Distinct versus redundant properties among members of the INK4 family of cyclin-dependent kinase inhibitors

p16(INK4a), p15(INK4b), pig(INK4c) and p19(INK4d) comprise a family of cycl in-dependent kinase inhibitors and tumor suppressors, We report that the IN K4 proteins share the ability to arrest cells in G1, and interact with CDK4 or CDK6 with similar avidity, In contrast, only p18 and particularly p19 a re phosphorylated in vivo, and each of the human INK4 proteins shows unique expression patterns dependent on cell and tissue type, and differentiation stage. Thus, the INK4 proteins harbor redundant as well as non-overlapping properties, suggesting distinct regulatory modes, and diverse roles for th e individual INK4 family members in cell cycle control, cellular differenti ation: and multistep oncogenesis. (C) 2000 Federation of European Biochemic al Societies.