Human c-Myc isoforms differentially regulate cell growth and apoptosis in Drosophila melanogaster.
The human c-myc proto-oncogene, implicated in the control of many cellular processes including cell growth and apoptosis, encodes three isoforms which differ in their N-terminal region. The functions of these isoforms have never been addressed in vivo. Here, we used Drosophila melanogaster to examine their functions in a fully integrated system. First, we established that the human c-Myc protein can rescue lethal mutations of the Drosophila myc ortholog, dmyc, demonstrating the biological relevance of this model. Then, we characterized a new lethal dmyc insertion allele, which permits expression of human c-Myc in place of dMyc and used it to compare physiological activities of these isoforms in whole-organism rescue, transcription, cell growth, and apoptosis. These isoforms differ both quantitatively and qualitatively. Most remarkably, while the small c-MycS form truncated for much of its N-terminal trans-activation domain efficiently rescued viability and cell growth, it did not induce detectable programmed cell death. Our data indicate that the main functional difference between c-Myc isoforms resides in their apoptotic properties and that the N-terminal region, containing the conserved MbI motif, is decisive in governing the choice between growth and death.
Benassayag
C
C
Centre de Biologie du Développement, CNRS UMR 5547, Université Paul Sabatier, 118 Rte. de Narbonne, 31062 Toulouse Cedex, France.
Montero
L
L
Colombié
N
N
Gallant
P
P
Cribbs
D
D
Morello
D
D
D000483:Alleles; D020816:Amino Acid Motifs; D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D049109:Cell Proliferation; D003001:Cloning, Molecular; D004331:Drosophila melanogaster; D005091:Exons; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008938:Mitosis; D008957:Models, Genetic; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry*; D012313:RNA / Q000737:chemistry; D011995:Recombination, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013696:Temperature; D014158:Transcription, Genetic; D019076:Transgenes
C000715470:MAS1 protein, human; D020033:Protein Isoforms; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D049452:Green Fluorescent Proteins; D012313:RNA