Mammalian Cdk inhibitor proteins (CKIs) can be grouped into two families based on their structural and functional differences. The Cip/Kip family proteins (e.g. p21) have a broad binding specificity. These proteins bind preferentially to already formed cyclin-Cdk complexes and thus enhance complex formation. However, they inhibit the kinase activity of most complexes (e.g. S-Cdks), except in the case of G?-Cdk complexes where no inhibition occurs. Consequently, Cip/Kip family proteins have an overall positive effect on Cdk4/6 activity due to their help in bringing the subunits together. In contrast, the inhibitors of the INK4 family (e.g. p16) bind only to the Cdk subunit of G?-Cdks and prevent binding of both the G? cyclins and the Cip/Kip family CKIs. Based solely on these findings, would you expect p16 to activate (A) or inactivate (I) the S-Cdks in the presence of limited amounts of p21?

Question

Quizplus · Accepted Answer

In the absence of p16, p21 is sequestered by the G?-Cdk complex. Active p16, however, prevents p21 from binding, making it available to inhibit the S-Cdk complexes.

Mammalian Cdk Inhibitor Proteins (CKIs) Can Be Grouped into Two