E. Chalaux et al., JUNB IS INVOLVED IN THE INHIBITION OF MYOGENIC DIFFERENTIATION BY BONE MORPHOGENETIC PROTEIN-2, The Journal of biological chemistry, 273(1), 1998, pp. 537-543
Bone morphogenetic proteins (BMPs) constitute a family of multifunctio
nal growth and differentiation factors structurally related to transfo
rming growth factor-beta. BMPs were first identified by their osteoind
uctive effects, inducing ectopic bone formation when implanted in skel
etal muscle, and have an important role as regulators of skeletal deve
lopment in vivo, In vitro, BMP-S is able to transdifferentiate myogeni
c C2C12 cells into the osteoblastic phenotype, In this report, we show
that the osteoinductive effects of BMP-S in C2C12 cells are mediated
by bone morphogenetic protein receptor type-LA in combination with bot
h activin receptor type II and bone morphogenetic protein receptor typ
e II, We also analyzed the expression levels of nuclear protooncogenes
to understand early transcriptional events induced by BMP-2. We show
that junB is an immediate early gene induced by BMP-2 and transforming
growth factor-beta. BMP-2 induces transcriptional activation of JunB
expression as early as 30 min after Ligand addition, reaching maximal
levels after 90 min, Increase of JunB mRNA correlates with a higher AP
-1 binding activity. Furthermore, ectopic overexpression of JunB is su
fficient to inhibit expression of myoblast differentiation markers in
C2C12 cells, These data, taken together, show the involvement of JunB
in the early steps of inhibition of myogenic differentiation induced b
y transforming growth factor-beta family members.