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

Şahin, Umut; Ferhi, Omar; Jeanne, Marion; Benhenda, Shirine; Berthier, Christine; Jollivet, Florence; Niwa‐Kawakita, Michiko; Faklaris, Orestis; Setterblad, Niclas; Thé, Hugues de; Lallemand-Breitenbach, Valérie

doi:10.1083/jcb.201305148

Cited by 194 publications

(332 citation statements)

References 74 publications

Supporting

Mentioning

296

Contrasting

Unclassified

Order By: Relevance

“…Thus, our observations predict a profound change in the repertoire of SUMO1-conjugated proteins on IFN exposure. PML, another IFN-induced protein 39 , promotes sumoylation by favouring interactions between UBC9, the universal SUMO E2 ligase and specific partners within PML NBs 12 . Several of these partners are themselves transcriptionally controlled by IFN, notably SP100 (ref.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, in the absence of PML, RanGAP1 sumoylation was considerably more enhanced by IFN ( Supplementary Fig. 4c), while efficient IFNinduced SP100 sumoylation is known to require PML 12 . IFN antiviral effect against HSV1 was impeded by PML silencing (11-fold reduction, Fig.…”

Section: Ifn-induced Sumos Are Required For Ifn Antiviral Effectsmentioning

confidence: 99%

“…Thus, SUMOs are critical downstream mediators of IFN antiviral effect. IFN-inducible PML protein has intrinsic antiviral activity 32,33 and promotes sumoylation of specific substrates recruited on PML NBs 12 . This suggested that PML might redirect IFN-induced SUMOs towards PML NB partners, such as SP100, rather than non-NB-partner proteins such as RanGAP1.…”

Section: Ifn-induced Sumos Are Required For Ifn Antiviral Effectsmentioning

confidence: 99%

“…Sumoylation is essential for life 9 and regulates many biological processes, particularly stress responses 10,11 . We recently demonstrated a role for PML nuclear bodies (NBs), spherical structures organized by PML protein, in oxidative stress-responsive sumoylation 12 . There is significant evidence that SUMO conjugation opposes viral or bacterial replication and pathogens inactivate SUMO conjugation through multiple mechanisms [13][14][15] .…”

mentioning

confidence: 99%

See 3 more Smart Citations

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

Şahin¹,

Ferhi²,

Carnec³

et al. 2014

Nat Commun

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Ifn-induced Sumos Are Required For Ifn Antiviral Effectsmentioning

confidence: 99%

Section: Ifn-induced Sumos Are Required For Ifn Antiviral Effectsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

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

Şahin¹,

Ferhi²,

Carnec³

et al. 2014

Nat Commun

Self Cite

View full text Add to dashboard Cite

show abstract

“…As observed by electron or super resolution microscopy, NBs are spherical structures of 0.1-1 mm in diameter. 7,[25][26][27] Immunoelectron or high resolution confocal analyses indicate that the PML protein forms the outer shell, whereas partner proteins are concentrated in the inner core. 26,[28][29][30] The outer PML shell is associated with the nuclear matrix, a loosely defined, insoluble nuclear scaffold that is resistant to nuclease and high salt extraction and thought to support nuclear organization and compartmentalization.…”

Section: A Brief Historymentioning

confidence: 99%

PML nuclear bodies: Assembly and oxidative stress-sensitive sumoylation

Şahin¹,

Lallemand-Breitenbach²

2014

Nucleus

Self Cite

View full text Add to dashboard Cite

ATO (Arsenic Trioxide) Effects on Promyelocytic Leukemia Nuclear Bodies Reveals Antiviral Intervention Capacity

et al. 2020

View full text Add to dashboard Cite

Human adenoviruses (HAdV) are associated with clinical symptoms such as gastroenteritis, keratoconjunctivitis, pneumonia, hepatitis, and encephalitis. In the absence of protective immunity, as in allogeneic bone marrow transplant patients, HAdV infections can become lethal. Alarmingly, various outbreaks of highly pathogenic, pneumotropic HAdV types have been recently reported, causing severe and lethal respiratory diseases. Effective drugs for treatment of HAdV infections are still lacking. The repurposing of drugs approved for other indications is a valuable alternative for the development of new antiviral therapies and is less risky and costly than de novo development. Arsenic trioxide (ATO) is approved for treatment of acute promyelocytic leukemia. Here, it is shown that ATO is a potent inhibitor of HAdV. ATO treatment blocks virus expression and replication by reducing the number and integrity of promyelocytic leukemia (PML) nuclear bodies, important subnuclear structures for HAdV replication. Modification of HAdV proteins with small ubiquitin‐like modifiers (SUMO) is also key to HAdV replication. ATO reduces levels of viral SUMO‐E2A protein, while increasing SUMO‐PML, suggesting that ATO interferes with SUMOylation of proteins crucial for HAdV replication. It is concluded that ATO targets cellular processes key to HAdV replication and is relevant for the development of antiviral intervention strategies.

show abstract

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

Abstract: PML multimerization into nuclear bodies following its oxidation promotes sumoylation and sequestration of partner proteins in these structures.

Cited by 194 publications

References 74 publications

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

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

PML nuclear bodies: Assembly and oxidative stress-sensitive sumoylation

ATO (Arsenic Trioxide) Effects on Promyelocytic Leukemia Nuclear Bodies Reveals Antiviral Intervention Capacity

Contact Info

Product

Resources

About