Prolyl isomerase Pin1 as a molecular switch to determine the fate of phosphoproteins

Trends Biochem Sci. 2011 Oct;36(10):501-14. doi: 10.1016/j.tibs.2011.07.001. Epub 2011 Aug 17.

Abstract

Pin1 is a highly conserved enzyme that only isomerizes specific phosphorylated Ser/Thr-Pro bonds in certain proteins, thereby inducing conformational changes. Such conformational changes represent a novel and tightly controlled signaling mechanism regulating a spectrum of protein activities in physiology and disease; often through phosphorylation-dependent, ubiquitin-mediated proteasomal degradation. In this review, we summarize recent advances in elucidating the role and regulation of Pin1 in controlling protein stability. We also propose a mechanism by which Pin1 functions as a molecular switch to control the fates of phosphoproteins. We finally stress the need to develop tools to visualize directly Pin1-catalyzed protein conformational changes as a way to determine their roles in the development and treatment of human diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging
  • Gene Expression
  • Humans
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Neoplasms / metabolism
  • Neurodegenerative Diseases / metabolism
  • Peptidylprolyl Isomerase / genetics
  • Peptidylprolyl Isomerase / metabolism*
  • Phosphoproteins / chemistry
  • Phosphoproteins / metabolism*
  • Protein Conformation
  • Protein Stability
  • Proteolysis
  • Telomere / metabolism

Substances

  • NIMA-Interacting Peptidylprolyl Isomerase
  • Phosphoproteins
  • PIN1 protein, human
  • Peptidylprolyl Isomerase

Grants and funding