Ubiquitination by E3 ligases regulates diverse areas such as cell trafficking, DNA repair, and signaling and is of profound importance in cell biology. E3 ligases are also key players in cell cycle control, mediating the degradation of cyclins, as …

E3 ligases are critical for modulating cellular homeostasis owning to their efficient regulation and substrate specificity during the cascade of ubiquitination.

2021年7月30日 · E3 ubiquitin ligases play an essential role in catalyzing the ubiquitination process and transferring ubiquitin protein to attach the lysine site of targeted substrates. Importantly, ubiquitination modification is involved in almost all life activities of eukaryotes.

2017年6月20日 · Ubiquitin E3 ligases control every aspect of eukaryotic biology by promoting protein ubiquitination and degradation. At the end of a three-enzyme cascade, ubiquitin ligases mediate the transfer of ubiquitin from an E2 ubiquitin-conjugating enzyme to …

Here, we briefly review how traditional E3 ligase ligands were discovered, and then outline approaches and ligands that have been recently used to discover new E3 ligases for PROTACs.

The E3 ligases of the HECT (homologous to the E6AP carboxyl terminus) domain family catalyze ubiquitin transfer to the substrate protein through a two-step reaction: ubiquitin is first transferred to a catalytic cysteine on the E3 and then from the E3 to the substrate.

2024年12月17日 · Recruitment by an E3 ligase is a mandatory step in PROTACs and molecular glues mechanism of action. E3 ligases have diverse temporal, spatial and disease-related expression profiles and these differences can be exploited to …

2014年4月4日 · Three distinct classes of E3 ligases have been identified that stimulate transfer of ubiquitin and ubiquitin-like proteins through either a direct or an indirect mechanism. Only...

2016年8月3日 · Ubiquitin ligases (E3s) recruit ubiquitin-conjugating enzyme (E2) ∼ ubiquitin (∼ denotes a thioester linkage; here, the linkage is between the catalytic cysteine of E2 and the carboxyl terminus...

E3 Ub-ligases recognize structural motifs in the target, bind the substrate protein, and catalyze the formation of an amide isopeptide linkage between Gly 76 in the C-terminus of the Ub molecule (brought to the E3 by the E2) and the ε-amino group of a lysine residue in the target protein.