DESCRIPTION: Regulation of the cell cycle is in part mediated by the activity of the INK4 family of proteins. p18, INK4c, along with the closely related protein p19 is responsible for regulation of the activity of both cdk4 and cdk6 thereby regulating the G1→S transition. p18 functions to block the phosphorylation of the cdk proteins by CAK (MO15). Mapping to chromosome 1p32 in humans, p18 is composed of 3 exons spanning 7.5 kb of DNA with 5 kb of promoter sequence. A major cytoplasmic phosphoprotein that undergoes changes in phosphorylation in response to differentiation signals as well as cell cycle signals, p18 also appears to play a major role in controlling differentiation as well as in the maintenance of the differentiated state and the transformed phenotype. Although chromosome 1 is frequently involved in various cancers, there is no or very little evidence for deletions, rearrangements, or mutation of the p18 gene in neuroblastomas, osteosarcomas, non-small cell lung cancer, B-cell non-Hodgkin's lymphoma, ALL, or pancreatic cancers. INK4c deficient mice however will progress over time from pituitary hyperplasia to adenoma.
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