MassIVE MSV000079730

Partial Public PXD004169

Gadd45a Promotes Skeletal Muscle Atrophy by Forming a Complex with the Protein Kinase MEKK4

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Description

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 fiber proteins that associate with Gadd45a as it induces skeletal muscle atrophy in living mice. We found that Gadd45a interacts with multiple proteins in skeletal muscle fibers, including, most prominently, the MAP kinase kinase kinase MEKK4. Furthermore, by forming a complex with MEKK4 in skeletal muscle fibers, Gadd45a increases MEKK4 protein kinase activity, which is 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 way that skeletal muscle atrophy occurs at the molecular level. [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Gadd45a ; Muscle Atrophy ; Protein Kinase MEKK4

Contact

Principal Investigators:
(in alphabetical order) 		Christopher M. Adams
Submitting User: bschilling

Publications

Bullard SA, Seo S, Schilling B, Dyle MC, Dierdorff JM, Ebert SM, DeLau AD, Gibson BW, Adams CM.
Gadd45a Promotes Skeletal Muscle Atrophy by Forming a Complex with the Protein Kinase MEKK4.
J. Biol. Chem. Epub 2016 Jun 29.

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