title: Promyelocytic Leukemia Protein, a Protein at the Crossroad of Oxidative Stress and Metabolism.
abstract: Cellular metabolic activity impacts the production of reactive oxygen species (ROS), both positively through mitochondrial oxidative processes and negatively by promoting the production of reducing agents (including NADPH and reduced glutathione). A defined metabolic state in cancer cells is critical for cell growth and long-term self-renewal, and such state is intrinsically associated with redox balance. Promyelocytic leukemia protein (PML) regulates several biological processes, at least in part, through its ability to control the assembly of PML nuclear bodies (PML NBs). Recent Advances: PML is oxidation-prone, and oxidative stress promotes NB biogenesis. These nuclear subdomains recruit many nuclear proteins and regulate their SUMOylation and other post-translational modifications. Some of these cargos-such as p53, SIRT1, AKT, and mammalian target of rapamycin (mTOR)-are key regulators of cell fate. PML was also recently shown to regulate oxidation.
  
  
  
  While it was long considered primarily as a tumor suppressor protein, PML-regulated metabolic switch uncovered that this protein could promote survival and/or stemness of some normal or cancer cells. In this study, we review the recent findings on this multifunctional protein.
  
  
  
  Studying PML scaffolding functions as well as its fine role in the activation of p53 or fatty acid oxidation will bring new insights in how PML could bridge oxidative stress, senescence, cell death, and metabolism. Antioxid. Redox Signal. 26, 432-444.
authors.affiliation: 1 Collège de France , Paris, France .|2 INSERM UMR 944, Equipe labellisée par la Ligue Nationale contre le Cancer, Institut Universitaire d'Hématologie , Paris, France .|3 CNRS UMR 7212 , Paris France .|4 Université Paris Diderot-Sorbonne Paris Cité , Paris, France .
authors.forename: Sarah
authors.initials: S
authors.lastname: Tessier
authors.affiliation: 5 CIC bioGUNE , Bizkaia Technology Part, Derio, Spain .
authors.forename: Natalia
authors.initials: N
authors.lastname: Martin-Martin
authors.affiliation: 1 Collège de France , Paris, France .|2 INSERM UMR 944, Equipe labellisée par la Ligue Nationale contre le Cancer, Institut Universitaire d'Hématologie , Paris, France .|3 CNRS UMR 7212 , Paris France .|4 Université Paris Diderot-Sorbonne Paris Cité , Paris, France .|6 AP-HP, Service de Biochimie, Hôpital St. Louis , Paris, France .
authors.forename: Hugues
authors.initials: H
authors.lastname: de Thé
authors.affiliation: 5 CIC bioGUNE , Bizkaia Technology Part, Derio, Spain .|7 IKERBASQUE , Basque Foundation for Science, Bilbao, Spain .|8 Biochemistry and Molecular Biology Department, University of the Basque Country (UPV/EHU) , Bilbao, Spain .
authors.forename: Arkaitz
authors.initials: A
authors.lastname: Carracedo
authors.affiliation: 1 Collège de France , Paris, France .|2 INSERM UMR 944, Equipe labellisée par la Ligue Nationale contre le Cancer, Institut Universitaire d'Hématologie , Paris, France .|3 CNRS UMR 7212 , Paris France .|4 Université Paris Diderot-Sorbonne Paris Cité , Paris, France .
authors.forename: Valérie
authors.initials: V
authors.lastname: Lallemand-Breitenbach
mesh_terms: D000818:Animals; D001343:Autophagy; D004734:Energy Metabolism; D006801:Humans; D045586:Intranuclear Inclusion Bodies / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D000071156:Promyelocytic Leukemia Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D058207:Sumoylation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53
keywords: PML nuclear bodies; cancer; fatty acid metabolism; oxidative stress