A Role for the Proteasome in the Light Response of the Timeless Clock Protein

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Science  10 Sep 1999:
Vol. 285, Issue 5434, pp. 1737-1741
DOI: 10.1126/science.285.5434.1737

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The cyclic expression of the period (PER) and timeless (TIM) proteins is critical for the molecular circadian feedback loop inDrosophila. 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.

  • * Present address: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

  • To whom correspondence should be addressed. E-mail: amita{at}

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