CDI1, A HUMAN G1-PHASE AND S-PHASE PROTEIN PHOSPHATASE THAT ASSOCIATES WITH CDK2

We used the interaction trap, a yeast genetic selection for interactin g proteins, to isolate human cyclin-dependent kinase interactor 1 (Cdi 1). In yeast, Cdi1 interacts with cyclin-dependent kinases, including human Cdc2, Cdk2, and Cdk3, but not with Ckd4. In HeLa cells, Cdi1 is expressed at the G1 to S transition, and the protein forms stable comp lexes with Cdk2. Cdi1 bears weak sequence similarity to known tyrosine and dual specificity phosphatases. In vitro, Cdi1 removes phosphate f rom tyrosine residues in model substrates, but a mutant protein that b ears a lesion in the putative active site cysteine does not. Overexpre ssion of wild-type Cdi1 delays progression through the cell cycle in y east and HeLa cells; delay is dependent on Cdi1 phosphatase activity. These experiments identify Cdi1 as a novel type of protein phosphatase that forms complexes with cyclin-dependent kinases.