Cargando…
The Laforin–Malin Complex, Involved in Lafora Disease, Promotes the Incorporation of K63-linked Ubiquitin Chains into AMP-activated Protein Kinase β Subunits
Lafora progressive myoclonus epilepsy is a fatal neurodegenerative disorder caused by defects in the function of at least two proteins: laforin, a dual-specificity protein phosphatase, and malin, an E3-ubiquitin ligase. In this study, we report that a functional laforin–malin complex promotes the ub...
Autores principales: | , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2010
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2912345/ https://www.ncbi.nlm.nih.gov/pubmed/20534808 http://dx.doi.org/10.1091/mbc.E10-03-0227 |
_version_ | 1782184586403381248 |
---|---|
author | Moreno, Daniel Towler, Mhairi C. Hardie, D. Grahame Knecht, Erwin Sanz, Pascual |
author_facet | Moreno, Daniel Towler, Mhairi C. Hardie, D. Grahame Knecht, Erwin Sanz, Pascual |
author_sort | Moreno, Daniel |
collection | PubMed |
description | Lafora progressive myoclonus epilepsy is a fatal neurodegenerative disorder caused by defects in the function of at least two proteins: laforin, a dual-specificity protein phosphatase, and malin, an E3-ubiquitin ligase. In this study, we report that a functional laforin–malin complex promotes the ubiquitination of AMP-activated protein kinase (AMPK), a serine/threonine protein kinase that acts as a sensor of cellular energy status. This reaction occurs when any of the three AMPK subunits (α, β, and γ) are expressed individually in the cell, and it also occurs on AMPKβ when it is part of a heterotrimeric complex. We also report that the laforin–malin complex promotes the formation of K63-linked ubiquitin chains, which are not involved in proteasome degradation. On the contrary, this modification increases the steady-state levels of at least AMPKβ subunit, possibly because it leads to the accumulation of this protein into inclusion bodies. These results suggest that the modification introduced by the laforin–malin complex could affect the subcellular distribution of AMPKβ subunits. |
format | Text |
id | pubmed-2912345 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-29123452010-10-16 The Laforin–Malin Complex, Involved in Lafora Disease, Promotes the Incorporation of K63-linked Ubiquitin Chains into AMP-activated Protein Kinase β Subunits Moreno, Daniel Towler, Mhairi C. Hardie, D. Grahame Knecht, Erwin Sanz, Pascual Mol Biol Cell Articles Lafora progressive myoclonus epilepsy is a fatal neurodegenerative disorder caused by defects in the function of at least two proteins: laforin, a dual-specificity protein phosphatase, and malin, an E3-ubiquitin ligase. In this study, we report that a functional laforin–malin complex promotes the ubiquitination of AMP-activated protein kinase (AMPK), a serine/threonine protein kinase that acts as a sensor of cellular energy status. This reaction occurs when any of the three AMPK subunits (α, β, and γ) are expressed individually in the cell, and it also occurs on AMPKβ when it is part of a heterotrimeric complex. We also report that the laforin–malin complex promotes the formation of K63-linked ubiquitin chains, which are not involved in proteasome degradation. On the contrary, this modification increases the steady-state levels of at least AMPKβ subunit, possibly because it leads to the accumulation of this protein into inclusion bodies. These results suggest that the modification introduced by the laforin–malin complex could affect the subcellular distribution of AMPKβ subunits. The American Society for Cell Biology 2010-08-01 /pmc/articles/PMC2912345/ /pubmed/20534808 http://dx.doi.org/10.1091/mbc.E10-03-0227 Text en © 2010 by The American Society for Cell Biology |
spellingShingle | Articles Moreno, Daniel Towler, Mhairi C. Hardie, D. Grahame Knecht, Erwin Sanz, Pascual The Laforin–Malin Complex, Involved in Lafora Disease, Promotes the Incorporation of K63-linked Ubiquitin Chains into AMP-activated Protein Kinase β Subunits |
title | The Laforin–Malin Complex, Involved in Lafora Disease, Promotes the Incorporation of K63-linked Ubiquitin Chains into AMP-activated Protein Kinase β Subunits |
title_full | The Laforin–Malin Complex, Involved in Lafora Disease, Promotes the Incorporation of K63-linked Ubiquitin Chains into AMP-activated Protein Kinase β Subunits |
title_fullStr | The Laforin–Malin Complex, Involved in Lafora Disease, Promotes the Incorporation of K63-linked Ubiquitin Chains into AMP-activated Protein Kinase β Subunits |
title_full_unstemmed | The Laforin–Malin Complex, Involved in Lafora Disease, Promotes the Incorporation of K63-linked Ubiquitin Chains into AMP-activated Protein Kinase β Subunits |
title_short | The Laforin–Malin Complex, Involved in Lafora Disease, Promotes the Incorporation of K63-linked Ubiquitin Chains into AMP-activated Protein Kinase β Subunits |
title_sort | laforin–malin complex, involved in lafora disease, promotes the incorporation of k63-linked ubiquitin chains into amp-activated protein kinase β subunits |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2912345/ https://www.ncbi.nlm.nih.gov/pubmed/20534808 http://dx.doi.org/10.1091/mbc.E10-03-0227 |
work_keys_str_mv | AT morenodaniel thelaforinmalincomplexinvolvedinlaforadiseasepromotestheincorporationofk63linkedubiquitinchainsintoampactivatedproteinkinasebsubunits AT towlermhairic thelaforinmalincomplexinvolvedinlaforadiseasepromotestheincorporationofk63linkedubiquitinchainsintoampactivatedproteinkinasebsubunits AT hardiedgrahame thelaforinmalincomplexinvolvedinlaforadiseasepromotestheincorporationofk63linkedubiquitinchainsintoampactivatedproteinkinasebsubunits AT knechterwin thelaforinmalincomplexinvolvedinlaforadiseasepromotestheincorporationofk63linkedubiquitinchainsintoampactivatedproteinkinasebsubunits AT sanzpascual thelaforinmalincomplexinvolvedinlaforadiseasepromotestheincorporationofk63linkedubiquitinchainsintoampactivatedproteinkinasebsubunits AT morenodaniel laforinmalincomplexinvolvedinlaforadiseasepromotestheincorporationofk63linkedubiquitinchainsintoampactivatedproteinkinasebsubunits AT towlermhairic laforinmalincomplexinvolvedinlaforadiseasepromotestheincorporationofk63linkedubiquitinchainsintoampactivatedproteinkinasebsubunits AT hardiedgrahame laforinmalincomplexinvolvedinlaforadiseasepromotestheincorporationofk63linkedubiquitinchainsintoampactivatedproteinkinasebsubunits AT knechterwin laforinmalincomplexinvolvedinlaforadiseasepromotestheincorporationofk63linkedubiquitinchainsintoampactivatedproteinkinasebsubunits AT sanzpascual laforinmalincomplexinvolvedinlaforadiseasepromotestheincorporationofk63linkedubiquitinchainsintoampactivatedproteinkinasebsubunits |