Myogenin protein stability is decreased by BMP-2 through a mechanism implicating Id1.
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.
Viñals
Francesc
F
Unitat de Bioquímica, Departament de Ciències Fisiològiques II, Campus de Bellvitge, Universitat de Barcelona, E-08907 L'Hospitalet de Llobregat, Spain.
Ventura
Francesc
F
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1; D051379:Mice; D018008:Myogenin / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D012097:Repressor Proteins / Q000502:physiology*; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; C497453:ID1 protein, human; C497455:Idb1 protein, mouse; D051798:Inhibitor of Differentiation Protein 1; C503799:MYOG protein, human; C503801:Myog protein, mouse; D018008:Myogenin; D011994:Recombinant Proteins; D012097:Repressor Proteins; D051820:TCF Transcription Factors; C544912:TCF7L1 protein, human; C544913:Tcf7l1 protein, mouse; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D046988:Proteasome Endopeptidase Complex