The Drosophila CLOCK protein undergoes daily rhythms in abundance, phosphorylation, and interactions with the PER-TIM complex

Neuron. 1998 Oct;21(4):857-67. doi: 10.1016/s0896-6273(00)80601-7.


We report the in vivo characterization of the Drosophila CLOCK protein (dCLOCK), a transcription factor that is required for the expression of the circadian clock genes period (per) and timeless (tim). dCLOCK undergoes circadian fluctuations in abundance, is phosphorylated throughout a daily cycle, and interacts with PER, TIM, and/or the PER-TIM complex during the night but not during most of the day. Our results suggest that PER and TIM participate in transcriptional autoinhibition by physically interacting with dCLOCK or a dCLOCK-containing complex. Nevertheless, in the absence of PER or TIM, the levels of dCLOCK are constitutively low, indicating that PER and TIM also act as positive elements in the feedback loop by stimulating the production of dCLOCK.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CLOCK Proteins
  • Circadian Rhythm* / physiology
  • Drosophila
  • Drosophila Proteins*
  • Drug Interactions
  • Insect Proteins / physiology*
  • Nuclear Proteins / physiology*
  • Period Circadian Proteins
  • Phosphorylation
  • Trans-Activators / metabolism*


  • Drosophila Proteins
  • Insect Proteins
  • Nuclear Proteins
  • PER protein, Drosophila
  • Period Circadian Proteins
  • Trans-Activators
  • tim protein, Drosophila
  • CLOCK Proteins