P15(INK4B) IS A POTENTIAL EFFECTOR OF TGF-BETA-INDUCED CELL-CYCLE ARREST

TRANSFORMING growth factor-beta (TGF-beta) inhibits cell proliferation by inducing a G1-phase cell cycle arrest(1). Normal progression through G1 is promoted by the activity of the cyclin-dependent protein kinases CDK4 and CDK6 (ref. 2), which are inhibited by the protein p16(INK4). We have isolated a new member of the p16(INK4) family, p15(INK4B). p15 expression is induced similar to 30-fold in human keratinocytes by treatment with TGF-beta, suggesting that p15 may act as an effector of TGF-beta-mediated cell cycle arrest. The gene encoding p15 is located on chromosome 9 adjacent to the p16 gene at a frequent site of chromosomal abnormality in human tumours (9p21).