“…Unlike Lys48-linked polyubiquitination [36], which normally targets proteins for degradation by the proteasome, Lys63-linked polyubiquitin chains act as scaffolds for the assembly of protein complexes and mediate their activation through proteasome-independent mechanisms [37]. While Lys63-linked ubiquitination of Beclin-1 by the E3 ubiquitin ligase TRAF6 is crucial for TLR4-triggered autophagy in macrophages, the deubiquitinating enzyme A20 reduces the Lys63-linked ubiquitination of Beclin-1 and limits the induction of autophagy in response to TLR4 signaling [27]. Furthermore, treatment of macrophages with either interferon or interleukin-1 triggers the Lys63-linked ubiquitination of Beclin-1 and the formation of autophagosomes [27].…”