Max-independent functions of Myc in Drosophila melanogaster.
Myc proteins are powerful proto-oncoproteins and important promoters of growth and proliferation during normal development. They are thought to exercise their effects upon binding to their partner protein Max, and their activities are largely antagonized by complexes of Max with Mnt or an Mxd family protein. Although the biological functions of Myc, Mxd and Mnt have been intensively studied, comparatively little is known about the in vivo role of Max. Here we generate Max loss-of-function and reduction-of-function mutations in Drosophila melanogaster to address the contribution of Max to Myc-dependent growth control. We find that many biological activities of Myc do not, or only partly, require the association with Max--for example, the control of endoreplication and cell competition-and that a Myc mutant that does not interact with Max retains substantial biological activity. We further show that Myc can control RNA polymerase III independently of Max, which explains some of Myc's observed biological activities. These studies show the ability of Myc to function independently of Max in vivo and thus change the current model of Max network function.
Steiger
Dominik
D
Zoologisches Institut, Universitat Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
Furrer
Michael
M
Schwinkendorf
Daniela
D
Gallant
Peter
P
D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D008675:Metamorphosis, Biological; D010641:Phenotype; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D012320:RNA Polymerase III / Q000378:metabolism; D012097:Repressor Proteins / Q000502:physiology; D019076:Transgenes; D014921:Wings, Animal
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D029721:Drosophila Proteins; C106465:MNT protein, human; C102283:Max protein, Drosophila; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; D012320:RNA Polymerase III