DCAF8, a novel MuRF1 interaction partner, promotes muscle atrophy

Marcel Nowak, Benjamin Suenkel, Pablo Porras, Rebekka Migotti, Franziska Schmidt, Melanie Kny, Xiaoxi Zhu, Erich E. Wanker, Gunnar Dittmar, Jens Fielitz*, Thomas Sommer*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

18 Citations (Scopus)


The muscle-specific RING-finger protein MuRF1 (also known as TRIM63) constitutes a bona fide ubiquitin ligase that routes proteins like several different myosin heavy chain proteins (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. Importantly, similar to what is seen for MuRF1, DCAF8 levels increase during atrophy, and the downregulation 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 for 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 Cul4A-containing ring ubiquitin ligase complex (CRL4A).

Original languageEnglish
Article numberjcs233395
JournalJournal of Cell Science
Issue number17
Publication statusPublished - Sept 2019
Externally publishedYes


  • Atrophy
  • Cullin
  • MuRF1


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