Cell cycle progression is regulated by a series of cyclin-dependent kinases that consist of catalytic subunits, designated Cdks, and 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 been recently 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 has been 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.