|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
6916
|
|
pubmed:dateCreated |
2002-12-12
|
|
pubmed:abstractText |
Protein phosphorylation has a key role in modulating the stabilities of circadian clock proteins in a manner specific to the time of day. A conserved feature of animal clocks is that Period (Per) proteins undergo daily rhythms in phosphorylation and levels, events that are crucial for normal clock progression. Casein kinase Iepsilon (CKIepsilon) has a prominent role in regulating the phosphorylation and abundance of Per proteins in animals. This was first shown in Drosophila with the characterization of Doubletime (Dbt), a homologue of vertebrate casein kinase Iepsilon. However, it is not clear how Dbt regulates the levels of Per. Here we show, using a cell culture system, that Dbt promotes the progressive phosphorylation of Per, leading to the rapid degradation of hyperphosphorylated isoforms by the ubiquitin-proteasome pathway. Slimb, an F-box/WD40-repeat protein functioning in the ubiquitin-proteasome pathway interacts preferentially with phosphorylated Per and stimulates its degradation. Overexpression of slimb or expression in clock cells of a dominant-negative version of slimb disrupts normal rhythmic activity in flies. Our findings suggest that hyperphosphorylated Per is targeted to the proteasome by interactions with Slimb.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Casein Kinase Iepsilon,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Drosophila Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Insect Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PER protein, Drosophila,
http://linkedlifedata.com/resource/pubmed/chemical/Period Circadian Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/dco protein, Drosophila,
http://linkedlifedata.com/resource/pubmed/chemical/supernumerary limbs protein...,
http://linkedlifedata.com/resource/pubmed/chemical/timeless protein, Drosophila
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Dec
|
|
pubmed:issn |
0028-0836
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
12
|
|
pubmed:volume |
420
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
673-8
|
|
pubmed:dateRevised |
2009-11-19
|
|
pubmed:meshHeading |
pubmed-meshheading:12442174-Animals,
pubmed-meshheading:12442174-Animals, Genetically Modified,
pubmed-meshheading:12442174-Biological Clocks,
pubmed-meshheading:12442174-Casein Kinase Iepsilon,
pubmed-meshheading:12442174-Cell Cycle Proteins,
pubmed-meshheading:12442174-Cell Line,
pubmed-meshheading:12442174-Circadian Rhythm,
pubmed-meshheading:12442174-Cysteine Endopeptidases,
pubmed-meshheading:12442174-Drosophila Proteins,
pubmed-meshheading:12442174-Drosophila melanogaster,
pubmed-meshheading:12442174-Insect Proteins,
pubmed-meshheading:12442174-Motor Activity,
pubmed-meshheading:12442174-Multienzyme Complexes,
pubmed-meshheading:12442174-Mutation,
pubmed-meshheading:12442174-Nuclear Proteins,
pubmed-meshheading:12442174-Period Circadian Proteins,
pubmed-meshheading:12442174-Phosphorylation,
pubmed-meshheading:12442174-Proteasome Endopeptidase Complex,
pubmed-meshheading:12442174-Protein Binding,
pubmed-meshheading:12442174-Protein Isoforms,
pubmed-meshheading:12442174-Protein Kinases,
pubmed-meshheading:12442174-RNA Interference,
pubmed-meshheading:12442174-Substrate Specificity,
pubmed-meshheading:12442174-Ubiquitin-Protein Ligases
|
|
pubmed:year |
2002
|
|
pubmed:articleTitle |
Role for Slimb in the degradation of Drosophila Period protein phosphorylated by Doubletime.
|
|
pubmed:affiliation |
Graduate Program in Physiology and Neurobiology, Rutgers University, Center for Advanced Biotechnology and Medicine, 679 Hoes Lane, Piscataway, New Jersey 08854, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|
