FIGURE 2.

PIN1-mediated positive feedback loop for progression of G1 checkpoint. During G1 phase, PIN1 increases the binding of retinoblastoma protein (Rb) with cyclin D1-CDK4/6, resulting in inactivation of Rb and the release of E2F for the activation of PIN1 expression. Through PIN1-mediated isomerization, PIN1 enhances cyclin D1 expression by increasing the transcriptional activities of β-catenin, nuclear factor kappa B (NF-κB) and c-Jun. In addition, PIN1 also binds and increases the protein stability of cyclin D1, which in turn enhances its protein level. As a result, cyclin D1 binds and activates CDK4/6, leading to further inactivation of Rb for E2F dissociation.