Drosophila peptidyl-prolyl isomerase Pin1 modulates circadian rhythms via regulating levels of PERIOD

Biochem Biophys Res Commun. 2015 Jul 31;463(3):235-40. doi: 10.1016/j.bbrc.2015.05.033. Epub 2015 May 18.

Abstract

In animal circadian clock machinery, the phosphorylation program of PERIOD (PER) leads to the spatio-temporal regulation of diverse PER functions, which are crucial for the maintenance of ~24-hr circadian rhythmicity. The peptidyl-prolyl isomerase PIN1 modulates the diverse functions of its substrates by inducing conformational changes upon recognizing specific phosphorylated residues. Here, we show that overexpression of Drosophila pin1, dodo (dod), lengthens the locomotor behavioral period. Using Drosophila S2 cells, we demonstrate that Dod associates preferentially with phosphorylated species of PER, which delays the phosphorylation-dependent degradation of PER. Consistent with this, PER protein levels are higher in flies overexpressing dod. Taken together, we suggest that Dod plays a role in the maintenance of circadian period by regulating PER metabolism.

Keywords: Circadian rhythms; Dodo; Drosophila; PERIOD; Peptidyl-prolyl isomerase; Pin1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Circadian Rhythm*
  • Drosophila / genetics
  • Drosophila / physiology*
  • Drosophila Proteins / metabolism*
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Peptidylprolyl Isomerase / genetics
  • Peptidylprolyl Isomerase / metabolism*
  • Period Circadian Proteins / metabolism*
  • Phosphorylation
  • Protein Binding
  • Protein Interaction Maps
  • Proteolysis
  • Up-Regulation

Substances

  • Drosophila Proteins
  • NIMA-Interacting Peptidylprolyl Isomerase
  • PER protein, Drosophila
  • Period Circadian Proteins
  • Peptidylprolyl Isomerase
  • dod protein, Drosophila