c-Myc inhibits myogenic differentiation and myoD expression by a mechanism which can be dissociated from cell transformation.

Abstract:

: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.

journal_name

Oncogene

journal_title

Oncogene

authors

La Rocca SA,Crouch DH,Gillespie DA

subject

Has Abstract

pub_date

1994-12-01 00:00:00

pages

3499-508

issue

12

eissn

0950-9232

issn

1476-5594

journal_volume

9

pub_type

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