Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) (Pin1)

Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) is a unique enzyme that specifically recognizes and isomerizes phosphorylated Serine/Threonine-Proline (pSer/Thr-Pro) motifs in target proteins [2, 3]. This conformational change acts as a post-phosphorylation molecular switch, regulating the function, stability, and subcellular localization of numerous proteins involved in the cell cycle and signal transduction [4, 8]. In oncology, Pin1 is frequently overexpressed and functions as a master regulator that simultaneously activates multiple oncogenic pathways, such as Cyclin D1, c-Myc, and beta-catenin, while inactivating tumor suppressors like p53 and PML [3, 17]. Conversely, its downregulation is associated with neurodegenerative conditions like Alzheimer's disease, where it normally prevents the formation of toxic tau conformations [13, 18]. Therapeutic strategies currently focus on small-molecule inhibitors and degraders, such as all-trans retinoic acid and arsenic trioxide, which have shown efficacy in degrading Pin1 and suppressing tumor growth in preclinical models [3, 24]. However, the dual role of Pin1 in cancer and neurodegeneration presents a significant therapeutic challenge, as long-term inhibition for cancer treatment could potentially increase the risk of neurological side effects [13, 16].

Other names

PPIase Pin1Rotamase Pin1Protein (peptidyl-prolyl cis/trans isomerase) NIMA-interacting 1DODUBL5

Inhibition of peptidyl-prolyl isomerase catalytic activity, induction of proteasome-dependent degradation, and covalent modification of the active site.