Cip/Kip cell-cycle inhibitors: A neuro-oncological perspective

The cell cycle is a precisely controlled cellular program that ensures norm al cellular proliferation and development. The cyclin-dependant kinases (CD K) are molecules central to the continued progression through the cell-cycl e checkpoints and as such are regulated by various mechanisms including cyc lin levels, phosphorylation/dephosphorylation and cyclin-dependant kinase i nhibitors (CKI). The CKIs are grouped into two families based on their stru cture and function, four Ink4 CKIs and three Cip/Kip CKIs. Abnormalities in these proteins can give rise to developmental defects and cancer. In this review, we will discuss the biochemistry and cell biology of the each of th e Cip/Kip CKIs, their role in development as evidenced by targeted mutation s in mice, and their role as possible tumor suppressor genes.