Prolyl isomerase Pin1 regulates the osteogenic activity of Osterix

Mol Cell Endocrinol. 2015 Jan 15:400:32-40. doi: 10.1016/j.mce.2014.11.017. Epub 2014 Nov 24.

Abstract

Osterix is an essential transcription factor for osteoblast differentiation and bone formation. The mechanism of regulation of Osterix by post-translational modification remains unknown. Peptidyl-prolyl isomerase 1 (Pin1) catalyzes the isomerization of pSer/Thr-Pro bonds and induces a conformational change in its substrates, subsequently regulating diverse cellular processes. In this study, we demonstrated that Pin1 interacts with Osterix and influences its protein stability and transcriptional activity. This regulation is likely due to the suppression of poly-ubiquitination-mediated proteasomal degradation of Osterix. Collectively, our data demonstrate that Pin1 is a novel regulator of Osterix and may play an essential role in the regulation of osteogenic differentiation.

Keywords: Osteoblast differentiation; Osterix; Pin1.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Line
  • Fibroblasts / cytology
  • Fibroblasts / metabolism*
  • Gene Expression Regulation
  • Genes, Reporter
  • HEK293 Cells
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • Mice
  • Myoblasts / cytology
  • Myoblasts / metabolism*
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Osteoblasts / cytology
  • Osteoblasts / metabolism*
  • Osteogenesis / genetics*
  • Peptidylprolyl Isomerase / genetics
  • Peptidylprolyl Isomerase / metabolism*
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Stability
  • Proteolysis
  • Signal Transduction
  • Sp7 Transcription Factor
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic

Substances

  • NIMA-Interacting Peptidylprolyl Isomerase
  • Sp7 Transcription Factor
  • Sp7 protein, mouse
  • Transcription Factors
  • Luciferases
  • Proteasome Endopeptidase Complex
  • PIN1 protein, human
  • Peptidylprolyl Isomerase
  • Pin1 protein, mouse