Gadd45a Protein Promotes Skeletal Muscle Atrophy by Forming a Complex with the Protein Kinase MEKK4
| Autor: | Steven A. Bullard, Michael C. Dyle, Scott M. Ebert, Christopher M. Adams, Bradford W. Gibson, Austin D. DeLau, Jason M. Dierdorff, Seongjin Seo, Birgit Schilling |
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| Rok vydání: | 2016 |
| Předmět: |
muscle atrophy
0301 basic medicine skeletal muscle metabolism muscle Muscle Fibers Skeletal Cell Cycle Proteins Papers of the Week MAP Kinase Kinase Kinase 4 Biochemistry Mice 03 medical and health sciences 0302 clinical medicine Atrophy medicine Animals MEKK4 Myocyte mass spectrometry (MS) skeletal muscle Nuclear protein Protein kinase A Molecular Biology Chemistry Kinase aging Nuclear Proteins Skeletal muscle Cell Biology medicine.disease Muscle atrophy Cell biology Muscular Atrophy 030104 developmental biology medicine.anatomical_structure Multiprotein Complexes medicine.symptom ITGA7 030217 neurology & neurosurgery Gadd45a |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m116.740308 |
| Popis: | Skeletal muscle atrophy is a serious and highly prevalent condition that remains poorly understood at the molecular level. Previous work found that skeletal muscle atrophy involves an increase in skeletal muscle Gadd45a expression, which is necessary and sufficient for skeletal muscle fiber atrophy. However, the direct mechanism by which Gadd45a promotes skeletal muscle atrophy was unknown. To address this question, we biochemically isolated skeletal muscle proteins that associate with Gadd45a as it induces atrophy in mouse skeletal muscle fibers in vivo. We found that Gadd45a interacts with multiple proteins in skeletal muscle fibers, including, most prominently, MEKK4, a mitogen-activated protein kinase kinase kinase that was not previously known to play a role in skeletal muscle atrophy. Furthermore, we found that, by forming a complex with MEKK4 in skeletal muscle fibers, Gadd45a increases MEKK4 protein kinase activity, which is both sufficient to induce skeletal muscle fiber atrophy and required for Gadd45a-mediated skeletal muscle fiber atrophy. Together, these results identify a direct biochemical mechanism by which Gadd45a induces skeletal muscle atrophy and provide new insight into the way that skeletal muscle atrophy occurs at the molecular level. |
| Databáze: | OpenAIRE |
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