DNA binding protein dbpA binds Cdk5 and inhibits its activity

Progress in the cell cycle is governed by the activity of cyclin dependent kinases (Cdks). Unlike other Cdks, the Cdk5 catalytic subunit is found most ly in differentiated neurons. Interestingly, the only known protein that ac tivates Cdk5 (i.e. p35) is expressed solely in the brain. It has been sugge sted that, besides its requirement in neuronal differentiation, Cdk5 activi ty is induced during myogenesis. However, it is not clear how this activity is regulated in the pathway that leads proliferative cells to differentiat ion. Tn order to find if there exists any Cdk5-interacting protein, the yea st two-hybrid system was used to screen a HeLa cDNA library. We have determ ined that a C-terminal 172 amino acid domain of the DNA binding protein, db pA, binds to Cdk5. Biochemical analyses reveal that this fragment (dbpA(C D elta)) strongly inhibits p35-activated Cdk5 kinase. The protein also intera cts with Cdk4 and inhibits the Cdk4/cyclin D1 enzyme. Surprisingly, dbpA(C Delta) does not bind Cdk2 in the two-hybrid assay nor does it inhibit Cdk2 activated by cyclin A. It could be that dbpA's ability to inhibit Cdk5 and Cdk5 reflects an apparent cross-talk between distinct signal transduction p athways controlled by dbpA on the one hand and Cdk5 or Cdk4 on the other. ( C) 1999 Federation of European Biochemical Societies.