Identification of PDLIM7 as a Nedd4-1 Substrate in the Regulation of Skeletal Muscle Mass

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2016-11

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Skeletal muscle atrophy occurs both as a natural consequence of muscle disuse and aging, and as a pathophysiological response to acute and chronic disease. The ubiquitin proteasome system is the predominant proteolytic machinery responsible for atrophy of skeletal muscle and Nedd4-1 is one of a series of E3 ubiquitin ligases known to mediate inactivity-induced muscle wasting. Muscle substrates of Nedd4-1, and mechanisms by which Nedd4-1 regulates muscle mass, are poorly understood. In the present study, I identified PDLIM7 as a novel target of Nedd4- 1 in skeletal muscle. Nedd4-1 expression in muscle atrophied by denervation is coincident with a decrease in PDLIM7, and PDLIM7 protein levels are stabilized in denervated muscle of Nedd4-1 knockout mice. These results identify PDLIM7 as a bona fide skeletal muscle substrate of Nedd4-1 and suggest that this interaction may underlie the progression of skeletal muscle atrophy, offering a potential therapeutic target to attenuate its onset.

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