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Ubiquitin chain-elongating enzyme UBE2S activates the RING E3 ligase APC/C for substrate priming
The interplay between E2 and E3 enzymes regulates the polyubiquitination of substrates in eukaryotes. Among the several RING-domain E3 ligases in humans, many utilize two distinct E2s for polyubiquitination. For example, the cell cycle regulatory E3, human Anaphase-Promoting Complex/Cyclosome (APC/C...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293561/ https://www.ncbi.nlm.nih.gov/pubmed/32393902 http://dx.doi.org/10.1038/s41594-020-0424-6 |
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author | Martinez-Chacin, Raquel C. Bodrug, Tatyana Bolhuis, Derek L. Kedziora, Katarzyna M. Bonacci, Thomas Ordureau, Alban Gibbs, Morgan E. Weissmann, Florian Qiao, Renping Grant, Gavin D. Cook, Jeanette G. Peters, Jan-Michael Harper, J. Wade Emanuele, Michael J. Brown, Nicholas G. |
author_facet | Martinez-Chacin, Raquel C. Bodrug, Tatyana Bolhuis, Derek L. Kedziora, Katarzyna M. Bonacci, Thomas Ordureau, Alban Gibbs, Morgan E. Weissmann, Florian Qiao, Renping Grant, Gavin D. Cook, Jeanette G. Peters, Jan-Michael Harper, J. Wade Emanuele, Michael J. Brown, Nicholas G. |
author_sort | Martinez-Chacin, Raquel C. |
collection | PubMed |
description | The interplay between E2 and E3 enzymes regulates the polyubiquitination of substrates in eukaryotes. Among the several RING-domain E3 ligases in humans, many utilize two distinct E2s for polyubiquitination. For example, the cell cycle regulatory E3, human Anaphase-Promoting Complex/Cyclosome (APC/C), relies on UBE2C to prime substrates with ubiquitin (Ub) and UBE2S to extend polyubiquitin chains. However, the potential coordination between these steps in ubiquitin chain formation remains undefined. While numerous studies have unveiled how RING E3s stimulate individual E2s for Ub transfer, here we change perspective to describe a case where the chain-elongating E2 UBE2S feeds back and directly stimulates the E3 APC/C to promote substrate priming and subsequent multiubiquitination by UBE2C. Our work reveals an unexpected paradigm for the mechanisms of RING E3-dependent ubiquitination and for the diverse and complex interrelationship between components of the ubiquitination cascade. |
format | Online Article Text |
id | pubmed-7293561 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
record_format | MEDLINE/PubMed |
spelling | pubmed-72935612020-11-11 Ubiquitin chain-elongating enzyme UBE2S activates the RING E3 ligase APC/C for substrate priming Martinez-Chacin, Raquel C. Bodrug, Tatyana Bolhuis, Derek L. Kedziora, Katarzyna M. Bonacci, Thomas Ordureau, Alban Gibbs, Morgan E. Weissmann, Florian Qiao, Renping Grant, Gavin D. Cook, Jeanette G. Peters, Jan-Michael Harper, J. Wade Emanuele, Michael J. Brown, Nicholas G. Nat Struct Mol Biol Article The interplay between E2 and E3 enzymes regulates the polyubiquitination of substrates in eukaryotes. Among the several RING-domain E3 ligases in humans, many utilize two distinct E2s for polyubiquitination. For example, the cell cycle regulatory E3, human Anaphase-Promoting Complex/Cyclosome (APC/C), relies on UBE2C to prime substrates with ubiquitin (Ub) and UBE2S to extend polyubiquitin chains. However, the potential coordination between these steps in ubiquitin chain formation remains undefined. While numerous studies have unveiled how RING E3s stimulate individual E2s for Ub transfer, here we change perspective to describe a case where the chain-elongating E2 UBE2S feeds back and directly stimulates the E3 APC/C to promote substrate priming and subsequent multiubiquitination by UBE2C. Our work reveals an unexpected paradigm for the mechanisms of RING E3-dependent ubiquitination and for the diverse and complex interrelationship between components of the ubiquitination cascade. 2020-05-11 2020-06 /pmc/articles/PMC7293561/ /pubmed/32393902 http://dx.doi.org/10.1038/s41594-020-0424-6 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Martinez-Chacin, Raquel C. Bodrug, Tatyana Bolhuis, Derek L. Kedziora, Katarzyna M. Bonacci, Thomas Ordureau, Alban Gibbs, Morgan E. Weissmann, Florian Qiao, Renping Grant, Gavin D. Cook, Jeanette G. Peters, Jan-Michael Harper, J. Wade Emanuele, Michael J. Brown, Nicholas G. Ubiquitin chain-elongating enzyme UBE2S activates the RING E3 ligase APC/C for substrate priming |
title | Ubiquitin chain-elongating enzyme UBE2S activates the RING E3 ligase APC/C for substrate priming |
title_full | Ubiquitin chain-elongating enzyme UBE2S activates the RING E3 ligase APC/C for substrate priming |
title_fullStr | Ubiquitin chain-elongating enzyme UBE2S activates the RING E3 ligase APC/C for substrate priming |
title_full_unstemmed | Ubiquitin chain-elongating enzyme UBE2S activates the RING E3 ligase APC/C for substrate priming |
title_short | Ubiquitin chain-elongating enzyme UBE2S activates the RING E3 ligase APC/C for substrate priming |
title_sort | ubiquitin chain-elongating enzyme ube2s activates the ring e3 ligase apc/c for substrate priming |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293561/ https://www.ncbi.nlm.nih.gov/pubmed/32393902 http://dx.doi.org/10.1038/s41594-020-0424-6 |
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