Embryonic Expression and Function of the Ink4d Cyclin D-Dependent Kinase Inhibitor.

Here we report the cloning and functional characterization of the cyclin D-dependent kinase 4 and 6 (Cdk4/6) inhibitory protein Cdkn2d/p19 of (-Ink4d). - is the only family gene highly expressed during development and its transcripts were detected maternally and during neurulation. The -Ink4d protein has 63% identity to mouse and human Cdkn2d/p19 and its function as a negative regulator of cell cycle traverse is evolutionary conserved. Indeed, -lnk4d can functionally substitute for mouse Cdkn2d in binding to mouse Cdk4 and inhibiting cyclin-D1-dependent CDK4 kinase activity. Further, enforced expression of -lnk4d arrests mouse fibroblasts in the G1 phase of the cell cycle. These findings indicate that CDKN2d/p19 is conserved through vertebrate evolution and suggest -lnk4d may contribute to the development of .