Conserved Nutrient Sensor O-GlcNAc Transferase Is Integral to C. elegans Pathogen-Specific Immunity

Bond, Michelle; Ghosh, Salil; Wang, Peng; Hanover, John A.

doi:10.1371/journal.pone.0113231

Cited by 31 publications

(45 citation statements)

References 59 publications

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“…These phenotypes can all be linked to changes in insulin signaling in mutant nematodes (110,116), which suggest that regulating insulin signaling is a conserved role for OGT from C. elegans to mammals (15). OGT-1 removal also appeared to affect genes involved in innate immunity (116,119) and stress response (116).…”

Section: Caenorhabditis Elegans Do Not Require Ogt-1 For Viabilitymentioning

confidence: 99%

The Biochemistry of O-GlcNAc Transferase: Which Functions Make It Essential in Mammalian Cells?

Levine

Walker

2016

Annu. Rev. Biochem.

159

165

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O-linked N-acetylglucosamine transferase (OGT) is found in all metazoans and plays an important role in development but at the single-cell level is only essential in dividing mammalian cells. Postmitotic mammalian cells and cells of invertebrates such as Caenorhabditis elegans and Drosophila can survive without copies of OGT. Why OGT is required in dividing mammalian cells but not in other cells remains unknown. OGT has multiple biochemical activities. Beyond its well-known role in adding β-O-GlcNAc to serine and threonine residues of nuclear and cytoplasmic proteins, OGT also acts as a protease in the maturation of the cell cycle regulator host cell factor 1 (HCF-1) and serves as an integral member of several protein complexes, many of them linked to gene expression. In this review, we summarize current understanding of the mechanisms underlying OGT's biochemical activities and address whether known functions of OGT could be related to its essential role in dividing mammalian cells.

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Section: Caenorhabditis Elegans Do Not Require Ogt-1 For Viabilitymentioning

confidence: 99%

The Biochemistry of O-GlcNAc Transferase: Which Functions Make It Essential in Mammalian Cells?

Levine

Walker

2016

Annu. Rev. Biochem.

159

165

View full text Add to dashboard Cite

show abstract

“…To further test the above hypotheses, we assessed the presence of the GATA motif in the promoter regions of the transcriptional targets of immunity regulators, including additional transcription factors such as xbp-1 (Henis-Korenblit et al, 2010), elt-2 Shapira et al, 2006), and hif-1 (Bishop et al, 2004), or immune signalling pathway components such as pmk-1 (Bond et al, 2014), dbl-1 (Roberts et al, 2010), and dkf-2 (Ren et al, 2009), or other types of regulators such as npr-1 (Andersen et al, 2014). The targets were inferred from transcriptome data for these genes, as available from WormExp.…”

Section: Gata Motifs Are Enriched In the Targets Of Other Immune-relamentioning

confidence: 99%

“…Moreover, several expression analyses explored the downstream targets of immunity pathways, allowing us to assess the presence of shared or divergent signatures in the differentially expressed gene sets. Such expression analyses have been performed with mutants of the p38 MAPK, JNK MAPK, TGF-␤ and the ILR cascades (for example pmk-1(km25) for p38 MAPK (Bond et al, 2014), jun-1(gk557) for JNK (Uno et al, 2013), dbl-1(ctIs40) overexpression for TGF-␤ (Roberts et al, 2010) and daf-16(mu86) for ILR (Murphy et al, 2003)). Similar expression analysis was performed for mutants of GATA transcription factors, including a mutant for the GATA transcription factor gene elt-2, which is known to contribute to immunity against some gut-infecting pathogens such as Pseudomonas aeruginosa, Salmonella typhimurium, Enterococcus faecalis, Cryptococcus neoformans or Burkholderia pseudomallei (Kerry et al, 2006;Shapira et al, 2006;Lee et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

GATA transcription factor as a likely key regulator of the Caenorhabditis elegans innate immune response against gut pathogens

Yang

Dierking

Rosenstiel

et al. 2016

Zoology

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Invertebrate defence against pathogens exclusively relies on components of the innate immune system. Comprehensive information has been collected over the last years on the molecular components of invertebrate immunity and the involved signalling processes, especially for the main invertebrate model species, the fruitfly Drosophila melanogaster and the nematode Caenorhabditis elegans. Yet, the exact regulation of general and specific defences is still not well understood. In the current study, we take advantage of a recently established database, WormExp, which combines all available gene expression studies for C. elegans, in order to explore commonalities and differences in the regulation of nematode immune defence against a large variety of pathogens versus food microbes. We identified significant overlaps in the transcriptional response towards microbes, especially pathogenic bacteria. We also found that the GATA motif is overrepresented in many microbe-induced gene sets and in targets of other previously identified regulators of worm immunity. Moreover, the activated targets of one of the known C. elegans GATA transcription factors, ELT-2, are significantly enriched in the gene sets, which are differentially regulated by gut-infecting pathogens. These findings strongly suggest that GATA transcription factors and particularly ELT-2 play a central role in regulating the C. elegans immune response against gut pathogens. More specific responses to distinct pathogens may be mediated by additional transcription factors, either acting alone or jointly with GATA transcription factors. Taken together, our analysis of the worm's transcriptional response to microbes provides a new perspective on the C. elegans immune system, which we propose to be coordinated by GATA transcription factor ELT-2 in the gut.

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“…The process of glycosylation is controlled by secondary structural motifs (Julenius et al, 2005), the cellular repertoire of glycosyltransferases and their localization within the Golgi apparatus resulting in distinct cellular profiles (Hanisch, 2001). O-linked glycosylation has been shown to be integral in immune protection across the animal phyla (Tsuboi and Fukuda, 2001;Bond et al, 2014). Following posttranslational modification, mucins are either tethered to the epithelial cell surface or secreted into the surrounding environment forming the SML.…”

Section: Introductionmentioning

confidence: 99%

Viruses and the origin of microbiome selection and immunity

et al. 2016

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The last common metazoan ancestor (LCMA) emerged over half a billion years ago. These complex metazoans provided newly available niche space for viruses and microbes. Modern day contemporaries, such as cnidarians, suggest that the LCMA consisted of two cell layers: a basal endoderm and a mucus-secreting ectoderm, which formed a surface mucus layer (SML). Here we propose a model for the origin of metazoan immunity based on external and internal microbial selection mechanisms. In this model, the SML concentrated bacteria and their associated viruses (phage) through physical dynamics (that is, the slower flow fields near a diffusive boundary layer), which selected for mucin-binding capabilities. The concentration of phage within the SML provided the LCMA with an external microbial selective described by the bacteriophage adherence to mucus (BAM) model. In the BAM model, phage adhere to mucus protecting the metazoan host against invading, potentially pathogenic bacteria. The same fluid dynamics that concentrated phage and bacteria in the SML also concentrated eukaryotic viruses. As eukaryotic viruses competed for host intracellular niche space, those viruses that provided the LCMA with immune protection were maintained. If a resident virus became pathogenic or if a non-beneficial infection occurred, we propose that tumor necrosis factor (TNF)-mediated programmed cell death, as well as other apoptosis mechanisms, were utilized to remove virally infected cells. The ubiquity of the mucosal environment across metazoan phyla suggest that both BAM and TNF-induced apoptosis emerged during the Precambrian era and continue to drive the evolution of metazoan immunity.

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Conserved Nutrient Sensor O-GlcNAc Transferase Is Integral to C. elegans Pathogen-Specific Immunity

Cited by 31 publications

References 59 publications

The Biochemistry of O-GlcNAc Transferase: Which Functions Make It Essential in Mammalian Cells?

The Biochemistry of O-GlcNAc Transferase: Which Functions Make It Essential in Mammalian Cells?

GATA transcription factor as a likely key regulator of the Caenorhabditis elegans innate immune response against gut pathogens

Viruses and the origin of microbiome selection and immunity

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