Fig. 1

Structural mechanism of Trib2. Trib2 contains an N-terminal domain (PEST), a C-terminal E3 ligase-binding domain, a and pseudokinase domain with a Ser/Thr protein kinase-like domain. The C-terminal domain has the HPW [F/L] motif (targets MAPKK/MEK family members) and the conserved DQXVP [D/E] peptide motif (binds to COP1 E3 ubiquitin ligases). Trib2 can recruit the E3 ligase and induce degradation of CCAAT/enhancer-binding protein β (C/EBPβ). Trib2 regulates a wide range of key signaling pathways such as mitogen-activated protein kinase (MAPKs), nuclear factor-κB (NF-kB), protein kinase B (PKB or AKT), activating transcription factor 4 (ATF4), B-cell lymphoma 2 (BCL2), FOXO (forkhead box protein O), and activating enhancer-binding protein 4 (AP4)