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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2007-12-6
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pubmed:abstractText |
Muscle atrophy occurs in many pathological states and results primarily from accelerated protein degradation and activation of the ubiquitin-proteasome pathway. However, the importance of lysosomes in muscle atrophy has received little attention. Activation of FoxO transcription factors is essential for the atrophy induced by denervation or fasting, and activated FoxO3 by itself causes marked atrophy of muscles and myotubes. Here, we report that FoxO3 does so by stimulating overall protein degradation and coordinately activating both lysosomal and proteasomal pathways. Surprisingly, in C2C12 myotubes, most of this increased proteolysis is mediated by lysosomes. Activated FoxO3 stimulates lysosomal proteolysis in muscle (and other cell types) by activating autophagy. FoxO3 also induces the expression of many autophagy-related genes, which are induced similarly in mouse muscles atrophying due to denervation or fasting. These studies indicate that decreased IGF-1-PI3K-Akt signaling activates autophagy not only through mTOR but also more slowly by a transcription-dependent mechanism involving FoxO3.
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pubmed:grant |
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pubmed:commentsCorrections |
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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/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Fbxo32 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Forkhead Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/FoxO3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Muscle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/SKP Cullin F-Box Protein Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1550-4131
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
6
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
472-83
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pubmed:dateRevised |
2010-12-3
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pubmed:meshHeading |
pubmed-meshheading:18054316-Animals,
pubmed-meshheading:18054316-Autophagy,
pubmed-meshheading:18054316-Base Sequence,
pubmed-meshheading:18054316-Cell Line,
pubmed-meshheading:18054316-DNA,
pubmed-meshheading:18054316-Forkhead Transcription Factors,
pubmed-meshheading:18054316-Gene Expression Regulation,
pubmed-meshheading:18054316-Lysosomes,
pubmed-meshheading:18054316-Mice,
pubmed-meshheading:18054316-Mice, Knockout,
pubmed-meshheading:18054316-Models, Biological,
pubmed-meshheading:18054316-Muscle Fibers, Skeletal,
pubmed-meshheading:18054316-Muscle Proteins,
pubmed-meshheading:18054316-Muscular Atrophy,
pubmed-meshheading:18054316-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:18054316-Proteasome Endopeptidase Complex,
pubmed-meshheading:18054316-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:18054316-SKP Cullin F-Box Protein Ligases,
pubmed-meshheading:18054316-Ubiquitin-Protein Ligases
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pubmed:year |
2007
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pubmed:articleTitle |
FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells.
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pubmed:affiliation |
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, 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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