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Oxidative stress–induced assembly of PML nuclear bodies controls sumoylation of partner proteins

The promyelocytic leukemia (PML) protein organizes PML nuclear bodies (NBs), which are stress-responsive domains where many partner proteins accumulate. Here, we clarify the basis for NB formation and identify stress-induced partner sumoylation as the primary NB function. NB nucleation does not rely...

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Autores principales: Sahin, Umut, Ferhi, Omar, Jeanne, Marion, Benhenda, Shirine, Berthier, Caroline, Jollivet, Florence, Niwa-Kawakita, Michiko, Faklaris, Orestis, Setterblad, Niclas, de Thé, Hugues, Lallemand-Breitenbach, Valérie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998805/
https://www.ncbi.nlm.nih.gov/pubmed/24637324
http://dx.doi.org/10.1083/jcb.201305148
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author Sahin, Umut
Ferhi, Omar
Jeanne, Marion
Benhenda, Shirine
Berthier, Caroline
Jollivet, Florence
Niwa-Kawakita, Michiko
Faklaris, Orestis
Setterblad, Niclas
de Thé, Hugues
Lallemand-Breitenbach, Valérie
author_facet Sahin, Umut
Ferhi, Omar
Jeanne, Marion
Benhenda, Shirine
Berthier, Caroline
Jollivet, Florence
Niwa-Kawakita, Michiko
Faklaris, Orestis
Setterblad, Niclas
de Thé, Hugues
Lallemand-Breitenbach, Valérie
author_sort Sahin, Umut
collection PubMed
description The promyelocytic leukemia (PML) protein organizes PML nuclear bodies (NBs), which are stress-responsive domains where many partner proteins accumulate. Here, we clarify the basis for NB formation and identify stress-induced partner sumoylation as the primary NB function. NB nucleation does not rely primarily on intermolecular interactions between the PML SUMO-interacting motif (SIM) and SUMO, but instead results from oxidation-mediated PML multimerization. Oxidized PML spherical meshes recruit UBC9, which enhances PML sumoylation, allow partner recruitment through SIM interactions, and ultimately enhance partner sumoylation. Intermolecular SUMO–SIM interactions then enforce partner sequestration within the NB inner core. Accordingly, oxidative stress enhances NB formation and global sumoylation in vivo. Some NB-associated sumoylated partners also become polyubiquitinated by RNF4, precipitating their proteasomal degradation. As several partners are protein-modifying enzymes, NBs could act as sensors that facilitate and confer oxidative stress sensitivity not only to sumoylation but also to other post-translational modifications, thereby explaining alterations of stress response upon PML or NB loss.
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spelling pubmed-39988052014-09-17 Oxidative stress–induced assembly of PML nuclear bodies controls sumoylation of partner proteins Sahin, Umut Ferhi, Omar Jeanne, Marion Benhenda, Shirine Berthier, Caroline Jollivet, Florence Niwa-Kawakita, Michiko Faklaris, Orestis Setterblad, Niclas de Thé, Hugues Lallemand-Breitenbach, Valérie J Cell Biol Research Articles The promyelocytic leukemia (PML) protein organizes PML nuclear bodies (NBs), which are stress-responsive domains where many partner proteins accumulate. Here, we clarify the basis for NB formation and identify stress-induced partner sumoylation as the primary NB function. NB nucleation does not rely primarily on intermolecular interactions between the PML SUMO-interacting motif (SIM) and SUMO, but instead results from oxidation-mediated PML multimerization. Oxidized PML spherical meshes recruit UBC9, which enhances PML sumoylation, allow partner recruitment through SIM interactions, and ultimately enhance partner sumoylation. Intermolecular SUMO–SIM interactions then enforce partner sequestration within the NB inner core. Accordingly, oxidative stress enhances NB formation and global sumoylation in vivo. Some NB-associated sumoylated partners also become polyubiquitinated by RNF4, precipitating their proteasomal degradation. As several partners are protein-modifying enzymes, NBs could act as sensors that facilitate and confer oxidative stress sensitivity not only to sumoylation but also to other post-translational modifications, thereby explaining alterations of stress response upon PML or NB loss. The Rockefeller University Press 2014-03-17 /pmc/articles/PMC3998805/ /pubmed/24637324 http://dx.doi.org/10.1083/jcb.201305148 Text en © 2014 Sahin et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Sahin, Umut
Ferhi, Omar
Jeanne, Marion
Benhenda, Shirine
Berthier, Caroline
Jollivet, Florence
Niwa-Kawakita, Michiko
Faklaris, Orestis
Setterblad, Niclas
de Thé, Hugues
Lallemand-Breitenbach, Valérie
Oxidative stress–induced assembly of PML nuclear bodies controls sumoylation of partner proteins
title Oxidative stress–induced assembly of PML nuclear bodies controls sumoylation of partner proteins
title_full Oxidative stress–induced assembly of PML nuclear bodies controls sumoylation of partner proteins
title_fullStr Oxidative stress–induced assembly of PML nuclear bodies controls sumoylation of partner proteins
title_full_unstemmed Oxidative stress–induced assembly of PML nuclear bodies controls sumoylation of partner proteins
title_short Oxidative stress–induced assembly of PML nuclear bodies controls sumoylation of partner proteins
title_sort oxidative stress–induced assembly of pml nuclear bodies controls sumoylation of partner proteins
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998805/
https://www.ncbi.nlm.nih.gov/pubmed/24637324
http://dx.doi.org/10.1083/jcb.201305148
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