title: Oxidative stress-induced assembly of PML nuclear bodies controls sumoylation of partner proteins.
abstract: 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.
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, Hôpital St. Louis 1, 75475 Paris Cedex 10, France.
authors.forename: Umut
authors.initials: U
authors.lastname: Sahin
authors.forename: Omar
authors.initials: O
authors.lastname: Ferhi
authors.forename: Marion
authors.initials: M
authors.lastname: Jeanne
authors.forename: Shirine
authors.initials: S
authors.lastname: Benhenda
authors.forename: Caroline
authors.initials: C
authors.lastname: Berthier
authors.forename: Florence
authors.initials: F
authors.lastname: Jollivet
authors.forename: Michiko
authors.initials: M
authors.lastname: Niwa-Kawakita
authors.forename: Orestis
authors.initials: O
authors.lastname: Faklaris
authors.forename: Niclas
authors.initials: N
authors.lastname: Setterblad
authors.forename: Hugues
authors.initials: H
authors.lastname: de Thé
authors.forename: Valérie
authors.initials: V
authors.lastname: Lallemand-Breitenbach
mesh_terms: D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism; D016922:Cellular Senescence; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D018384:Oxidative Stress; D000071156:Promyelocytic Leukemia Protein; D021381:Protein Transport; D017382:Reactive Oxygen Species / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D058207:Sumoylation; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D009687:Nuclear Proteins; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D017382:Reactive Oxygen Species; D025841:Small Ubiquitin-Related Modifier Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D044763:Ubiquitin-Conjugating Enzymes; C486410:Rnf4 protein, mouse; D044767:Ubiquitin-Protein Ligases; D000098843:Ubiquitin-Conjugating Enzyme UBC9