Proper control of cell size is vital to ensure the correct growth and development of any organism. The Myc family of proteins are key regulators of growth, but the mechanisms that control Myc protein levels are complex. Now, on , Robert Eisenman and colleagues identify Drosophila Puffyeye (Puf), an orthologue of mammalian USP34, as a novel ubiquitin-specific protease (USP) regulating dMyc-dependant cell growth at the post-translational level. Using genetic interaction experiments, the authors demonstrate that puf opposes the activity of the ubiquitin ligase archipelago (ago) and that Puf acts to stabilise dMyc protein levels. Overexpression of puf in the eye and wing phenocopies dMyc overexpression, while expression of a catalytically inactive form of Puf had no effect, demonstrating the requirement of the Puf USP catalytic domain. Interestingly, the authors demonstrated that Puf can also regulate Ago and Cyclin E protein levels. These data reveal a new mechanism by which dMyc levels can be regulated by USPs in order to fine-tune cell growth.
