Dual Roles of Pin1 in Cancer Development and Progression

Abstract

Pin1 is a unique peptidyl-prolyl cis/trans isomerase (PPIase) that catalyzes the cis/trans isomerization of peptidyl-prolyl peptide bonds of its substrate proteins by binding to their specific phosphorylated Ser/Thr-Pro (pSer/Thr-Pro) motifs. This alters the conformation of target proteins and consequently affects their stability, intracellular localization, and/or biological functions. The abnormal overexpression of Pin1 is observed in some malignancies, which is associated with cancer cell proliferation, migration and invasion. However, a role for Pin1 as a putative tumor suppressor has recently been suggested. Systematic dissection of pro-oncogenic vs. tumor suppressive functions of Pin1 will be necessary.

Keywords: PPIase; Pin1; pSer/Thr-Pro motif; phosphorylation-dependent peptidyl-prolyl isomerase; proline isomerization; proline-directed protein kinases.