| First Author | Enwere EK | Year | 2012 |
| Journal | Sci Signal | Volume | 5 |
| Issue | 246 | Pages | ra75 |
| PubMed ID | 23074266 | Mgi Jnum | J:258575 |
| Mgi Id | MGI:6142124 | Doi | 10.1126/scisignal.2003086 |
| Citation | Enwere EK, et al. (2012) TWEAK and cIAP1 regulate myoblast fusion through the noncanonical NF-kappaB signaling pathway. Sci Signal 5(246):ra75 |
| abstractText | The fusion of mononucleated muscle progenitor cells (myoblasts) into multinucleated muscle fibers is a critical aspect of muscle development and regeneration. We identified the noncanonical nuclear factor kappaB (NF-kappaB) pathway as a signaling axis that drives the recruitment of myoblasts into new muscle fibers. Loss of cellular inhibitor of apoptosis 1 (cIAP1) protein led to constitutive activation of the noncanonical NF-kappaB pathway and an increase in the number of nuclei per myotube. Knockdown of essential mediators of NF-kappaB signaling, such as p100, RelB, inhibitor of kappaB kinase alpha, and NF-kappaB-inducing kinase, attenuated myoblast fusion in wild-type myoblasts. In contrast, the extent of myoblast fusion was increased when the activity of the noncanonical NF-kappaB pathway was enhanced by increasing the abundance of p52 and RelB or decreasing the abundance of tumor necrosis factor (TNF) receptor-associated factor 3, an inhibitor of this pathway. Low concentrations of the cytokine TNF-like weak inducer of apoptosis (TWEAK), which preferentially activates the noncanonical NF-kappaB pathway, also increased myoblast fusion, without causing atrophy or impairing myogenesis. These results identify roles for TWEAK, cIAP1, and noncanonical NF-kappaB signaling in the regulation of myoblast fusion and highlight a role for cytokine signaling during adult skeletal myogenesis. |
