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

Abstract
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.