A role for the proteasome in the light response of the timeless clock protein Academic Article uri icon


MeSH Major

  • Biological Clocks
  • Circadian Rhythm
  • Cysteine Endopeptidases
  • Drosophila Proteins
  • Insect Proteins
  • Light
  • Multienzyme Complexes
  • Neurons


  • The cyclic expression of the period (PER) and timeless (TIM) proteins is critical for the molecular circadian feedback loop in Drosophila. The entrainment by light of the circadian clock is mediated by a reduction in TIM levels. To elucidate the mechanism of this process, the sensitivity of TIM regulation by light was tested in an in vitro assay with inhibitors of candidate proteolytic pathways. The data suggested that TIM is degraded through a ubiquitin-proteasome mechanism. In addition, in cultures from third-instar larvae, TIM degradation was blocked specifically by inhibitors of proteasome activity. Degradation appeared to be preceded by tyrosine phosphorylation. Finally, TIM was ubiquitinated in response to light in cultured cells.

publication date

  • September 10, 1999



  • Academic Article



  • eng

Digital Object Identifier (DOI)

  • 10.1126/science.285.5434.1737

PubMed ID

  • 10481010

Additional Document Info

start page

  • 1737

end page

  • 41


  • 285


  • 5434