Figure 6.

Cyclin-dependent kinase (CDK) inhibitor proteins regulate cell cycle progression, growth arrest, and postmitotic neuronal migration. (A) Molecular mechanisms for G1/S transition. The transition from G1 to S phase is dependent on CyclinD-Cdk4/6 and CyclinE-Cdk2 activities, which phosphorylate Rb protein. The phosphorylated Rb protein dissociates E2F family transcription factors. Both E2F1 and E2F3 promote G1/S transition in neural progenitors, whereas E2F3, but not E2F1, regulates neuronal positioning. The activities of Cyclin-CDK complexes are suppressed by CDK inhibitor proteins, which are composed of a Cip/Kip family (p21^cip1, p27^kip1, and p57^kip2) and Ink4 family (p16^Ink4a, p15^Ink4b, p18^Ink4c, and p19^Ink4d). (B) Roles of CDK inhibitor proteins, p27^kip1 and p57^kip2, in cell cycle exit and subsequent neuronal migration. p57^kip2 and p27^kip1 preferentially control the cell cycle exit of neural progenitors for early-born (deep layer) and late-born (upper layer) neurons, respectively. p27^kip1 mainly functions in basal progenitors (orange cells) rather than apical progenitors (green cells). Both p27^kip1 and p57^kip2 have been shown to regulate the migration of postmitotic neurons as well as the cell cycle exit.