POSH (Plenty of SH3): A Novel Genetic Modifier of Myc Function in Drosophila

Background/Objectives: 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. This study aimed to identify novel genetic modifiers of Myc function in Drosophila melanogaster. Methods: A genetic screen was performed to identify modifiers of a Myc-dependent phenotype in the developing eye. The interaction was independently validated using a UAS-Posh transgene, followed by quantitative analysis of ommatidial size and number, co-expression experiments, and analysis of Posh transcript levels. Results: Plenty of SH3s (POSH), a conserved RING-domain scaffold protein involved in JNK signaling, was identified as a novel genetic interactor of Myc. Reduced Myc activity primarily decreased ommatidial size, whereas POSH expression predominantly reduced ommatidial number, with this effect becoming more pronounced in Myc-sensitized backgrounds. Co-expression of Myc and POSH produced marked alterations in adult eye morphology. Myc overexpression also increased Posh transcript levels, and a canonical E-box motif was identified in the posh regulatory region, suggesting a potential transcriptional relationship between the two genes. Conclusions: These findings identify POSH as a previously unrecognized genetic modifier of Myc function in Drosophila. Although direct transcriptional regulation and the underlying molecular mechanisms remain to be established, the results provide a basis for investigating the relationship between Myc-dependent growth and stress-responsive signaling pathways during tissue development.