ISG15 modification of Ubc13 suppresses its ubiquitin-conjugating activity.
ISG15 is one of the interferon-stimulated genes and is classified as a ubiquitin-like protein. Upon interferon stimuli, ISG15 is upregulated and becomes conjugated to various cellular proteins (ISGylation). Several target proteins for ISGylation have recently been identified, but the biological consequence of protein ISGylation remains unclear. In the course of our study to identify components of the ISGylation system, we found that Ubc13, an E2 enzyme for ubiquitin conjugation, is covalently modified with ISG15. To determine the meaning of ISGylation of Ubc13, we isolated ISG15-modified Ubc13 protein and compared its ubiquitin-conjugating activity with that of an unmodified one. We found that ISGylation of Ubc13 suppresses its ability to form a thioester intermediate with ubiquitin.
Takeuchi
Tomoharu
T
Department of Biochemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Yokosawa
Hideyoshi
H
D016207:Cytokines / Q000737:chemistry*; D006801:Humans; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D014452:Ubiquitins / Q000737:chemistry
D016207:Cytokines; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D014452:Ubiquitins; C074034:ISG15 protein, human; C471610:UBC13 protein, S cerevisiae; D044763:Ubiquitin-Conjugating Enzymes