Source:http://linkedlifedata.com/resource/pubmed/id/19073596
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
|
pubmed:dateCreated |
2009-2-9
|
pubmed:abstractText |
We recently presented evidence that the subunit eIF3-f of the eukaryotic initiation translation factor eIF3 that interacts with the E3-ligase Atrogin-1/muscle atrophy F-box (MAFbx) for polyubiquitination and proteasome-mediated degradation is a key target that accounts for MAFbx function during muscle atrophy. To understand this process, deletion analysis was used to identify the region of eIF3-f that is required for its proteolysis. Here, we report that the highly conserved C-terminal domain of eIF3-f is implicated for MAFbx-directed polyubiquitination and proteasomal degradation. Site-directed mutagenesis of eIF3-f revealed that the six lysine residues within this domain are required for full polyubiquitination and degradation by the proteasome. In addition, mutation of these six lysines (mutant K(5-10)R) displayed hypertrophic activity in cellulo and in vivo and was able to protect against starvation-induced muscle atrophy. Taken together, our data demonstrate that the C-terminal modifications, believed to be critical for proper eIF3-f regulation, are essential and contribute to a fine-tuning mechanism that plays an important role for eIF3-f function in skeletal muscle.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Eukaryotic Initiation Factor-3,
http://linkedlifedata.com/resource/pubmed/chemical/Fbxo32 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Lysine,
http://linkedlifedata.com/resource/pubmed/chemical/Muscle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/SKP Cullin F-Box Protein Ligases
|
pubmed:status |
MEDLINE
|
pubmed:month |
Feb
|
pubmed:issn |
0021-9258
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
13
|
pubmed:volume |
284
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
4413-21
|
pubmed:meshHeading |
pubmed-meshheading:19073596-Animals,
pubmed-meshheading:19073596-Cell Line,
pubmed-meshheading:19073596-Eukaryotic Initiation Factor-3,
pubmed-meshheading:19073596-Lysine,
pubmed-meshheading:19073596-Mice,
pubmed-meshheading:19073596-Muscle, Skeletal,
pubmed-meshheading:19073596-Muscle Proteins,
pubmed-meshheading:19073596-Muscular Atrophy,
pubmed-meshheading:19073596-Mutagenesis, Site-Directed,
pubmed-meshheading:19073596-Proteasome Endopeptidase Complex,
pubmed-meshheading:19073596-Protein Structure, Tertiary,
pubmed-meshheading:19073596-SKP Cullin F-Box Protein Ligases,
pubmed-meshheading:19073596-Starvation,
pubmed-meshheading:19073596-Ubiquitination
|
pubmed:year |
2009
|
pubmed:articleTitle |
MAFbx/Atrogin-1 controls the activity of the initiation factor eIF3-f in skeletal muscle atrophy by targeting multiple C-terminal lysines.
|
pubmed:affiliation |
Université de Montpellier-Sud de France.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|