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Max-independent functions of Myc in Drosophila melanogaster

Abstract

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.

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Figure 1: Max null mutants are delayed in development and die before eclosion.
Figure 2: Loss of Max leads to milder defects than simultaneous loss of Myc and Mnt.
Figure 3: C-terminally truncated Myc does not interact with Max but retains partial function.
Figure 4: Max mutant mitotic clones grow better than dm Mnt double-mutant clones.
Figure 5: Myc overexpression in the eye induces growth and apoptosis in a largely Max-dependent and Max-independent manner, respectively.
Figure 6: Myc interacts with Brf and can induce RNA Pol III targets independently of Max.

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Acknowledgements

We thank S. Pierce and R. Eisenman (Fred Hutchinson Cancer Research Center) for providing us with a dm Mnt recombinant chromosome before publication; K. Basler, J. Bischof (University of Zürich), E. Hafen, H. Stocker (ETH Zürich), S. Takada (MD Anderson) and D. Stein (University of Texas, Austin) for flies and antibodies; H. Stocker and C. Hugentobler for advice; N. Müller, R. Perez and other members of the lab for technical help and support; O. Carreño, L. Damerius, N. Arnold, N. Meier and S. Peterhans for help with fly work; and K. Basler and R. Eisenman for critical comments on the manuscript. This work was financially supported by a grant from the Schweizerische Nationalfonds (SNF).

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Correspondence to Peter Gallant.

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Steiger, D., Furrer, M., Schwinkendorf, D. et al. Max-independent functions of Myc in Drosophila melanogaster. Nat Genet 40, 1084–1091 (2008). https://doi.org/10.1038/ng.178

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