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PreprintCC BY-NC-NDbioRxiv

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

  1. 1University of Trento

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.

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BibTeX
@misc{kuo2026posh,
  title = {{POSH (Plenty of SH3): a novel genetic modifier of Myc function in Drosophila}},
  author = {V. Kuo and M. Daniel and S. Zola and P. Bellosta},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.19.760028},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.19.760028v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - POSH (Plenty of SH3): a novel genetic modifier of Myc function in Drosophila
AU  - V. Kuo
AU  - M. Daniel
AU  - S. Zola
AU  - P. Bellosta
PY  - 2026
DA  - 2026/10/19
PB  - bioRxiv
DO  - 10.64898/2026.10.19.760028
UR  - https://www.biorxiv.org/content/10.64898/2026.10.19.760028v1
AB  - 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.
ER  -