TRAF6 regulates proliferation and differentiation of skeletal myoblasts.
We could recently demonstrate an important role of receptor interacting protein-2 (RIP2), an activator of nuclear factor kappa B (NF-κB) and a target of activated receptors of the tumor necrosis factor receptor (TNFR) type, in myogenic differentiation and regeneration. Here, we analyze a potential role of TNFR associated factor 6 (TRAF6), which also associates with the cytoplasmic domain of TNFR type, but also IL-1-R and TLR type receptors, and activates NF-κB, in these processes. Specifically, we show that during myogenic differentiation in vitro, traf6 gene expression is downregulated in normal myoblasts, but not in rhabdomyosarcoma cells, suggesting a role of the TRAF6 protein in this process. Inhibition of traf6 expression using specific siRNAs led to an inhibition of both myoblast proliferation and differentiation, whereas inhibition of the TRAF6 effector NF-κB alone in our system only blocked proliferation. Finally, we demonstrate that the traf6 gene is downregulated in skeletal muscle tissue of the dystrophic mdx mouse. Taken together, these data argue for a role of TRAF6 in the regulation of skeletal muscle differentiation and regeneration.
Charité-University Medicine Berlin, Institute of Physiology, Thielallee 71, D-14195 Berlin, Germany.
Tobias
T
Mueck
Felicitas
F
Berger
Ingrid
I
Buechsler
Ralitsa S
RS
Valchanova
Lorena
L
Landuzzi
Pier-Luigi
PL
Lollini
Karin
K
Klingel
Barbara
B
Munz
D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D006801:Humans; D051379:Mice; D024510:Muscle Development / Q000235:genetics*; D019042:Muscle Neoplasms / Q000235:genetics; D032448:Myoblasts, Skeletal / Q000166:cytology* / Q000502:physiology; D016328:NF-kappa B / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D012038:Regeneration / Q000235:genetics; D012208:Rhabdomyosarcoma / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics / Q000378:metabolism*
D016328:NF-kappa B; D034741:RNA, Small Interfering; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D048029:TNF Receptor-Associated Factor 6; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C506255:Ripk2 protein, mouse