Large-scale analysis of lysine SUMOylation by SUMO remnant immunoaffinity profiling

Lamoliatte, Frederic; Caron, Danielle; Durette, Chantal; Mahrouche, Louiza; Maroui, Mohamed Ali; Caron-Lizotte, Olivier; Bonneil, Éric; Chelbi-Alix, Mounira K.; Thibault, Pierre

doi:10.1038/ncomms6409

Cited by 119 publications

(126 citation statements)

References 43 publications

(58 reference statements)

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“…In accordance with the His 6 precipitation data presented here, previous reports suggest that only SUMO1 is conjugated to EXOSC10; multiple mass spectrometry analyzes of affinity tagged SUMO1 conjugates, but not SUMO2 or SUMO3, identified EXOSC10 as a SUMO target (Zhao et al 2004;Matic et al 2010;Westman et al 2010;Impens et al 2014;Lamoliatte et al 2014). In accordance with this, a screen of the endogenous SUMOylated proteome identified EXOSC10 conjugation to SUMO1 but not SUMO2 (Becker et al 2013).…”

Section: Implications Of Exosc10 Sumoylationsupporting

confidence: 92%

“…Indeed, other exosome subunits appear in screens for SUMOylated proteins, such as EXOSC5 (Becker et al 2013;Hendriks et al 2015) and EXOSC9 (Golebiowski et al 2009;Impens et al 2014;Lamoliatte et al 2014;Hendriks et al 2015). Furthermore, SUMO site prediction tools identify putative sites in EXOSC2, EXOSC3, EXOSC7, EXOSC8, and EXOSC9 (Zhao et al 2014) and SUMOplot.…”

Section: Implications Of Exosc10 Sumoylationmentioning

confidence: 99%

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Cooling-induced SUMOylation of EXOSC10 down-regulates ribosome biogenesis

Knight

Bastide

Peretti

et al. 2016

RNA

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The RNA exosome is essential for 3 ′ processing of functional RNA species and degradation of aberrant RNAs in eukaryotic cells. Recent reports have defined the substrates of the exosome catalytic domains and solved the multimeric structure of the exosome complex. However, regulation of exosome activity remains poorly characterized, especially in response to physiological stress. Following the observation that cooling of mammalian cells results in a reduction in 40S:60S ribosomal subunit ratio, we uncover regulation of the nuclear exosome as a result of reduced temperature. Using human cells and an in vivo model system allowing whole-body cooling, we observe reduced EXOSC10 (hRrp6, Pm/Scl-100) expression in the cold. In parallel, both models of cooling increase global SUMOylation, leading to the identification of specific conjugation of SUMO1 to EXOSC10, a process that is increased by cooling. Furthermore, we define the major SUMOylation sites in EXOSC10 by mutagenesis and show that overexpression of SUMO1 alone is sufficient to suppress EXOSC10 abundance. Reducing EXOSC10 expression by RNAi in human cells correlates with the 3 ′ preribosomal RNA processing defects seen in the cold as well as reducing the 40S:60S ratio, a previously uncharacterized consequence of EXOSC10 suppression. Together, this work illustrates that EXOSC10 can be modified by SUMOylation and identifies a physiological stress where this regulation is prevalent both in vitro and in vivo.

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Section: Implications Of Exosc10 Sumoylationsupporting

confidence: 92%

Section: Implications Of Exosc10 Sumoylationmentioning

confidence: 99%

Cooling-induced SUMOylation of EXOSC10 down-regulates ribosome biogenesis

Knight

Bastide

Peretti

et al. 2016

RNA

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“…The covalent attachment of the small SUMO moiety to substrate proteins has recently emerged as a main regulatory system, leading to dramatic changes in the SUMO proteome (31)(32)(33)(34) with consequences on IFN responses and antiviral defense mechanisms (9,10,27).…”

Section: Discussionmentioning

confidence: 99%

MxA Mediates SUMO-Induced Resistance to Vesicular Stomatitis Virus

Maarifi

Hannoun

Geoffroy

et al. 2016

J Virol

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Multiple cellular pathways are regulated by small ubiquitin-like modifier (SUMO) modification, including ubiquitin-mediated proteolysis, signal transduction, innate immunity, and antiviral defense. In the study described in this report, we investigated the effects of SUMO on the replication of two members of the Rhabdoviridae family, vesicular stomatitis virus (VSV) and rabies virus (RABV). We show that stable expression of SUMO in human cells confers resistance to VSV infection in an interferon-independent manner. We demonstrate that SUMO expression did not alter VSV entry but blocked primary mRNA synthesis, leading to a reduction of viral protein synthesis and viral production, thus protecting cells from VSV-induced cell lysis. MxA is known to inhibit VSV primary transcription. Interestingly, we found that the MxA protein was highly stabilized in SUMO-expressing cells. Furthermore, extracts from cells stably expressing SUMO exhibited an increase in MxA oligomers, suggesting that SUMO plays a role in protecting MxA from degradation, thus providing a stable intracellular pool of MxA available to combat invading viruses. Importantly, MxA depletion in SUMO-expressing cells abrogated the anti-VSV effect of SUMO. Furthermore, SUMO expression resulted in interferon-regulatory factor 3 (IRF3) SUMOylation, subsequently decreasing RABV-induced IRF3 phosphorylation and interferon synthesis. As expected, this rendered SUMO-expressing cells more sensitive to RABV infection, even though MxA was stabilized in SUMO-expressing cells, since its expression did not confer resistance to RABV. Our findings demonstrate opposing effects of SUMO expression on two viruses of the same family, intrinsically inhibiting VSV infection through MxA stabilization while enhancing RABV infection by decreasing IFN induction. IMPORTANCEWe report that SUMO expression reduces interferon synthesis upon RABV or VSV infection. Therefore, SUMO renders cells more sensitive to RABV but unexpectedly renders cells resistant to VSV by blocking primary mRNA synthesis. Unlike the interferon-mediated innate immune response, intrinsic antiviral resistance is mediated by constitutively expressed restriction factors. Among the various anti-VSV restriction factors, only MxA is known to inhibit VSV primary transcription, and we show here that its expression does not alter RABV infection. Interestingly, MxA depletion abolished the inhibition of VSV by SUMO, demonstrating that MxA mediates SUMO-induced intrinsic VSV resistance. Furthermore, MxA oligomerization is known to be critical for its protein stability, and we show that higher levels of oligomers were formed in cells expressing SUMO than in wildtype cells, suggesting that SUMO may play a role in protecting MxA from degradation, providing a stable intracellular pool of MxA able to protect cells from viral infection. In addition to ubiquitin, several ubiquitin-like (UBL) proteins have been reported to function as protein modifiers that regulate various cellular functions (1). The best-characterized member...

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“…In recent years, several efforts have been made to study sumoylation on a global and site-specific manner by high resolution mass spectrometry (14,15,(51)(52)(53)(54). Reanalyzing all these available data sets (13) revealed that at physiological conditions, at least half of the SUMO substrates are modified at the minimal KxE motif, although upon stress, more lysines at non-SCM sites are modified.…”

Section: The Sumo Consensus Motifmentioning

confidence: 99%

SUMO conjugation – a mechanistic view

Pichler

Fatouros

Lee

et al. 2017

Biomolecular Concepts

212

223

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Abstract:The regulation of protein fate by modification with the small ubiquitin-related modifier (SUMO) plays an essential and crucial role in most cellular pathways. Sumoylation is highly dynamic due to the opposing activities of SUMO conjugation and SUMO deconjugation. SUMO conjugation is performed by the hierarchical action of E1, E2 and E3 enzymes, while its deconjugation involves SUMO-specific proteases. In this review, we summarize and compare the mechanistic principles of how SUMO gets conjugated to its substrate. We focus on the interplay of the E1, E2 and E3 enzymes and discuss how specificity could be achieved given the limited number of conjugating enzymes and the thousands of substrates.

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Large-scale analysis of lysine SUMOylation by SUMO remnant immunoaffinity profiling

Cited by 119 publications

References 43 publications

Cooling-induced SUMOylation of EXOSC10 down-regulates ribosome biogenesis

Cooling-induced SUMOylation of EXOSC10 down-regulates ribosome biogenesis

MxA Mediates SUMO-Induced Resistance to Vesicular Stomatitis Virus

SUMO conjugation – a mechanistic view

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