Fig. 1.

Ubiquitin-dependent and independent molecular mechanisms of protein degradation. a Ubiquitin conjugation system consists of ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin ligase (E3). Deubiquitylating enzymes (DUB) can remove ubiquitin chains from substrates. b Ubiquitin modification can be categorized as monoubiquitination, polyubiquitination, and branched ubiquitination, where Lys48 and Lys63 polyubiquitination chains are closely related to protein degradation. c The biological functions of substrates, including signaling transduction, protein conformation change, chromatin remodeling, proteasomal degradation, and lysosomal degradation, are further determined by the ubiquitin receptors. d Ubiquitin-independent targeted protein degradation includes 20S proteasome-mediated protein degradation and chaperone-mediated autophagy