Fig. 1

Vital signaling pathways and important substrates for downstream regulation of USP4. In Wnt/β-catenin signaling pathway, USP4 can stabilize β-catenin by deubiquitinating its K48-ubiquitin and inactivate Dvl and TCF4 by deubiquitinating their K63-ubiquitin. In TGF-β signaling pathway, USP4 can stabilize TβRI by deubiquitinating its K48-ubiquitin and deubiquitinate SMAD4 mono-ubiquitination. USP4 can inactivate TAK1, TRAF2 and TRAF6 and stabilize HDAC2 to inhibit NF-κB signaling pathway. Also, USP4 can stabilize TRAF6 to activate NF-κB signaling pathway. In p53-related signaling pathway, USP4 can stabilize ARF-BP1 and HDAC2 by deubiquitinating its K48-ubiquitin to promote the ubiquitination and degradation of p53