Signalling pathways controlling transcription of the myc oncogene and cell overgrowth in Drosophila via Psi. Amanda Jue Er Lee¹, Nicola Cranna¹, Naomi Mitchell¹, David Levens³, Ross Hannan², Leonie Quinn¹. 1) Anatomy and Neuroscience, University of Melbourne, Parkville, VIC, Australia; 2) Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; 3) National Cancer Institute, Bethesda, Maryland, United States.

   Myc proteins are critical regulators of growth and cell cycle progression during animal development. Dysregulation of Myc can result in over proliferation and malignant transformation. In addition, Myc transcription must rapidly respond to environmental cues, which feed into developmental signalling pathways. In vitro studies in mammals have demonstrated activated expression of the c-Myc oncogene in response to growth factors in serum, which correlates with recruitment of the single-stranded DNA binding protein FBP, but the signals promoting recruitment of FPB to activated c-Myc are currently unknown. In an effort to better understand activation and repression of Myc transcription in an in vivo signalling environment, we have developed models to study the Drosophila orthologs of FPB and FIR, Psi and Hfp respectively. Our work has previously shown that Hfp is also a critical dMyc repressor, and we will present evidence that Psi is required for activated dMyc transcription. In addition, we have provided the first evidence that Ras pathway activation increases the abundance of dMyc via transcriptional effects. Furthermore, we demonstrate that dMyc upregulation and cell growth observed upon activation of the Ras pathway is dependent on Psi. Together the data we will present demonstrate that Psi may provide an important link between the Ras signalling pathway, dMyc promoter activity, cell growth and cell cycle progression.