Publication Date:
1999-09-11
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Naidoo, N -- Song, W -- Hunter-Ensor, M -- Sehgal, A -- New York, N.Y. -- Science. 1999 Sep 10;285(5434):1737-41.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10481010" target="_blank"〉PubMed〈/a〉
Keywords:
Acetylcysteine/analogs & derivatives/pharmacology
;
Animals
;
*Biological Clocks
;
Cells, Cultured
;
*Circadian Rhythm
;
Cysteine Endopeptidases/*physiology
;
Cysteine Proteinase Inhibitors/pharmacology
;
Darkness
;
Drosophila
;
*Drosophila Proteins
;
Feedback
;
Insect Proteins/*metabolism
;
Leucine/analogs & derivatives/pharmacology
;
Leupeptins/pharmacology
;
*Light
;
Multienzyme Complexes/*physiology
;
Neurons/*metabolism
;
Phosphorylation
;
Phosphotyrosine/metabolism
;
Protease Inhibitors/pharmacology
;
Proteasome Endopeptidase Complex
;
Ubiquitins/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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