NRF2 Regulates HER2 and HER3 Signaling Pathway to Modulate Sensitivity to Targeted Immunotherapies

Figure 8

In silico analysis of HER2 and HER3 promoter sequences. (a) 1.5 kb promoter region of HER2 gene was fetched from database (ensemble.org) and subjected to transcriptional factor binding prediction program (http://consite.genereg.net/) to predict for putative NRF2 binding sites as indicated. Line with arrowheads shows the 0.7 kb sequence of HER2 promoter [8], while regions enclosed in rectangles show additional sequences included and cloned in the PGL3 luciferase reporter vector (Promega) because of carrying additional NRF2 binding sites. (b) The same analyses were performed for HER3 promoter. In (a) and (b), +1 indicate the transcriptional start site, sequences highlighted in green show NRF2 binding sites as predicted by ConSite, and sequences in bold represent manual identification of putative NRF2 binding sites based on ARE consensus sequence [9] while those highlighted in pink show overlapping NRF2 binding sites by the two methods mentioned above.

(a) Putative transcription factor binding sites found along HER2 promoter

(b) Putative transcription factor binding sites found along HER3 promoter