POSH (Plenty of SH3): a novel genetic modifier of Myc function in Drosophila

Abstract: MYC is a conserved transcriptional regulator that coordinates cellular growth, metabolism, and tissue homeostasis through a broad network of downstream effectors. However, the signaling components that translate MYC activity into specific cellular responses remain incompletely defined. Here, using Drosophila melanogaster, we identify Plenty of SH3s (POSH), a conserved RING-domain scaffold protein and regulator of JNK signaling, as a novel genetic interactor of Myc. POSH was identified in a genetic screen for modifiers of a Myc-dependent phenotype in the developing eye. The interaction was independently confirmed using a UAS-Posh transgene. Quantitative analysis showed that reduced Myc primarily decreased ommatidial size, whereas POSH expression predominantly reduced ommatidial number, with this effect becoming more pronounced in Myc-sensitized backgrounds. Myc overexpression also increased Posh transcript levels, and the Posh regulatory region contains a canonical E-box motif, supporting a functional relationship between the two genes while leaving open the question of whether Posh is a direct Myc transcriptional target. Co-expression experiments further revealed a strong morphological interaction between Myc and POSH in the adult eye. Together, these findings identify POSH as a previously unrecognized genetic modifier of Myc function in Drosophila and provide a framework for investigating how Myc interfaces with stress-responsive signaling pathways during tissue development.