Are Fusion Oncoproteins a Source of Disease-Relevant, Phase Separation-Prone Protein Regions?

Fusion oncoproteins (FOs) that originate from gene translocation are drivers of poor prognosis cancers in children. These FOs often include intrinsically disordered regions (IDRs) from transcription factors known to form transcriptional condensates through liquid-liquid phase separation (LLPS). We and others have demonstrated that the AML-driving NUP98 FOs form aberrant transcriptional condensates that alter gene expression and transform cells. We hypothesize that many FOs retain LLPS-prone IDRs from their parents that are a rich source of novel, disease-relevant LLPS-prone protein regions.