Multiubiquitylation by E4 enzymes: 'one size' doesn't fit all.
Selective protein degradation by the 26S proteasome requires the covalent attachment of several ubiquitin molecules in the form of a multiubiquitin chain. Ubiquitylation usually involves three classes of enzymes: a ubiquitin-activating enzyme (E1), a ubiquitin-conjugating enzyme (E2) and a ubiquitin ligase (E3). However, in some cases, multiubiquitylation requires the additional activity of certain ubiquitin-chain elongation factors. Yeast UFD2 (ubiquitin fusion degradation), for example, binds to oligoubiquitylated substrates (proteins modified by only a few ubiquitin molecules) and catalyses multiubiquitin-chain assembly in collaboration with E1, E2 and E3. Enzymes possessing this specific activity have been proposed to be termed 'E4 enzymes'. Recent studies have provided accumulating evidence that has led some researchers in the field to conclude that E4, indeed, represents a distinct and novel class of enzymes.
Hoppe
Thorsten
T
Centre for Molecular Neurobiology (ZMNH), University of Hamburg, Falkenried 94, 20251 Hamburg, Germany. thorsten.hoppe@zmnh.uni-hamburg.de
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D006801:Humans; D009097:Multienzyme Complexes; D025821:Polyubiquitin / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C099939:BUL1 protein, S cerevisiae; D029742:Caenorhabditis elegans Proteins; D009097:Multienzyme Complexes; D029701:Saccharomyces cerevisiae Proteins; D025821:Polyubiquitin; D044763:Ubiquitin-Conjugating Enzymes; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; C487100:chn-1 protein, C elegans; C114683:UFD2 protein, S cerevisiae