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Science 21 October 1988: Vol. 242. no. 4877, pp. 405 - 411 DOI: 10.1126/science.3175662
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Articles
Science, Vol 242, Issue 4877, 405-411
Copyright © 1988 by American Association for the Advancement of Science
MyoD1: a nuclear phosphoprotein requiring a Myc homology region to convert fibroblasts to myoblasts
SJ Tapscott,
RL Davis,
MJ Thayer,
PF Cheng,
H Weintraub,
and
AB Lassar
Department of Genetics, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Expression of a complementary DNA (cDNA) encoding the mouse MyoD1 protein in a variety of fibroblast and adipoblast cell lines converts them to myogenic cells. Polyclonal antisera to fusion proteins containing the MyoD1 sequence show that MyoD1 is a phosphoprotein present in the nuclei of proliferating myoblasts and differentiated myotubes but not expressed in 10T1/2 fibroblasts or other nonmuscle cell types. Functional domains of the MyoD1 protein were analyzed by site-directed deletional mutagenesis of the MyoD1 cDNA. Deletion of a highly basic region (residues 102 to 135) interferes with both nuclear localization and induction of myogenesis. Deletion of a short region (residues 143 to 162) that is similar to a conserved region in the c-Myc family of proteins eliminates the ability of the MyoD1 protein to initiate myogenesis but does not alter nuclear localization. Deletions of regions spanning the remainder of MyoD1 did not affect nuclear localization and did not inhibit myogenesis. Furthermore, expression of only 68 amino acids of MyoD1, containing the basic and the Myc similarity domains, is sufficient to activate myogenesis in stably transfected 10T1/2 cells. Genetic analysis maps the MyoD1 gene to mouse chromosome 7 and human chromosome 11.
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- Stabilization of MyoD by Direct Binding to p57Kip2.
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