Finally, although we clearly demonstrated that ROS-triggered TRAF6 ubiquitination and the followed activation of TAK1-JNK1/2/p38 signalling are responsible for TRAF6-regulated cardiac hypertrophy, the gap of how post-translational modifications of TRAF6 lead to activation of the E3 ligase needs to be further filled. Here, MAPK8 is linked to cardiac hypertrophy.