The conserved Myc box 2 and Myc box 3 regions are important, but not essential, for Myc function in vivo.
Myc proto-oncoproteins are important regulators of growth and proliferation in development. Their functions have been evolutionarily conserved from insects to vertebrates, although the sequence conservation is limited to a few short domains. Here, we analyze the requirement for the most highly conserved domains, called Myc boxes 2 and 3 (MB2 and MB3), and for the weakly conserved N-terminus for the biological activity of the single Drosophila Myc protein in the animal in vivo. We find that a Myc mutant lacking the N-terminus retains very little activity, whereas Myc transgenes carrying a deletion of MB3 have a moderately increased ability to promote growth and apoptosis; mutation of MB2 reduces transcriptional output and the biological activities of Myc. Surprisingly though, Myc without MB2 retains enough activity to partially rescue the lethality of a Myc null mutation. Thus, although MB2 and MB3 are highly conserved in evolution, loss of either domain has comparatively mild consequences on Myc activity in vivo.
Schwinkendorf
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Zoologisches Institut, Universität Zürich, Zürich, Switzerland.
Gallant
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D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D017124:Conserved Sequence; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development* / Q000648:ultrastructure; D005123:Eye / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D018507:Gene Expression Regulation, Developmental; D020043:Genes, Essential; D005816:Genetic Complementation Test; D005838:Genotype; D020287:In Situ Nick-End Labeling; D008855:Microscopy, Electron, Scanning; D008969:Molecular Sequence Data; D009154:Mutation; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014921:Wings, Animal / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure
D029721:Drosophila Proteins; D016271:Proto-Oncogene Proteins c-myc