Figure 7. p90RSK regulates ERK5-CHIP module.

(A) A model of myocardial infarction under diabetes (DM + MI) or angiotensin II (Ang II)-mediated p90RSK-ERK5-CHIP signal transduction pathway that regulates cardiac apoptosis and subsequent cardiac dysfunction. (B) A scheme depicting p90RSK-mediated regulation of the ERK5-CHIP module. At the basal level, inactive p90RSK inhibits the D-domain to bind with ERK5(Gao et al., 2010). p90RSK-free ERK5 associates with CHIP at its linker and U-box domain and maintains its CHIP Ub ligase activity to prevent ICER induction and subsequent apoptosis¹³. However, once p90RSK gets activated, the inhibition of the kinase domain is released(Gao et al., 2010, Woo et al., 2010), and the D-domain of p90RSK associates with the ERK5 COOH-terminal domain, leading to compete with ERK5-CHIP association and ERK5-S496 phosphorylation, which disrupts ERK5-CHIP interaction. The disruption of ERK5-CHIP interaction inhibits CHIP Ub ligase activity(Woo et al., 2010), increases ICER induction, and induces apoptosis(Woo et al., 2010, Esser et al., 2005). Reprinted from Le et al(Le et al., 2012) with permission of the publisher.