Research for unknown targets of cyclin-dependent kinases

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The p16INK4a tumor suppressor inhibits cyclin-dependent kinases (CDK4 and CDK6). Here we report the isolation of a novel gene, SEI-1, whose product (p34^<SEI-1>) appears to antagonize the function of p16^<INK4a>. Addition of p34^<SEI-1> to cyclin D1-CDK4 renders the complex resistant to inhibition by p16^<INK4a>. Expression of SEI-1 is rapidly induced onaddition of serum to quiescent fibroblasts, and ectopic expression of p34^<SEI-1> enables fibroblasts to proliferate even in low serum concentrations. p34^<SEI-1> seems to act as a growth factor sensor and may facilitate the formation and activation of cyclin D-CDK complexes in the face of inhibitory levels of INK4 proteins.The p16INK4a tumor suppressor inhibits cyclin-dependent kinases (CDK4 and CDK6). Here we report the isolation of a novel gene, SEI-1, whose product (p34^<SEI-1>) appears to antagonize the function of p16^<INK4a>. Addition of p34^<SEI-1> to cyclin D1-CDK4 renders the complex resistant to inhibition by p16^<INK4a> a. Expression of SEI-1 is rapidly induced on addition of serum to quiescent fibroblasts, and ectopic expression of p34^<SEI-1> enables fibroblasts to proliferate even in low serum concentrations. p34^<SEI-1> seems to act as a growth factor sensor and may facilitate the formation and activation of cyclin D-CDK complexes in the face of inhibitory levels of INK4 proteins.