OTUB1 non-catalytically stabilizes the E2 ubiquitin-conjugating enzyme UBE2E1 by preventing its autoubiquitination
| العنوان: | OTUB1 non-catalytically stabilizes the E2 ubiquitin-conjugating enzyme UBE2E1 by preventing its autoubiquitination |
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| المؤلفون: | Cynthia Wolberger, Barbara A. Malynn, Lauren T. Que, Nagesh Pasupala, Marie E. Morrow, Averil Ma |
| المصدر: | The Journal of Biological Chemistry |
| بيانات النشر: | American Society for Biochemistry and Molecular Biology, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, ubiquitin-conjugating enzyme (E2 enzyme), Amino Acid Motifs, histone, UBE2E1, Ubiquitin-conjugating enzyme, Biochemistry, Deubiquitinating enzyme, 03 medical and health sciences, Mice, Ubiquitin, Animals, Molecular Biology, chemistry.chemical_classification, biology, Deubiquitinating Enzymes, Protein Stability, Ubiquitination, Cell Biology, Cell biology, Mice, Inbred C57BL, Cysteine Endopeptidases, 030104 developmental biology, Histone, Enzyme, deubiquitylation (deubiquitination), chemistry, Proteasome, OTUB1, Protein Synthesis and Degradation, Knockout mouse, Ubiquitin-Conjugating Enzymes, biology.protein, ubiquitin thioesterase (OTUB1), Protein Binding |
| الوصف: | OTUB1 is a deubiquitinating enzyme that cleaves Lys-48–linked polyubiquitin chains and also regulates ubiquitin signaling through a unique, noncatalytic mechanism. OTUB1 binds to a subset of E2 ubiquitin-conjugating enzymes and inhibits their activity by trapping the E2∼ubiquitin thioester and preventing ubiquitin transfer. The same set of E2s stimulate the deubiquitinating activity of OTUB1 when the E2 is not charged with ubiquitin. Previous studies have shown that, in cells, OTUB1 binds to E2-conjugating enzymes of the UBE2D (UBCH5) and UBE2E families, as well as to UBE2N (UBC13). Cellular roles have been identified for the interaction of OTUB1 with UBE2N and members of the UBE2D family, but not for interactions with UBE2E E2 enzymes. We report here a novel role for OTUB1–E2 interactions in modulating E2 protein ubiquitination. We observe that Otub1−/− knockout mice exhibit late-stage embryonic lethality. We find that OTUB1 depletion dramatically destabilizes the E2-conjugating enzyme UBE2E1 (UBCH6) in both mouse and human OTUB1 knockout cell lines. Of note, this effect is independent of the catalytic activity of OTUB1, but depends on its ability to bind to UBE2E1. We show that OTUB1 suppresses UBE2E1 autoubiquitination in vitro and in cells, thereby preventing UBE2E1 from being targeted to the proteasome for degradation. Taken together, we provide evidence that OTUB1 rescues UBE2E1 from degradation in vivo. |
| اللغة: | English |
| تدمد: | 1083-351X 0021-9258 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::91ca0691829e765000c49deb66415c1e http://europepmc.org/articles/PMC6254341 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....91ca0691829e765000c49deb66415c1e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1083351X 00219258 |
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