The &lt;b&gt;&lt;i&gt;Drosophila&lt;/i&gt;&lt;/b&gt; Deubiquitinating Enzyme dUSP36 Acts in the Hemocytes for Tolerance to &lt;b&gt;&lt;i&gt;Listeria monocytogenes&lt;/i&gt;&lt;/b&gt; Infections

Taillebourg, Emmanuel; Fauvarque, Marie-Odile

doi:10.1159/000360293

Cited by 5 publications

(4 citation statements)

References 35 publications

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“…The concept of tolerance (also termed resilience) provides an exciting, novel perspective on pathogen-host interactions in metazoans. A few examples of tolerance to bacterial or viral infections have been described in flies [ 42 – 48 ], but the mechanisms of tolerance remain largely unknown. In this study, we elucidate a novel epigenetics-based mechanism for tolerance.…”

Section: Discussionmentioning

confidence: 99%

The Epigenetic Regulator G9a Mediates Tolerance to RNA Virus Infection in Drosophila

et al. 2015

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Little is known about the tolerance mechanisms that reduce the negative effects of microbial infection on host fitness. Here, we demonstrate that the histone H3 lysine 9 methyltransferase G9a regulates tolerance to virus infection by shaping the response of the evolutionary conserved Jak-Stat pathway in Drosophila. G9a-deficient mutants are more sensitive to RNA virus infection and succumb faster to infection than wild-type controls, which was associated with strongly increased Jak-Stat dependent responses, but not with major differences in viral load. Genetic experiments indicate that hyperactivated Jak-Stat responses are associated with early lethality in virus-infected flies. Our results identify an essential epigenetic mechanism underlying tolerance to virus infection.

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Section: Discussionmentioning

confidence: 99%

The Epigenetic Regulator G9a Mediates Tolerance to RNA Virus Infection in Drosophila

et al. 2015

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“…Pathways that maintain cell homeostasis in response to internal and external stressors promote tolerance in response to infectious challenges in a variety of model organisms (Bessede et al, 2014; Ferreira et al, 2011; Richardson et al, 2010; Taillebourg et al, 2014). Thus, autophagy could contribute to tolerance as a major homeostatic pathway.…”

Section: Discussionmentioning

confidence: 99%

Autophagy Mediates Tolerance to Staphylococcus aureus Alpha-Toxin

Maurer

Reyes‐Robles

Alonzo

et al. 2015

Cell Host & Microbe

128

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SUMMARY Resistance and tolerance are two defense strategies employed by the host against microbial threats. Autophagy-mediated degradation of bacteria has been extensively described as a major resistance mechanism. Here we find that the dominant function of autophagy proteins during infections with the epidemic community-associated methicillin-resistant Staphylococcus aureus USA 300 is to mediate tolerance rather than resistance. Atg16L1 hypomorphic mice (Atg16L1HM), which have reduced autophagy, were highly susceptible to lethality in both sepsis and pneumonia models of USA300 infection. Autophagy confers protection by limiting the damage caused by α-toxin, particularly to endothelial cells. Remarkably, Atg16L1HM mice display enhanced survival rather than susceptibility upon infection with α-toxin deficient S. aureus. These results identify an essential role for autophagy in tolerance to Staphylococcal disease and highlight how a single virulence factor encoded by a pathogen can determine whether a given host factor promotes tolerance or resistance.

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“…While no obvious homolog of human USP28 is present in the Drosophila genome, USP36 has a clear Drosophila ortholog encoded by the dUsp36 gene (Thevenon et al, 2009), also known as scrawny (scny) (Buszczak et al, 2009) or emperor's thumb (et) (Ribaya et al, 2009). Its known functions include immunity (Thevenon et al, 2009;Taillebourg et al, 2014), stem cell maintenance (Buszczak et al, 2009), apoptosis (Ribaya et al, 2009), autophagy and cell growth (Taillebourg et al, 2012). dUSP36 has been shown to deubiquitinate histone H2B, which accounts for its role in stem cell maintenance (Buszczak et al, 2009), and the NF-kB pathway signaling protein IMD, which accounts for its role in immune signaling (Thevenon et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

A Nucleolar Isoform of the Drosophila Ubiquitin Specific Protease dUSP36 Regulates MYC-Dependent Cell Growth

Thevenon

Seffouh

Pillet

et al. 2020

Front. Cell Dev. Biol.

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The c-Myc oncogene is a transcription factor that regulates the expression of a very large set of genes mainly involved in cell growth and proliferation. It is overexpressed in more than 70% of human cancers, illustrating the importance of keeping its levels and activity under control. The ubiquitin proteasome system is a major regulator of MYC levels in humans as well as in model organisms such as Drosophila melanogaster.Although the E3 ligases that promote MYC ubiquitination have been largely investigated, the identity and the role of the deubiquitinating enzymes, which counteract their action is only beginning to be unraveled. Using isoform-specific CRISPR-Cas9 mutagenesis, we show that the Drosophila homolog of the Ubiquitin Specific Protease USP36 has different isoforms with specific sub-cellular localizations and that the nucleolar dUSP36-D isoform is specifically required for cell and organismal growth. We also demonstrate that this isoform interacts with dMYC and the E3 ligase AGO and regulates their stability and ubiquitination levels. Furthermore, we show that dUSP36 is ubiquitinated by AGO and is able to self-deubiquitinate. Finally, we provide in vivo evidence supporting the functional relevance of these regulatory relationships. Together these results reveal that dMYC, AGO and dUSP36 form a tripartite, evolutionary conserved complex that acts as a regulatory node to control dMYC protein levels.

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The <b><i>Drosophila</i></b> Deubiquitinating Enzyme dUSP36 Acts in the Hemocytes for Tolerance to <b><i>Listeria monocytogenes</i></b> Infections

Cited by 5 publications

References 35 publications

The Epigenetic Regulator G9a Mediates Tolerance to RNA Virus Infection in Drosophila

The Epigenetic Regulator G9a Mediates Tolerance to RNA Virus Infection in Drosophila

Autophagy Mediates Tolerance to Staphylococcus aureus Alpha-Toxin

A Nucleolar Isoform of the Drosophila Ubiquitin Specific Protease dUSP36 Regulates MYC-Dependent Cell Growth

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