RRC ID 15548
著者 Lamaze A, Lamouroux A, Vias C, Hung HC, Weber F, Rouyer F.
タイトル The E3 ubiquitin ligase CTRIP controls CLOCK levels and PERIOD oscillations in Drosophila.
ジャーナル EMBO Rep
Abstract In the Drosophila circadian clock, the CLOCK/CYCLE complex activates the period and timeless genes that negatively feedback on CLOCK/CYCLE activity. The 24-h pace of this cycle depends on the stability of the clock proteins. RING-domain E3 ubiquitin ligases have been shown to destabilize PERIOD or TIMELESS. Here we identify a clock function for the circadian trip (ctrip) gene, which encodes a HECT-domain E3 ubiquitin ligase. ctrip expression in the brain is mostly restricted to clock neurons and its downregulation leads to long-period activity rhythms in constant darkness. This altered behaviour is associated with high CLOCK levels and persistence of phosphorylated PERIOD during the subjective day. The control of CLOCK protein levels does not require PERIOD. Thus, CTRIP seems to regulate the pace of the oscillator by controlling the stability of both the activator and the repressor of the feedback loop.
巻・号 12(6)
ページ 549-57
公開日 2011-6-1
DOI 10.1038/embor.2011.64
PII embor201164
PMID 21525955
PMC PMC3128276
MeSH Amino Acid Sequence Animals Base Sequence Biological Clocks / genetics Brain / metabolism CLOCK Proteins / metabolism* Down-Regulation Drosophila / enzymology* Drosophila / metabolism Drosophila Proteins / metabolism* Female Gene Expression Regulation* Gene Order Male Molecular Sequence Data Motor Activity / physiology Neurons / metabolism Period Circadian Proteins / metabolism* Protein Stability RNA Interference Ubiquitin-Protein Ligases / antagonists & inhibitors Ubiquitin-Protein Ligases / genetics Ubiquitin-Protein Ligases / metabolism*
IF 7.497
引用数 18
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
ショウジョウバエ 14656R-3 17735R-3