How does p21 regulate 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 …

Is p21 a transcription factor?

p21 is also a p53 target gene that plays a relevant role in p53-induced cell cycle arrest [9], [10], [11]. Finally, p21 has been implicated in the control of transcription, through mechanisms that may be coupled to its CDK inhibition activity but also by direct association and modulation of transcription factors.

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.

Does p53 regulate p21?

p53 down-regulates CHK1 through p21 and the retinoblastoma protein.

What are the main categories of p21?

The three human p21-Ras genes encode for four proteins (Ha, N, K4A, K4B) and belong to the important small-G protein-mediated signaling family.

What is the function of p21 gene?

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.

What is p21 controlled by?

p21 is negatively regulated by ubiquitin ligases both over the course of the cell cycle and in response to DNA damage. Specifically, over the G1/S transition it has been demonstrated that the E3 ubiquitin ligase complex SCFSkp2 induces degradation of p21.

What is p53 p21 pathway?

The p53/p21 pathway plays a key role in the regulation of cell senescence process of BM-MSCs from SLE patients. These findings could explore the mechanism of cell senescence of BM-MSCs in SLE patients.

What activates p21?

Upon DNA damage or other stressors, the tumor suppressor p53 is activated, leading to transient expression of the cyclin-dependent kinase inhibitor (CKI) p21. This either triggers momentary G1 cell cycle arrest or leads to a chronic state of senescence or apoptosis, a form of genome guardianship.

How do p53 and p21 work together?

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.

What is p21 21st century skills?

P21 recommends that instruction in these subjects incorporate opportunities for students to also gain additional competencies critical for success in the 21st century: Learning and Innovation Skills (the so-called 4Cs) are Creative Thinking, Collaboration, Communication, and Critical Thinking and Problem Solving.

What is p53 and p21 genes?

Abstract. 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.

Which is the main transcriptional regulator of p21?

Regulation of p21. p53 is the main transcriptional regulator of p21. p21 contains two conserved p53 responsive elements (p53RE) in its promoter. The two p53 homologues including p63 and p73 can transactivate p21 through binding to p53RE.

What is the effect of p21 in cellular function?

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. Because of its role in these processes, a large body of research has studied its role in cancer initiation, progression, and response to therapy.

How does p53 affect the transcription of p21?

The phosphorylation of p53 on Ser 33/46 by Pin1 increases its stability resulting in increased transcriptional activity of p53 toward its target genes such as p21. Since Ser33/46 lies in the vicinity of MDM2 binding site, this rearrangement prevents p53 binding to its ubiquitin ligase MDM2 [15].

How does MKRN1 decrease transcriptional effect of p21?

Makorin Ring Finger Protein 1 (MKRN1) is an E3 ubiquitin ligase that increases p53 degradation by ubiquitination and as a consequence, this destabilization decreases transcriptional effect of p53 on p21. Furthermore, MKRN1 can directly binds to p21 and degrade this factor by polyubiqutination in a p53-independent manner [20].