Abstract
Cellular choices are determined by developmental and environmental stimuli through integrated signal transduction pathways. These critically depend on attainment of proper activation levels that in turn rely on post-translational modifications (PTMs) of single pathway members. Among these PTMs, post-phosphorylation prolyl-isomerization mediated by PIN1 represents a unique mechanism of spatial, temporal and quantitative control of signal transduction. Indeed PIN1 was shown to be crucial for determining activation levels of several pathways and biological outcomes downstream to a plethora of stimuli. Of note, studies performed in different model organisms and humans have shown that hormonal, nutrient, and oncogenic stimuli simultaneously affect both PIN1 activity and the pathways that depend on PIN1-mediated prolyl-isomerization, suggesting the existence of evolutionarily conserved molecular circuitries centered on this isomerase. This review focuses on molecular mechanisms and cellular processes like proliferation, metabolism, and stem cell fate, that are regulated by PIN1 in physiological conditions, discussing how these are subverted in and hijacked by cancer cells. Current status and open questions regarding the use of PIN1 as biomarker and target for cancer therapy as well as clinical development of PIN1 inhibitors are also addressed.
Highlights
Cells respond to a continuous flow of intra- and extra-cellular stimuli through integrated signal transduction pathways
TP53 missense mutations that confer neomorphic oncogenic activities [117] are very frequent in human cancers and we have shown that PIN1 supports the oncogenic activities of these mutant p53 proteins in breast [16] and hepatocellular carcinomas [118]
Regulation of the phosphorylation and transcriptional landscapes by PIN1 establishes this enzyme as a central effector of dynamic molecular switches imposed by environmental and cell-intrinsic cues
Summary
Cells respond to a continuous flow of intra- and extra-cellular stimuli through integrated signal transduction pathways. We will describe the biochemical consequences of the structural modifications exerted by PIN1 on several proteins and their impact on global functions in signal transduction and cellular processes in different animal and human models.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
