| Background |
- Members of the INK4 family of cyclin dependent kinase inhibitors include p16 INK4A, p15 INK4B, p18 INK4C, and p19 INK4D. The INK4 family members inhibit cyclin dependent kinases 4 and 6 (CDK4 and CDK6), causing cell cycle arrest in G1 phase. The INK4A-ARF-INK4B locus on chromosome 9p21, frequently lost in human cancer, encodes the INK4 family members p16 INK5A and p15 INK4B, as well as the unrelated protein, ARF.
- p15 INK4B protein expression is induced by TGF-β in human keratinocytes, a process which requires demethylation at the p15 INK4B locus. In hematopoietic cells, p15 INK4B signaling functions in the determination of cell fate.
- Researchers have shown that expression levels of p15 INK4B, altered by epigenetic modification, have an impact on disease progression in multiple myeloma. Similarly, studies in pancreatic cancer have shown hypermethylation and epigenetic silencing of p15 INK4B, p16 INK4A, and CDK inhibitors p21cip1 and p27kip1.
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