ABSENCE OF CYCLIN-D CDK COMPLEXES IN CELLS LACKING FUNCTIONAL RETINOBLASTOMA PROTEIN

Cyclins D1, D2 and D3 are thought to function in the G1 phase of the c ell division cycle by regulating the activity of cyclin-dependent prot ein kinases. All three D-type cyclins can be shown to associate with t wo specific kinases, cdk4 and cdk6, providing at least six possible co mbinations. To establish whether different cell types require differen t subsets of these complexes and whether they are altered in tumours w here D-cyclin expression is perturbed, we surveyed a series of tumour cell lines and compared them where possible to non-tumorigenic counter parts. Although complexes involving cdk4 or cdk6 were readily observed in many of the cell lines, no complexes were detectable in human cell s harbouring, DNA tumour virus oncoproteins or in which the retinblast oma gene product (pRb) is mutated or missing. These data suggest that as well as being a potential substrate for D-cyclin-kinases, functiona l pRb contributes to the formation or stability of the complexes, at l east in human cells.