Transactivation-defective c-MycS retains the ability to regulate proliferation and apoptosis.
Transcriptional activation by c-Myc through specific E box elements is thought to be essential for its biological role. However, c-MycS is unable to activate transcription through these elements and yet retains the ability to stimulate proliferation, induce anchorage-independent growth, and induce apoptosis. In addition, c-MycS retains the ability to repress transcription of several specific promoters. Furthermore, c-MycS can rescue the c-myc null phenotype in fibroblasts with homozygous deletion of c-myc. Taken together, our data argue against the paradigm that all of the biological functions of c-Myc are mediated by transcriptional activation of specific target genes through E box elements.
Xiao
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Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2175 USA.
Claassen
G
G
Shi
J
J
Adachi
S
S
Sedivy
J
J
Hann
S R
SR
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005786:Gene Expression Regulation; D016259:Genes, myc; D016158:Genes, p53; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D009955:Ornithine Decarboxylase / Q000235:genetics; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology*; D011498:Protein Precursors / Q000235:genetics; D011506:Proteins / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology; D020218:Response Elements / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D017384:Sequence Deletion; D013947:Thymosin / Q000031:analogs & derivatives / Q000235:genetics; D015533:Transcriptional Activation; D014162:Transfection; D000097642:GADD45 Proteins
D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D009955:Ornithine Decarboxylase; D020033:Protein Isoforms; D011498:Protein Precursors; D011506:Proteins; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D013947:Thymosin; D000097642:GADD45 Proteins; C066709:GAS1 protein, S cerevisiae; C040782:prothymosin alpha