cell cycle arrest in the G1 phase and cell senescence in response to several stimuli, including oncogene-induced proliferation.

Where is p21 in the cell?

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.

What is p21 promoter?

The p21 promoter has two p53 binding sites (or response elements, REs) that conform to the p53 consensus binding sequence (Fig. 1A), the more distal (5′) site at -2283 that binds p53 relatively strongly and the more proximal (3′) site at -1391 that is more weakly bound by p53 (12–14).

What is the difference in functionality between p53 and p21?

The key difference between p53 and p21 is that p53 arrests the cell growth by holding the cell cycle at the G1/S regulation point upon detecting DNA damage, while p21 binds to G1-S/CDK complexes upon induction by p53 and inhibits the activity of CDK complexes.

Why is p21 a tumor suppressor gene?

What does p21 peptide 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.