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How the ends signal the end: Regulation by E3 ubiquitin ligases recognizing protein termini

Specificity of eukaryotic protein degradation is determined by E3 ubiquitin ligases and their selective binding to protein motifs, termed “degrons,” in substrates for ubiquitin-mediated proteolysis. From the discovery of the first substrate degron and the corresponding E3 to a flurry of recent studi...

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Detalles Bibliográficos
Autores principales: Sherpa, Dawafuti, Chrustowicz, Jakub, Schulman, Brenda A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9098119/
https://www.ncbi.nlm.nih.gov/pubmed/35247307
http://dx.doi.org/10.1016/j.molcel.2022.02.004
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author Sherpa, Dawafuti
Chrustowicz, Jakub
Schulman, Brenda A.
author_facet Sherpa, Dawafuti
Chrustowicz, Jakub
Schulman, Brenda A.
author_sort Sherpa, Dawafuti
collection PubMed
description Specificity of eukaryotic protein degradation is determined by E3 ubiquitin ligases and their selective binding to protein motifs, termed “degrons,” in substrates for ubiquitin-mediated proteolysis. From the discovery of the first substrate degron and the corresponding E3 to a flurry of recent studies enabled by modern systems and structural methods, it is clear that many regulatory pathways depend on E3s recognizing protein termini. Here, we review the structural basis for recognition of protein termini by E3s and how this recognition underlies biological regulation. Diverse E3s evolved to harness a substrate's N and/or C terminus (and often adjacent residues as well) in a sequence-specific manner. Regulation is achieved through selective activation of E3s and also through generation of degrons at ribosomes or by posttranslational means. Collectively, many E3 interactions with protein N and C termini enable intricate control of protein quality and responses to cellular signals.
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spelling pubmed-90981192022-06-14 How the ends signal the end: Regulation by E3 ubiquitin ligases recognizing protein termini Sherpa, Dawafuti Chrustowicz, Jakub Schulman, Brenda A. Mol Cell Review Specificity of eukaryotic protein degradation is determined by E3 ubiquitin ligases and their selective binding to protein motifs, termed “degrons,” in substrates for ubiquitin-mediated proteolysis. From the discovery of the first substrate degron and the corresponding E3 to a flurry of recent studies enabled by modern systems and structural methods, it is clear that many regulatory pathways depend on E3s recognizing protein termini. Here, we review the structural basis for recognition of protein termini by E3s and how this recognition underlies biological regulation. Diverse E3s evolved to harness a substrate's N and/or C terminus (and often adjacent residues as well) in a sequence-specific manner. Regulation is achieved through selective activation of E3s and also through generation of degrons at ribosomes or by posttranslational means. Collectively, many E3 interactions with protein N and C termini enable intricate control of protein quality and responses to cellular signals. Cell Press 2022-04-21 /pmc/articles/PMC9098119/ /pubmed/35247307 http://dx.doi.org/10.1016/j.molcel.2022.02.004 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Review
Sherpa, Dawafuti
Chrustowicz, Jakub
Schulman, Brenda A.
How the ends signal the end: Regulation by E3 ubiquitin ligases recognizing protein termini
title How the ends signal the end: Regulation by E3 ubiquitin ligases recognizing protein termini
title_full How the ends signal the end: Regulation by E3 ubiquitin ligases recognizing protein termini
title_fullStr How the ends signal the end: Regulation by E3 ubiquitin ligases recognizing protein termini
title_full_unstemmed How the ends signal the end: Regulation by E3 ubiquitin ligases recognizing protein termini
title_short How the ends signal the end: Regulation by E3 ubiquitin ligases recognizing protein termini
title_sort how the ends signal the end: regulation by e3 ubiquitin ligases recognizing protein termini
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9098119/
https://www.ncbi.nlm.nih.gov/pubmed/35247307
http://dx.doi.org/10.1016/j.molcel.2022.02.004
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