Fig. 1.

The p27 IDR integrates proliferative signals from NRTKs to release active Cdk2/cyclin A via T187 phosphorylation. Proliferative signals activate NRTKs that phosphorylate p27 at Y88, partially restoring Cdk2 activity (step 1). This allows for intracomplex phosphorylation of p27 at T187 by Cdk2 and creates a phosphodegron (step 2). Recruitment of the SCF^Skp2 E3 ubiquitin ligase leads to ubiquitination of lysine residues within p27-C (step 3) followed by selective degradation of p27 by the proteasome (step 4) and release of the fully active Cdk2/cyclin A. The primary sequence of the p27 IDR is shown with positively and negatively charged residues depicted in blue and red, respectively. The primary substrate motif is highlighted in yellow.