Quantitative SUMO proteomics reveals the modulation of several PML nuclear body associated proteins and an anti-senescence function of UBC9

McManus, Francis P.; Bourdeau, Véronique; Acevedo, Mariana; Lopes-Paciência, Stéphane; Mignacca, Lian; Lamoliatte, Frederic; Pino, John W. Rojas; Ferbeyre, Gerardo; Thibault, Pierre

doi:10.1038/s41598-018-25150-z

Cited by 30 publications

(26 citation statements)

References 65 publications

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“…Therefore, non-SUMOylated PIAS1 can still localize, albeit less efficiently, to PML nuclear bodies via the SIM that is located on PIAS1 and the SUMOylated moieties on PML. A similar phenomenon was reported by our group for the SUMO E2 protein UBC9 34 . Taken together, these experiments confirmed that colocalization of PIAS1 at PML nuclear bodies is partly mediated by the SUMOylation of PIAS1 at Lys-137, Lys-238, and Lys-315 residues.…”

Section: Pias1 Overexpression Caused a Global Increase In Proteinsupporting

confidence: 88%

Quantitative SUMO proteomics identifies PIAS1 substrates involved in cell migration and motility

McManus

Plutoni

et al. 2020

Nat Commun

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The protein inhibitor of activated STAT1 (PIAS1) is an E3 SUMO ligase that plays important roles in various cellular pathways. Increasing evidence shows that PIAS1 is overexpressed in various human malignancies, including prostate and lung cancers. Here we used quantitative SUMO proteomics to identify potential substrates of PIAS1 in a system-wide manner. We identified 983 SUMO sites on 544 proteins, of which 62 proteins were assigned as putative PIAS1 substrates. In particular, vimentin (VIM), a type III intermediate filament protein involved in cytoskeleton organization and cell motility, was SUMOylated by PIAS1 at Lys-439 and Lys-445 residues. VIM SUMOylation was necessary for its dynamic disassembly and cells expressing a non-SUMOylatable VIM mutant showed a reduced level of migration. Our approach not only enables the identification of E3 SUMO ligase substrates but also yields valuable biological insights into the unsuspected role of PIAS1 and VIM SUMOylation on cell motility.

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Section: Pias1 Overexpression Caused a Global Increase In Proteinsupporting

confidence: 88%

Quantitative SUMO proteomics identifies PIAS1 substrates involved in cell migration and motility

McManus

Plutoni

et al. 2020

Nat Commun

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“…SUMOylation of p53 causes cellular senescence 82 , while deSUMOylation of Bmi1, a polycomb repressive complex member, is likewise, required for senescence 83 . Moreover, the SUMO E2 enzyme, Ubc9, regulates senescence by relocation of SUMOylated proteins to PML nuclear bodies 84 . Thus balanced protein SUMOylation is critical for stress resistance and survival.…”

Section: Discussionmentioning

confidence: 99%

SUMO promotes longevity and maintains mitochondrial homeostasis during ageing in Caenorhabditis elegans

Princz

Pelisch

Tavernarakis

2020

Sci Rep

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The insulin/IGF signalling pathway impacts lifespan across distant taxa, by controlling the activity of nodal transcription factors. In the nematode Caenorhabditis elegans, the transcription regulators DAF-16/FOXO and SKN-1/Nrf function to promote longevity under conditions of low insulin/IGF signalling and stress. The activity and subcellular localization of both DAF-16 and SKN-1 is further modulated by specific posttranslational modifications, such as phosphorylation and ubiquitination. Here, we show that ageing elicits a marked increase of SUMO levels in C. elegans. In turn, SUMO fine-tunes DAF-16 and SKN-1 activity in specific C. elegans somatic tissues, to enhance stress resistance. SUMOylation of DAF-16 modulates mitochondrial homeostasis by interfering with mitochondrial dynamics and mitophagy. Our findings reveal that SUMO is an important determinant of lifespan, and provide novel insight, relevant to the complexity of the signalling mechanisms that influence gene expression to govern organismal survival in metazoans.

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“…Proteins constitutively residing in PML bodies include the six nuclear PML isoforms, the speckled 100 kDa (Sp100) nuclear antigens, the death domain-associated protein (Daxx) and the small ubiquitin-like modifier (SUMO) family members SUMO1, SUMO2, SUMO3 and SUMO5 [13,14]. PML bodies are considered to be SUMOylation hubs, and most proteins associated with these organelles are post-translationally modified by one or more SUMO paralogs [12,15]. While SUMO1 attaches only as a monomer, SUMO2, SUMO3 and SUMO5 can form polymeric chains on target proteins including PML [14,16].…”

Section: Introductionmentioning

confidence: 99%

Revisiting promyelocytic leukemia protein targeting by human cytomegalovirus immediate-early protein 1

et al. 2020

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Promyelocytic leukemia (PML) bodies are nuclear organelles implicated in intrinsic and innate antiviral defense. The eponymous PML proteins, central to the self-organization of PML bodies, and other restriction factors found in these organelles are common targets of viral antagonism. The 72-kDa immediate-early protein 1 (IE1) is the principal antagonist of PML bodies encoded by the human cytomegalovirus (hCMV). IE1 is believed to disrupt PML bodies by inhibiting PML SUMOylation, while PML was proposed to act as an E3 ligase for IE1 SUMOylation. PML targeting by IE1 is considered to be crucial for hCMV replication at low multiplicities of infection, in part via counteracting antiviral gene induction linked to the cellular interferon (IFN) response. However, current concepts of IE1-PML interaction are largely derived from mutant IE1 proteins known or predicted to be metabolically unstable and globally misfolded. We performed systematic clustered charge-to-alanine scanning mutagenesis and identified a stable IE1 mutant protein (IE1cc172-176) with wild-type characteristics except for neither interacting with PML proteins nor inhibiting PML SUMOylation. Consequently, IE1cc172-176 does not associate with PML bodies and is selectively impaired for disrupting these organelles. Surprisingly, functional analysis of IE1cc172-176 revealed that the protein is hypermodified by mixed SUMO chains and that IE1 SUMOylation depends on nucleosome rather than PML binding. Furthermore, a mutant hCMV expressing IE1cc172-176 was only slightly attenuated compared to an IE1-null virus even at low multiplicities of infection. Finally, hCMV-induced expression of cytokine and IFN-stimulated genes turned out to be reduced rather than increased in the presence of IE1cc172-176 relative to wild-type IE1. Our findings challenge present views on the relationship of IE1 with PML and the role of PML in hCMV replication. This study also provides initial evidence for

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Quantitative SUMO proteomics reveals the modulation of several PML nuclear body associated proteins and an anti-senescence function of UBC9

Cited by 30 publications

References 65 publications

Quantitative SUMO proteomics identifies PIAS1 substrates involved in cell migration and motility

Quantitative SUMO proteomics identifies PIAS1 substrates involved in cell migration and motility

SUMO promotes longevity and maintains mitochondrial homeostasis during ageing in Caenorhabditis elegans

Revisiting promyelocytic leukemia protein targeting by human cytomegalovirus immediate-early protein 1

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