The prolyl isomerase Pin1 is a P53 binding protein [
105]. It participates in the cell cycle progression through regulation of cell cycle-related proteins such as CDK1, CDC25C, Wee1, Myt1, and PLK1, and regulates G2/M progression. Pin1 is a peptidyl-prolyl cis/trans isomerase, which specifically recognizes phosphorylated serine or threonine and proline, originally identified in a yeast two-hybrid screen [
106]. Pin1 is able to change the function of the protein it is interacting with [
107]. Pin1 participates in the regulation of cell cycle progression, apoptosis, control of key protein expression, proliferation, and oncogenic transformation in a phosphorylation-dependent manner [
108,
109]. Pin1 plays an important catalytic role in many cellular events by affecting the conformational changes of the pSer/Thr-Pro motif [
110]. Overexpression of Pin1 promotes tumor growth, while its inhibition leads to tumor cell apoptosis [
111,
112]. Pin1 plays an important role in tumorigenesis, and it has been found to be overexpressed in many cancers, including breast cancer [
113], hepatocellular carcinoma [
114], non-small cell lung cancer [
115], esophageal squamous cell carcinoma [
116], prostate cancer [
117], oral squamous cell carcinoma [
118], as an effective anticancer target [
119].
Studies have found that Pin1 plays an important role in regulating CDC25C phosphatase activity. Pin1 was originally thought to dephosphorylate CDC25C, negatively regulating its function and inhibiting the activation of the cyclin B1/CDK1 complex; however, subsequent studies have shown that Pin1 can also activate CDC25C. Since Pin1 contains a pSer/pThr binding site, a protein with a this motif is preferentially identified as an isomerization substrate. The five pSer/pThr-Pro sites in the mitotic form of
X. laevis CDC25C are potential Pin1 substrates. Pin1 catalyzes the conformational change of CDC25C and promotes its dephosphorylation by phosphoprotein phosphatase 2A (PP2A), which is considered to be a conformation-specific phosphatase. Pin1 promotes the removal of CDC25C phosphate by PP2A1 by catalyzing the isomerization of specific pSer/Thr-Pro motifs. Pin1 stably binds to CDC25C through pThr48-Pro and pThr67-Pro sites, promoting mitosis and microtubule assembly [
120,
121].
It is known that Wee1 protein kinase negatively regulates CDK1 activity by phosphorylating the Thr14 and Tyr15 residues of CDK1, while Pin1 binding to Wee1 can neutralize the inhibitory effect of Wee1 on CDK1 [
122], enhance the activity of cyclin B1/CDK1 complex, regulate G2/M progression, and promote Pin1 in cell cycle control and cancer.