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Schematic working model for ER stress/ERK1/2-mediated signalling of BH3 mimetics (e.g. S1)-induced Bcl-2 expression and phosphorylation. BH3 mimetics, such as S1 and ABT-737, stimulate ER stress then induce MAPK/ERK cascades with respect to Bcl-2 transcriptional up-regulation (solid arrowhead) and phosphorylation (hollow arrowhead). Excess pBcl-2 leads to cell survival by promoting ERK1/2 activation and sequestrating more pro-apoptotic members, which BH3 mimetics cannot release.
