rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5826
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pubmed:dateCreated |
2007-5-14
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pubmed:abstractText |
One component of the circadian clock in mammals is the Clock-Bmal1 heterodimeric transcription factor. Among its downstream targets, two genes, Cry1 and Cry2, encode inhibitors of the Clock-Bmal1 complex that establish a negative-feedback loop. We found that both Cry1 and Cry2 proteins are ubiquitinated and degraded via the SCF(Fbxl3) ubiquitin ligase complex. This regulation by SCF(Fbxl3) is a prerequisite for the efficient and timely reactivation of Clock-Bmal1 and the consequent expression of Per1 and Per2, two regulators of the circadian clock that display tumor suppressor activity. Silencing of Fbxl3 produced no effect in Cry1-/-;Cry2-/- cells, which shows that Fbxl3 controls clock oscillations by mediating the degradation of CRY proteins.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ARNTL Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/ARNTL protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Arntl protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Basic Helix-Loop-Helix...,
http://linkedlifedata.com/resource/pubmed/chemical/CLOCK Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/CLOCK protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CRY1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CRY2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Clock protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cry1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cry2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cryptochromes,
http://linkedlifedata.com/resource/pubmed/chemical/F-Box Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Flavoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PER1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Per1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Per2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Period Circadian Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SKP Cullin F-Box Protein Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1095-9203
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
11
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pubmed:volume |
316
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
900-4
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17463251-ARNTL Transcription Factors,
pubmed-meshheading:17463251-Animals,
pubmed-meshheading:17463251-Basic Helix-Loop-Helix Transcription Factors,
pubmed-meshheading:17463251-CLOCK Proteins,
pubmed-meshheading:17463251-Cell Cycle Proteins,
pubmed-meshheading:17463251-Cells, Cultured,
pubmed-meshheading:17463251-Circadian Rhythm,
pubmed-meshheading:17463251-Cryptochromes,
pubmed-meshheading:17463251-F-Box Proteins,
pubmed-meshheading:17463251-Flavoproteins,
pubmed-meshheading:17463251-HeLa Cells,
pubmed-meshheading:17463251-Humans,
pubmed-meshheading:17463251-Mice,
pubmed-meshheading:17463251-NIH 3T3 Cells,
pubmed-meshheading:17463251-Nuclear Proteins,
pubmed-meshheading:17463251-Period Circadian Proteins,
pubmed-meshheading:17463251-Promoter Regions, Genetic,
pubmed-meshheading:17463251-RNA Interference,
pubmed-meshheading:17463251-SKP Cullin F-Box Protein Ligases,
pubmed-meshheading:17463251-Trans-Activators,
pubmed-meshheading:17463251-Transcription Factors,
pubmed-meshheading:17463251-Transfection,
pubmed-meshheading:17463251-Ubiquitin
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pubmed:year |
2007
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pubmed:articleTitle |
SCFFbxl3 controls the oscillation of the circadian clock by directing the degradation of cryptochrome proteins.
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pubmed:affiliation |
Department of Pathology, NYU Cancer Institute, New York University School of Medicine, 550 First Avenue, MSB 599, New York, NY 10016, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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