Isolation of the human cdk2 gene that encodes the cyclin A- and adenovirus E1A-associated p33 kinase

Abstract

CYCLINS are regulatory subunits which associate with kinases to form complexes that control many of the important steps in cell-cycle progression. The best characterized of the cyclin-containing complexes is the association of cyclin B with the p34^cdc2 kinase. The p34^cdc2/cyclin B complex is required for the G2 to M transition (see refs 1–4 for review), but the physiological role of other cyclin complexes is unclear. Human cyclin A binds independently to two kinases, associating with either p34^cdc2 or a related protein, p33 (refs 5–7). In adenovirus-transformed cells, the viral E1 A oncoprotein seems to associate with p33/cyclin A but not with P34^cdc2/cyclin A (B. Faha, M.M., L-H.T. and E.H., manuscript submitted). To isolate the gene for p33, we have cloned several novel human cdc2-related genes. The protein product of one of these genes, cdk2 (cyclin-dependent kinase 2), shares 65% sequence identity with p34^cdc2 (ref. 8) and 89% identity with the Xenopus Eg-1 gene product⁹. Immmunochemical characterization and partial proteolytic mapping show that the cdk2 gene product is the cyclin A-associated p33. Immunoprecipitations of the p33^cdk2 protein suggest that it can act as a protein kinase in vitro. As p33^cdk2 is bound to cyclin A and is targeted by the viral El A protein, we suggest that the p33^cdk2/cyclin A complex has a unique role in cell-cycle regulation of vertebrate cells.