Cell cycle progression is regulated by a series of cyclin-dependent kinases consisting of catalytic subunits, designated Cdks, as well as activating subunits, designated cyclins. Orderly progression through the cell cycle requires the activation and inactivation of different cyclin-Cdks at appropriate times. A series of proteins has recently been described that function as "mitotic inhibitors." These include p21, the levels of which are elevated upon DNA damage in G1 in a p53-dependent manner; p16; and a more recently described p16-related inhibitor designated p15. A p21-related protein, p27, has been described as a negative regulator of G1 progression and speculated to function as a possible mediator of TGFβ-induced G1 arrest. p27 interacts strongly with D-type cyclins and Cdk4 in vitro and, to a lesser extent, with cyclin E and Cdk2.
