Regulation of G₁ cyclin-dependent kinases in liver regeneration

The liver serves as a suitable model for studying tissue regeneration. Although various growth factors have been implicated in the promotion of this process, their precise role in liver regeneration remains to be elucidated. Whatever the extracellular signals may be, they all converge on cell cycle regulators in the nucleus, where the sequential activation of cyclin-dependent kinases (Cdk) takes place. The activities of Cdk are regulated positively through their association with cognate cyclins, and negatively via interactions with Cdk inhibitors. In this review article, our recent data as well as results of previous reports on how these cell cycle regulators trigger and/or terminate the process of liver regeneration are summarized. The authors believe that 'knockout' mice, in which specific genes are deleted, will be useful for providing further insight into the positive and negative regulation of liver regeneration.