P27 (gene)

Template:DISPLAYTITLE:p27 (gene) p27^Kip1, (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.

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Biochemical Function

The p27^Kip1 gene has a DNA sequence similar to other members of the "Cip/Kip" family which include the p21^Cip1/Waf1 and p57^Kip2 genes. In addition to this structural similarity the "Cip/Kip" family members share the functional characteristic of being capable of binding to several different classes of Cdk molecules. For example, p27^Kip1 binds to cyclin D either alone, or when complexed to its catalytic subunit CDK4. In doing so p27^Kip1 prevents 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 p27^Kip1 protein typically cause cells to arrest in the G1 phase of the cell cycle. Likewise, p27^Kip1 is able to bind other Cdk proteins when complexed to cyclin subunits such as Cyclin E/Cdk2 and Cyclin A/Cdk1.

Regulation

In general, extracellular growth factors which prevent cell growth cause an increase in p27^Kip1 levels inside a cell. For example, levels of p27^Kip1 increase when Transforming Growth Factor β (TGF β) is present outside of epithelial cells causing a growth arrest.^[1] In contrast interleuin 2 (IL-2) causes p27^Kip1 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. ^{[2] [3] [4]}

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