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.
Kranenburg
O
O
Department of Molecular Carcinogenesis, Sylvius Laboratory, Leiden University, The Netherlands.
van der Eb
A J
AJ
Zantema
A
A
D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D016193:G1 Phase; D016160:Retinoblastoma Protein / Q000502:physiology*
D016160:Retinoblastoma Protein; D018844:Cyclin-Dependent Kinases