Fig. 4.

EXT1 depletion promotes NOTCH1 transcriptional activity. a Interactions between NOTCH1, EXT1 and FBXW7. Grey nodes represent proteins associated with ALL, with an area proportional to the number of distinct mutations. Bleu edges join pairs of interacting proteins for which mutations co-occur in the same samples. Edge widths are proportional to the number of samples with co-occurring mutations. The green node represent EXT1 and grey edges interactions identified in Y2H (b) Luciferase reporter assay using TP1-luciferase construct in HeLa Notch∆E-eGFP cell lines transfected with EXT1 siRNA or control siRNA as indicated. The relative luciferase values are normalized using a Renilla luciferase construct. Knock-down of EXT1 was analysed by qPCR. c mRNA expression levels of Notch1 target genes; cMYC and EXT1 analysed by qPCR following EXT1 Knock down. d A zebrafish transgenic line Tg (Tp1bglob:eGFP) um13, reporter for Notch1 transcriptional activity, were treated with control or Ext1 a and c ortholog-targeted morpholinos. Left panel represents TP1 bglob:hngb1-eGFP construct. The graph represents the percentage eGFP cells sorted by FACS. Data represent the means ± SEs of three independent experiments