Abstract
Bone morphogenetic protein-2 (BMP-2) induces a switch in differentiation of mesenchymal cells from the myogenic to the osteogenic lineage. Here we describe that in C2C12 cells, BMP-2 decreases myogenin expression induced by des-(1,3) insulin-like growth factor-1 (des-(1,3)IGF-1) or ectopically expressed from a constitutive promoter, even in conditions where myogenin mRNA levels were unaffected. Addition of BMP-2 decreases myogenin protein half-life to 50%, whereas proteasome inhibitors abolish these effects. Forced expression of Id1, either by transient transfection or under the control of an inducible system, causes degradation of myogenin in the absence of BMP-2. In contrast, E47 overexpression blocks the inhibitory effect of BMP-2 on myogenin levels. Finally, expression of E47 in 293 cells stabilizes myogenin, an effect that is dependent on the heterodimerization mediated by their helix-loop-helix. Our findings indicate that induction of Id1 not only blocks transcriptional activity but also induces myogenin degradation by blocking formation of myogenin-E47 protein complexes.
Highlights
Mesenchymal cells differentiate into distinct cell types, such as adipocytes, osteoblasts, or myoblasts
Bone morphogenetic protein-2 (BMP-2) Induces the Degradation of Myogenin in C2C12 Cells—C2C12 cells incubated for 3 days with a limited supply of growth factors (2% horse serum) or in the presence of 2 nM des-(1,3)IGF-1 [15, 34] differentiated to multinucleated myotubes
BMP-2 induces the osteoblastic phenotype of mesenchymal cells and causes a concomitant blockade of the myogenic program both in vivo and in vitro [1, 16, 36]
Summary
Mesenchymal cells differentiate into distinct cell types, such as adipocytes, osteoblasts, or myoblasts. Forced expression of Id1, either by transient transfection or under the control of an inducible system, causes degradation of myogenin in the absence of BMP-2. BMP-2 Induces the Degradation of Myogenin in C2C12 Cells—C2C12 cells incubated for 3 days with a limited supply of growth factors (2% horse serum) or in the presence of 2 nM des-(1,3)IGF-1 (a potent myogenic inducer) [15, 34] differentiated to multinucleated myotubes.
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