Human FUBP1 was discovered over 25 years ago, as a single stranded DNA binding protein, and transcriptional activator of the MYC oncogene. In accordance, FUBP1 is upregulated in many cancers, including breast, liver, bladder, kidney, lung, prostate. Moreover, our recent Drosophila studies revealed the FUBP1 ortholog (dFUBP1/Psi) interacts with the transcriptional Mediator (MED) complex, to integrate developmental signals, activate MYC and promote cell and tissue growth in the wing epithelium. Paradoxically, our recent unpublished data demonstrate expansion of the glial lineage in loss-of-function dFUBP1 mutants, suggesting anti-proliferative capacity in the context of the brain. The developmental context-dependency of FUBP1 function is also clear from analysis of the Fubp1 knockout mice; while hypoproliferation is observed in the embryonic blood lineage, hypercellularity occurs in the brain.
FUBP1 loss-of-function ranks in the top 10% of predicted driver mutations in oligodendroglioma, the second most common primary brain cancer in adults. The anti-proliferative function of FUBP1 in the mouse and fly brain could provide a rationale for the otherwise inexplicable prediction that FUBP1 behaves as a tumour suppressor in glial lineage tumours. The prolonged survival time (around 15 years) of patients with these low grade, but invasive, brain tumours is associated with significant morbidity. Moreover, they typically recur following current treatments with unpredictable outcomes; some remain low grade while others become more aggressive. Thus, to improve patient outcomes we are currently using our genetic models to determine molecular mechanisms of FUBP1-dependent glial lineage overproliferation, toward development of new prognostic markers and potential drug targets.