Evidence for a Nuclear Role for Drosophila Dlg as a Regulator of the NURF Complex

Scrib, Dlg, and Lgl are basolateral regulators of epithelial polarity and tumor suppressors whose molecular mechanisms of action remain unclear. We used proximity biotinylation to identify proteins localized near Dlg in the Drosophila wing imaginal disc epithelium. In addition to expected membrane- and cytoskeleton-associated protein classes, nuclear proteins were prevalent in the resulting mass spectrometry data set, including all four members of the NURF chromatin remodeling complex. Subcellular fractionation demonstrated a nuclear pool of Dlg and proximity ligation confirmed its position near the NURF complex. Genetic analysis showed that NURF activity is also required for the overgrowth of dlg tumors, and this growth suppression correlated with a reduction in Hippo pathway gene expression. Together, these data suggest a nuclear role for Dlg in regulating chromatin and transcription through a more direct mechanism than previously thought. Highlight SummaryProximity proteomics is used as an entry point towards identifying partners of the polarity-regulating tumor suppressor Dlg. A nuclear pool of the protein associated with NURF chromatin remodelers is revealed, along with evidence of functional interactions during growth regulation.