Targeted degradation of TOC1 by ZTL modulates circadian function in Arabidopsis thaliana

Nature. 2003 Dec 4;426(6966):567-70. doi: 10.1038/nature02163.


The underlying mechanism of circadian rhythmicity appears to be conserved among organisms, and is based on negative transcriptional feedback loops forming a cellular oscillator (or 'clock'). Circadian changes in protein stability, phosphorylation and subcellular localization also contribute to the generation and maintenance of this clock. In plants, several genes have been shown to be closely associated with the circadian system. However, the molecular mechanisms proposed to regulate the plant clock are mostly based on regulation at the transcriptional level. Here we provide genetic and molecular evidence for a role of ZEITLUPE (ZTL) in the targeted degradation of TIMING OF CAB EXPRESSION 1 (TOC1) in Arabidopsis thaliana (thale cress). The physical interaction of TOC1 with ZTL is abolished by the ztl-1 mutation, resulting in constitutive levels of TOC1 protein expression. The dark-dependent degradation of TOC1 protein requires functional ZTL, and is prevented by inhibiting the proteosome pathway. Our results show that the TOC1-ZTL interaction is important in the control of TOC1 protein stability, and is probably responsible for the regulation of circadian period by the clock.

Publication types

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

MeSH terms

  • Arabidopsis / genetics
  • Arabidopsis / metabolism*
  • Arabidopsis Proteins / genetics
  • Arabidopsis Proteins / metabolism*
  • Biological Clocks
  • Circadian Rhythm / physiology*
  • Cysteine Endopeptidases / metabolism
  • Darkness
  • Gene Expression Regulation, Plant
  • Multienzyme Complexes / antagonists & inhibitors
  • Multienzyme Complexes / metabolism
  • Proteasome Endopeptidase Complex
  • Protein Binding
  • Protein Processing, Post-Translational*
  • RNA, Plant / genetics
  • RNA, Plant / metabolism
  • Substrate Specificity
  • Transcription Factors


  • Arabidopsis Proteins
  • Multienzyme Complexes
  • RNA, Plant
  • TOC1 protein, Arabidopsis
  • Transcription Factors
  • ZTL protein, Arabidopsis
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex