p21
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Cyclin-dependent kinase inhibitor 1A (p21, Cip1), also known as CDKN1A, is a human gene.
This gene encodes a potent cyclin-dependent kinase inhibitor. The encoded protein 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 protein can 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. Two alternatively spliced variants, which encode an identical protein, have been reported.[1]
p21, also known as cyclin-dependent kinase inhibitor 1A or CDKN1A, is a human gene on chromosome 6 (location 6p21.2), that encodes a cyclin-dependent kinase inhibitor that directly inhibits the activity of cyclin-CDK2 and cyclin-CDK4 complexes. p21 functions as a regulator of cell cycle progression at S phase[2]. The expression of p21 is controlled by the tumor suppressor protein p53.
The function of this gene relates in part to stress response [3]. 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. In fact, mice genetically engineered to lack p21, develop rather normally and are not susceptible to cancer (again, unlike p53).
p21 also mediates the resistance of hematopoietic cells to an infection with HIV [4] by complexing with the HIV integrase and thereby aborting chromosomal integration of the provirus.
[edit] External links
[edit] References
- ^ Entrez Gene: CDKN1A cyclin-dependent kinase inhibitor 1A (p21, Cip1).
- ^ A. L. Gartel and S. K. Radhakrishnan (2005) "Lost in transcription: p21 repression, mechanisms, and consequences" in Cancer Research Volume 65, pages 3980-3985. Entrez PubMed 15899785
- ^ R. Rodriguez and M. Meuth. (2006) "Chk1 and p21 cooperate to prevent apoptosis during DNA replication fork stress" in Molecular Biology of the Cell Volume 17, pages 402-412. Entrez PubMed 16280359
- ^ Zhang J, Scadden DT, Crumpacker CS.: Primitive hematopoietic cells resist HIV-1 infection via p21. J Clin Invest. 2007 Feb 1;117(2):473-481. PMID 17273559
[edit] Further reading
- Marone M, Bonanno G, Rutella S, et al. (2003). "Survival and cell cycle control in early hematopoiesis: role of bcl-2, and the cyclin dependent kinase inhibitors P27 and P21.". Leuk. Lymphoma 43 (1): 51–7. PMID 11908736.
- Fang JY, Lu YY (2002). "Effects of histone acetylation and DNA methylation on p21( WAF1) regulation.". World J. Gastroenterol. 8 (3): 400–5. PMID 12046058.
- Tokumoto M, Tsuruya K, Fukuda K, et al. (2003). "Parathyroid cell growth in patients with advanced secondary hyperparathyroidism: vitamin D receptor and cyclin-dependent kinase inhibitors, p21 and p27.". Nephrol. Dial. Transplant. 18 Suppl 3: iii9–12. PMID 12771291.
- Amini S, Khalili K, Sawaya BE (2004). "Effect of HIV-1 Vpr on cell cycle regulators.". DNA Cell Biol. 23 (4): 249–60. doi:. PMID 15142382.
- Zhang Z, Wang H, Li M, et al. (2006). "Novel MDM2 p53-independent functions identified through RNA silencing technologies.". Ann. N. Y. Acad. Sci. 1058: 205–14. doi:. PMID 16394138.
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