c-Myc inhibits myogenic differentiation and myoD expression by a mechanism which can be dissociated from cell transformation.
The c-Myc oncoprotein is a basic-helix-loop-helix-leucine zipper (b-HLH-LZ) transcription factor involved in regulating cell proliferation and differentiation. We have used retrovirus-mediated gene transfer to investigate the effect of ectopic c-Myc expression on the spontaneous differentiation of primary quail myoblasts in vitro. Unlike normal myoblasts, c-Myc-expressing myoblasts are unable to form myotubes or express muscle-specific genes, such as myosin, and show severely reduced expression of the myogenic regulatory factors myoD, myogenin, and myf5. The c-Myc leucine zipper (LZ) motif is essential for the differentiation block since myoblasts expressing a mutant with a partial deletion of this region, c-Myc delta 7, differentiate and express myoD family regulators and muscle-specific genes normally. Remarkably, c-Myc delta 7, like wild-type c-Myc, retains the capacity to transform the growth phenotype of myoblasts, and associates with the b-HLH-LZ Myc partner protein Max in transformed cells. We conclude that the block to myogenic differentiation induced by c-Myc can be dissociated from cell transformation per se, and that this attribute correlates more closely with down-regulation of myoD family gene expression. These findings are discussed in the light of current models of Myc function.
Cancer Research Campaign Beatson Laboratories, Beatson Institute for Cancer Research, Wolfson Laboratory for Molecular Pathology, Bearsden, Glasgow, UK.
S A
SA
La Rocca
D H
DH
Crouch
D A
DA
Gillespie
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002461:Cell Line, Transformed; D003370:Coturnix; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D009132:Muscles / Q000166:cytology*; D017570:MyoD Protein / Q000096:biosynthesis / Q000235:genetics*; D009838:Oligodeoxyribonucleotides; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*
D017570:MyoD Protein; D009838:Oligodeoxyribonucleotides; D016271:Proto-Oncogene Proteins c-myc