Fbxw5 suppresses nuclear c-Myb activity via DDB1-Cul4-Rbx1 ligase-mediated sumoylation

► Fbxw5 enhances sumoylation of c-Myb. ► The DDB1-Cul4A-Rbx1 complex mediates c-Myb sumoylation. ► The Fbxw5-DDB1-Cul4A-Rdx1 complex is a dual SUMO/ubiquitin ligase. ► Fbxw5 suppresses the c-Myb trans-activating capacity.