Interferon controls SUMO availability via the Lin28 and let-7 axis to impede virus replication

Autor: Umut Sahin, Omar Ferhi, Xavier Carnec, Alessia Zamborlini, Laurent Peres, Florence Jollivet, Adeline Vitaliano-Prunier, Hugues de Thé, Valérie Lallemand-Breitenbach
Přispěvatelé: Pathologie cellulaire : aspects moléculaires et viraux / Pathologie et Virologie Moléculaire, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Biochimie [AP-HP Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Lallemand-Breitenbach, Valérie
Jazyk: angličtina
Rok vydání: 2014
Předmět:
SUMO-1 Protein
SUMO protein
General Physics and Astronomy
HIV Infections
[SDV.CAN]Life Sciences [q-bio]/Cancer
SUMO2
Herpesvirus 1
Human
[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
Biology
LIN28
Virus Replication
General Biochemistry
Genetics and Molecular Biology
[SDV.CAN] Life Sciences [q-bio]/Cancer
Interferon
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Genomics [q-bio.GN]
microRNA
medicine
[SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
Humans
Ubiquitins
Genetics
Multidisciplinary
RNA-Binding Proteins
Herpes Simplex
General Chemistry
Cell biology
Haematopoiesis
MicroRNAs
Viral replication
HIV-1
Small Ubiquitin-Related Modifier Proteins
[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry
Molecular Biology/Genomics [q-bio.GN]
Interferons
Stem cell
medicine.drug
Zdroj: Nature Communications
Nature Communications, Nature Publishing Group, 2014, 5, pp.4187. ⟨10.1038/ncomms5187⟩
Nature Communications, 2014, 5, pp.4187. ⟨10.1038/ncomms5187⟩
ISSN: 2041-1723
DOI: 10.1038/ncomms5187⟩
Popis: International audience; Small ubiquitin-related modifier (SUMO) protein conjugation onto target proteins regulates multiple cellular functions, including defence against pathogens, stemness and senescence. SUMO1 peptides are limiting in quantity and are thus mainly conjugated to high-affinity targets. Conjugation of SUMO2/3 paralogues is primarily stress inducible and may initiate target degradation. Here we demonstrate that the expression of SUMO1/2/3 is dramatically enhanced by interferons through an miRNA-based mechanism involving the Lin28/let-7 axis, a master regulator of stemness. Normal haematopoietic progenitors indeed display much higher SUMO contents than their differentiated progeny. Critically, SUMOs contribute to the antiviral effects of interferons against HSV1 or HIV. Promyelocytic leukemia (PML) nuclear bodies are interferon-induced domains, which facilitate sumoylation of a subset of targets. Our findings thus identify an integrated interferon-responsive PML/SUMO pathway that impedes viral replication by enhancing SUMO conjugation and possibly also modifying the repertoire of targets. Interferon-enhanced post-translational modifications may be essential for senescence or stem cell self-renewal, and initiate SUMO-dependent proteolysis.
Databáze: OpenAIRE
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