Research ArticlePhysiology

TWEAK and cIAP1 Regulate Myoblast Fusion Through the Noncanonical NF-κB Signaling Pathway

Sci. Signal.  16 Oct 2012:
Vol. 5, Issue 246, pp. ra75
DOI: 10.1126/scisignal.2003086

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Noncanonical NF-κB Signaling Gets Muscular

Skeletal muscle development (myogenesis) occurs through the fusion of single myoblasts to produce a multinucleated muscle fiber. Previous studies suggested that the canonical NF-κB pathway inhibits myogenesis. Enwere et al. showed that loss or inhibition of cIAP1, an inhibitor of the noncanonical NF-κB pathway, increased the recruitment of myoblasts into myotubes. Overexpression of components of noncanonical signaling increased myoblast fusion. Furthermore, at low concentrations, the cytokine TWEAK preferentially activated the noncanonical pathway and also increased myoblast fusion. In addition to highlighting antagonism between canonical and noncanonical NF-κB signaling in regulating myogenesis, this study suggests that small-molecule IAP antagonists or administration of TWEAK could provide potential therapies for muscle injury and degenerative diseases.