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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2008-2-14
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pubmed:abstractText |
Lafora progressive myoclonus epilepsy (LD) is a fatal autosomal recessive neurodegenerative disorder characterized by the presence of glycogen-like intracellular inclusions called Lafora bodies. LD is caused by mutations in two genes, EPM2A and EPM2B, encoding respectively laforin, a dual-specificity protein phosphatase, and malin, an E3 ubiquitin ligase. Previously, we and others have suggested that the interactions between laforin and PTG (a regulatory subunit of type 1 protein phosphatase) and between laforin and malin are critical in the pathogenesis of LD. Here, we show that the laforin-malin complex downregulates PTG-induced glycogen synthesis in FTO2B hepatoma cells through a mechanism involving ubiquitination and degradation of PTG. Furthermore, we demonstrate that the interaction between laforin and malin is a regulated process that is modulated by the AMP-activated protein kinase (AMPK). These findings provide further insights into the critical role of the laforin-malin complex in the control of glycogen metabolism and unravel a novel link between the energy sensor AMPK and glycogen metabolism. These data advance our understanding of the functional role of laforin and malin, which hopefully will facilitate the development of appropriate LD therapies.
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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/AMP-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/EPM2A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen,
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/NHLRC1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1460-2083
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pubmed:author |
pubmed-author:AguadoCarmenC,
pubmed-author:Criado GarciaOlgaO,
pubmed-author:DominguezJorgeJ,
pubmed-author:Fernandez-SanchezMaria ElenaME,
pubmed-author:Garcia-FojedaBelenB,
pubmed-author:Garcia-RochaMarM,
pubmed-author:Gimeno-AlcañizJosé VicenteJV,
pubmed-author:GuinovartJoan JosepJJ,
pubmed-author:KnechtErwinE,
pubmed-author:Rodriguez de CórdobaSantiagoS,
pubmed-author:RosSusanaS,
pubmed-author:Sanchez-PirisMaribelM,
pubmed-author:SanzPascualP,
pubmed-author:SerratosaJoseJ,
pubmed-author:Solaz-FusterMaria CarmenMC,
pubmed-author:VilchezDavidD
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
17
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
667-78
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:18029386-AMP-Activated Protein Kinases,
pubmed-meshheading:18029386-Adenoviridae,
pubmed-meshheading:18029386-Amino Acid Sequence,
pubmed-meshheading:18029386-Animals,
pubmed-meshheading:18029386-Binding Sites,
pubmed-meshheading:18029386-Carrier Proteins,
pubmed-meshheading:18029386-Cell Line,
pubmed-meshheading:18029386-Cell Line, Tumor,
pubmed-meshheading:18029386-Cell Physiological Phenomena,
pubmed-meshheading:18029386-Escherichia coli,
pubmed-meshheading:18029386-Glycogen,
pubmed-meshheading:18029386-Green Fluorescent Proteins,
pubmed-meshheading:18029386-Humans,
pubmed-meshheading:18029386-Kidney,
pubmed-meshheading:18029386-Models, Biological,
pubmed-meshheading:18029386-Molecular Sequence Data,
pubmed-meshheading:18029386-Multienzyme Complexes,
pubmed-meshheading:18029386-Mutation,
pubmed-meshheading:18029386-Phosphorylation,
pubmed-meshheading:18029386-Protein Binding,
pubmed-meshheading:18029386-Protein Structure, Tertiary,
pubmed-meshheading:18029386-Protein Tyrosine Phosphatases, Non-Receptor,
pubmed-meshheading:18029386-Protein-Serine-Threonine Kinases,
pubmed-meshheading:18029386-Rats,
pubmed-meshheading:18029386-Recombinant Fusion Proteins,
pubmed-meshheading:18029386-Statistics as Topic,
pubmed-meshheading:18029386-Transfection,
pubmed-meshheading:18029386-Two-Hybrid System Techniques,
pubmed-meshheading:18029386-Ubiquitination
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pubmed:year |
2008
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pubmed:articleTitle |
Regulation of glycogen synthesis by the laforin-malin complex is modulated by the AMP-activated protein kinase pathway.
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pubmed:affiliation |
Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas, and CIBERER-ISCIII, Jaime Roig 11, Valencia 46010, Spain.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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