However, the lack of XBP1 splicing in Salmonella-infected cells (Supplementary Fig. 4c, d), as well as the observation that the inhibition of IRE1 endonuclease activity, using the 4μ8C inhibitor52, did not affect the extent of E2F1 downregulation observed upon Salmonella infection or by treatment with the secretome of Salmonella-infected cells (Supplementary Fig. 4i, j) led us to hypothesize that IRE1 could act through a mechanism independent of its endonuclease activity. The gene discussed is E2F1; the disease is Salmonella Infections.