Differentiation-related changes in the cell cycle traverse.

This review examines recent developments relating to the interface between cell proliferation and differentiation. It is suggested that the mechanism responsible for this transition is more akin to a "dimmer" than to a "switch," that it is more useful to refer to early and late stages of differentiation rather than to "terminal" differentiation, and examples of the reversibility of differentiation are provided. An outline of the established paradigm of cell cycle regulation is followed by summaries of recent studies that suggest that this paradigm is overly simplified and should be interpreted in the context of different cell types. The role of inhibitors of cyclin-dependent kinases in differentiation is discussed, but the data are still inconclusive. An increasing interest in the changes in G2/M transition during differentiation is illustrated by examples of polyploidization during differentiation, such as megakaryocyte maturation. Although the retinoblastoma protein is currently maintaining its prominent role in control of proliferation and differentiation, it is anticipated that equally important regulators will be discovered and provide an explanation at the molecular level for the gradual transition from proliferation to differentiation.