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DCAF8, a novel MuRF1 interaction partner, promotes muscle atrophy

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Item Type:Article
Title:DCAF8, a novel MuRF1 interaction partner, promotes muscle atrophy
Creators Name:Nowak, M. and Suenkel, B. and Porras, P. and Migotti, R. and Schmidt, F. and Kny, M. and Zhu, X. and Wanker, E.E. and Dittmar, G. and Fielitz, J. and Sommer, T.
Abstract:The muscle-specific RING-finger protein MuRF1 constitutes a bona fide ubiquitin ligase that routes proteins like Myosin heavy chain (MyHC) to proteasomal degradation during muscle atrophy. In two unbiased screens we identified DCAF8 as a new MuRF1 binding partner. MuRF1 physically interacts with DCAF8 and both proteins localize to overlapping structures in muscle cells. Noteworthy, similar to MuRF1, DCAF8 levels increase during atrophy and the down-regulation of either protein substantially impedes muscle wasting and MyHC degradation in C2C12 myotubes, a model system for muscle differentiation and atrophy. DCAF proteins typically serve as substrate receptors in Cullin 4-type (Cul4) ubiquitin ligases (CRL) and we demonstrate that DCAF8 and MuRF1 associate with the subunits of such a protein complex. Because genetic downregulation of DCAF8 and inhibition of Cullin activity also impair myotube atrophy in C2C12 cells, our data imply that the DCAF8 promotes muscle wasting by targeting proteins like MyHC as an integral substrate receptor of a CRL4A ubiquitin ligase.
Keywords:Atrophy, Cullin, MuRF1, Animals, Mice, Rats
Source:Journal of Cell Science
ISSN:0021-9533
Publisher:Company of Biologists
Volume:132
Number:17
Page Range:jcs233395
Date:6 September 2019
Additional Information:Copyright © 2019 The Authors. Published by The Company of Biologists Ltd.
Official Publication:https://doi.org/10.1242/jcs.233395
PubMed:View item in PubMed

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