P27 (gene)


P27 (gene)

p27Kip1, (HUGO gene symbol CDKN1B) is a gene which lies on chromosome 12 in humans and encodes a protein which belongs to the "Cip/Kip" family of cyclin dependent kinase (Cdk) inhibitor proteins. It is often referred to as a cell cycle inhibitor protein because its major function is to stop or slow down the cell division cycle.

Biochemical Function

The p27Kip1 gene has a DNA sequence similar to other members of the "Cip/Kip" family which include the p21Cip1/Waf1 and p57Kip2 genes. In addition to this structural similarity the "Cip/Kip" proteins share the functional characteristic of being able to bind several different classes of Cyclin and Cdk molecules. For example, p27Kip1 binds to cyclin D either alone, or when complexed to its catalytic subunit CDK4. In doing so p27Kip1 inhibits the catalytic activity of Cdk4, which means that it is prevents Cdk4 from adding phosphate residues to its principal substrate, the retinoblastoma (pRb) protein. Increased levels of the p27Kip1 protein typically cause cells to arrest in the G1 phase of the cell cycle. Likewise, p27Kip1 is able to bind other Cdk proteins when complexed to cyclin subunits such as Cyclin E/Cdk2 and Cyclin A/Cdk2.

Regulation

In general, extracellular growth factors which prevent cell growth cause an increase in p27Kip1 levels inside a cell. For example, levels of p27Kip1 increase when Transforming Growth Factor β (TGF β) is present outside of epithelial cells causing a growth arrest. [ [http://www.cell.com/content/article/abstract?uid=PII0092867494905738&session= p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21] Hideo Toyoshima, Tony Hunter; Cell, Vol 78, 67-74, 15 July 1994 ] In contrast interleukin 2 (IL-2) causes p27Kip1 levels to drop in T-lymphocytes. A mutation of this gene may lead to loss of control over the cell cycle leading to uncontrolled cellular proliferation. [ [http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=8646781 A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27(Kip1)-deficient mice.] Fero ML, Rivkin M, Tasch M, Porter P, Carow CE, Firpo E, Polyak K, Tsai LH, Broudy V, Perlmutter RM, Kaushansky K, Roberts JM. "Cell". 1996 May 31;85(5):733-44. ] [ [http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=8646780 Enhanced growth of mice lacking the cyclin-dependent kinase inhibitor function of p27(Kip1)] Kiyokawa H, Kineman RD, Manova-Todorova KO, Soares VC, Hoffman ES, Ono M, Khanam D, Hayday AC, Frohman LA, Koff A. "Cell". 1996 May 31;85(5):721-32. ] [ [http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=8646779 Mice lacking p27(Kip1) display increased body size, multiple organ hyperplasia, retinal dysplasia, and pituitary tumors.] Nakayama K, Ishida N, Shirane M, Inomata A, Inoue T, Shishido N, Horii I, Loh DY, Nakayama K. "Cell". 1996 May 31;85(5):707-20. ]

ee also

*Sic1
*CDKN1B

References


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