FIGURE 7.

Schematic working model for ERK/RSK-mediated signaling of drug (e.g. celecoxib)-induced DR5 expression through co-activation of both CHOP and Elk1. The data in the present study suggest that ERK1/2 activation can result in CHOP expression through RSK2-mediated ATF4 activation, which concurrently activates Elk1 through direct phosphorylation. It is also possible that activated RSK2 may enhance Elk1-mediated DR5 transactivation through direct interaction with Elk1. CHOP and Elk1 then co-operate to transactivate the DR5 gene and expression.