cyclin-dependent kinase inhibitors

(= CKIs)

Two classes of CKIs are known in mammals, the p21CIP1/Waf1 class that includes p27KIP1 and p57KIP2 and that inhibit all G1/S cyclin-dependent kinases (cdks), and the p16INK4 class that bind and inhibit only Cdk4 and Cdk6. The p21CIP1 inhibitor is transcriptionally regulated by p53 tumour suppressor, is important in G1 DNA-damage checkpoint, and its expression is associated with terminally differentiating tissues. Deletion of p21CIP1 is non-lethal in mice; deletion of p27KIP1 leads to relatively normal mice but with some proliferation disorders, deletion of p57KIP2 causes fairly major developmental abnormalities similar to Beckwith-Wiedemann syndrome. See also ICK1, Waf-1.