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.
La Rocca
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SA
Cancer Research Campaign Beatson Laboratories, Beatson Institute for Cancer Research, Wolfson Laboratory for Molecular Pathology, Bearsden, Glasgow, UK.
Crouch
D H
DH
Gillespie
D A
DA
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