Cyclin-dependent kinase inhibitor 1A (p21, Cip1), also known as CDKN1A, is a protein which in humans is encoded by the CDKN1A gene located on chromosome 6 (6p21.2).
This gene WAF1/CIP1 on human chromosome 6p, discovered by Wafik El-Deiry in 1993, encodes a potent/universal cyclin-dependent kinase inhibitor (CKI). The encoded protein p21(WAF1) 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. This was a major discovery in the early 1990's that revealed how cells stop dividing after being exposed to damaging agents such as radiation. In addition to growth arrest, p21 can mediate cellular senescence and one of the ways it was discovered was as a senescent cell-derived inhibitor. The p21(WAF1) protein can also interact 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. This protein was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a dramatic activation of CDK2, and may be instrumental in the execution of apoptosis following caspase activation. However, if anything p21 inhibits apoptosis and does not under any circumstances induce cell death. Two alternatively spliced variants, which encode an identical protein, have been reported.
p21(WAF1) is a CKI that directly inhibits the activity of cyclin E/CDK2 and cyclin D/CDK4 complexes. p21 functions as a regulator of cell cycle progression at S phase. The expression of p21 is controlled by the tumor suppressor protein p53. Sometimes,it is expressed without being induced by P53. This kind of induction plays a big role in p53 independent differentiation which is promoted by p21. Expression of p21 is mainly dependent on two factors 1) stimulus provided 2) type of the cell. Growth arrest by p21 can promote cellular differentiation.
The p21 protein also is important in the stress response. p21 is the major transcriptional target of the tumor suppressor gene, p53; despite this, loss-of-function mutations in p21 (unlike p53) do not accumulate in cancer nor do they predispose to cancer incidence. Mice genetically engineered to lack p21 develop normally and are not susceptible to cancer at a higher rate than wild-type mice (unlike p53 knockout mice).
Mice that lack the p21 gene gain the ability to regenerate lost appendages.
Enzymes are proteins that catalyze (i.e., increase the rates of) chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at significant rates. Since enzymes are selective for their substrates and speed up only a few reactions from among many possibilities, the set of enzymes made in a cell determines which metabolic pathways occur in that cell.
Like all catalysts, enzymes work by lowering the activation energy (Ea‡) for a reaction, thus dramatically increasing the rate of the reaction. Most enzyme reaction rates are millions of times faster than those of comparable un-catalyzed reactions. As with all catalysts, enzymes are not consumed by the reactions they catalyze, nor do they alter the equilibrium of these reactions. However, enzymes do differ from most other catalysts by being much more specific. Enzymes are known to catalyze about 4,000 biochemical reactions. A few RNA molecules called ribozymes also catalyze reactions, with an important example being some parts of the ribosome.Synthetic molecules called artificial enzymes also display enzyme-like catalysis.