Cyclins regulate transitions between cell cycle phases by acting as regulatory subunits of the cyclin-dependent kinases (cdk). The temporal expression of cyclins is tightly regulated and plays a critical role in controlling the enzymatic activity of the cdks. Cyclin-dependent kinase 2 (Cdk2) is a member of a family of cdc2-related cell cycle protein kinases. Cdk2 is expressed earlier in the cell cycle than cdc2 and forms complexes with cyclins A, E, D1, and D3. It is not known if the D cyclins can form active complexes with Cdk2. Cyclin E-Cdk2 kinase is active in the G1 and S phases of the cell cycle and is important, as is Cyclin A-Cdk2, for the progression from G1 to S phase. One substrate for cyclin E-Cdk2 is a Nuclear Protein mapped to the Ataxia Telangiectasia locus, NPAT. This protein associates with cyclin E-Cdk2 and can be phosphorylated by Cdk2. NPAT protein levels peak at the G1/S boundary and overexpression of NPAT accelerates S phase entry, especially after coexpression of cyclin E-Cdk2. Thus, NPAT is a substrate of cyclin E-Cdk2 that may mediate G1 to S phase transition.