Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2004-2-9
pubmed:abstractText
The ubiquitin-proteasome system is responsible for the regulation and turnover of the nuclear transcription factor MyoD. The degradation of MyoD can occur via an NH2 terminus-dependent pathway or a lysine-dependent pathway, suggesting that MyoD ubiquitination may be driven by different mechanisms. To understand this process, deletion analysis was used to identify the region of MyoD that is required for rapid proteolysis in the lysine-dependent pathway. Here we report that the basic helix-loop-helix domain is required for ubiquitination and lysine-dependent degradation of MyoD in the nucleus. Site-directed mutagenesis in MyoD revealed that lysine 133 is the major internal lysine of ubiquitination. The half-life of the MyoD K133R mutant protein was longer than that of wild type MyoD, substantiating the implication of lysine 133 in the turnover of MyoD in myoblasts. In addition, the MyoD K133R mutant displayed activity 2-3-fold higher than the wild type in transactivation muscle-specific gene and myogenic conversion of 10T1/2 cells. Taken together, our data demonstrate that lysine 133 is targeted for ubiquitination and rapid degradation of MyoD in the lysine-dependent pathway and plays an integral role in compromising MyoD activity in the nucleus.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
13
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5413-20
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:14660660-Amino Acid Sequence, pubmed-meshheading:14660660-Animals, pubmed-meshheading:14660660-Blotting, Western, pubmed-meshheading:14660660-Cell Line, pubmed-meshheading:14660660-Cell Nucleus, pubmed-meshheading:14660660-Cycloheximide, pubmed-meshheading:14660660-DNA, pubmed-meshheading:14660660-DNA, Complementary, pubmed-meshheading:14660660-Enzyme Inhibitors, pubmed-meshheading:14660660-Gene Deletion, pubmed-meshheading:14660660-Genetic Vectors, pubmed-meshheading:14660660-Luciferases, pubmed-meshheading:14660660-Lysine, pubmed-meshheading:14660660-Mice, pubmed-meshheading:14660660-Molecular Sequence Data, pubmed-meshheading:14660660-Mutagenesis, Site-Directed, pubmed-meshheading:14660660-Mutation, pubmed-meshheading:14660660-MyoD Protein, pubmed-meshheading:14660660-Plasmids, pubmed-meshheading:14660660-Precipitin Tests, pubmed-meshheading:14660660-Protein Structure, Tertiary, pubmed-meshheading:14660660-Protein Synthesis Inhibitors, pubmed-meshheading:14660660-Time Factors, pubmed-meshheading:14660660-Transcriptional Activation, pubmed-meshheading:14660660-Transfection, pubmed-meshheading:14660660-Ubiquitin
pubmed:year
2004
pubmed:articleTitle
Critical role for lysine 133 in the nuclear ubiquitin-mediated degradation of MyoD.
pubmed:affiliation
Laboratoire de Génétique Oncologique, UMR 8125 CNRS, 94805 Villejuif, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't