UBR2 and neoplasm: UBR2 is the only known N-end rule pathway E3 that is upregulated by cachectic stimuli including tumor and pro-inflammatory cytokines (TNFα and IL-6), and is highly efficient for protein ubiquitylation via the N-end rule pathway [75], which makes it a potential candidate E3 that mediates myofibrillar protein loss through the UPP.