TY - JOUR
T1 - TRAF6 regulates proliferation and differentiation of skeletal myoblasts
AU - Mueck, Tobias
AU - Berger, Felicitas
AU - Buechsler, Ingrid
AU - Valchanova, Ralitsa S.
AU - Landuzzi, Lorena
AU - Lollini, Pier Luigi
AU - Klingel, Karin
AU - Munz, Barbara
PY - 2011/2
Y1 - 2011/2
N2 - 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.
AB - 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.
KW - Myogenic differentiation
KW - Rhabdomyosarcoma
KW - TRAF6
UR - http://www.scopus.com/inward/record.url?scp=79551687102&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79551687102&partnerID=8YFLogxK
U2 - 10.1016/j.diff.2010.11.002
DO - 10.1016/j.diff.2010.11.002
M3 - Article
C2 - 21131124
AN - SCOPUS:79551687102
VL - 81
SP - 99
EP - 106
JO - Differentiation
JF - Differentiation
SN - 0301-4681
IS - 2
ER -