Cyclin-dependent kinases and pRb: regulators of the proliferation-differentiation switch.

The retinoblastoma susceptibility gene (RB1) is essential for normal embryonic development. Loss of RB1 leads to uncontrolled proliferation of a number of cell types but may also prevent proper terminal differentiation. The growth-suppressive and differentiation-inducing properties of pRb are impaired by cyclin-dependent kinase (cdk)-mediated phosphorylation. Hence, inhibition of cdk activity is probably a prerequisite for terminal differentiation. Indeed, forced cyclin or cdk expression can prevent terminal differentiation in various cell types, probably through inhibition of pRb and, possibly, differentiation-specific transcription factors.