The macroPARP genes <i>parp‐9</i> and <i>parp‐14</i> are developmentally and differentially regulated in mouse tissues

Hakmé, Antoinette; Huber, Aline; Dollé, Pascal; Schreiber, Valérie

doi:10.1002/dvdy.21399

Cited by 28 publications

(32 citation statements)

References 19 publications

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“…Several poly [ADP-ribose] polymerases (Parp9, Parp12 and Parp14) and Dtx3l, an E3 ubiquitin ligase co-regulated with Parp9 through a shared promoter, were also up-regulated in every tissue tested and functionally annotate to DNA repair [57], [58]. Together the expression of Zbp1, a DNA sensor, and multiple DNA damage/repair genes suggests that the host-wide IFN-signature reported here might be driven by multi-organ cellular injury.…”

Section: Discussionmentioning

confidence: 63%

Late Multiple Organ Surge in Interferon-Regulated Target Genes Characterizes Staphylococcal Enterotoxin B Lethality

et al. 2014

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BackgroundBacterial superantigens are virulence factors that cause toxic shock syndrome. Here, the genome-wide, temporal response of mice to lethal intranasal staphylococcal enterotoxin B (SEB) challenge was investigated in six tissues.ResultsThe earliest responses and largest number of affected genes occurred in peripheral blood mononuclear cells (PBMC), spleen, and lung tissues with the highest content of both T-cells and monocyte/macrophages, the direct cellular targets of SEB. In contrast, the response of liver, kidney, and heart was delayed and involved fewer genes, but revealed a dominant genetic program that was seen in all 6 tissues. Many of the 85 uniquely annotated transcripts participating in this shared genomic response have not been previously linked to SEB. Nine of the 85 genes were subsequently confirmed by RT-PCR in every tissue/organ at 24 h. These 85 transcripts, up-regulated in all tissues, annotated to the interferon (IFN)/antiviral-response and included genes belonging to the DNA/RNA sensing system, DNA damage repair, the immunoproteasome, and the ER/metabolic stress-response and apoptosis pathways. Overall, this shared program was identified as a type I and II interferon (IFN)-response and the promoters of these genes were highly enriched for IFN regulatory matrices. Several genes whose secreted products induce the IFN pathway were up-regulated at early time points in PBMCs, spleen, and/or lung. Furthermore, IFN regulatory factors including Irf1, Irf7 and Irf8, and Zbp1, a DNA sensor/transcription factor that can directly elicit an IFN innate immune response, participated in this host-wide SEB signature.ConclusionGlobal gene-expression changes across multiple organs implicated a host-wide IFN-response in SEB-induced death. Therapies aimed at IFN-associated innate immunity may improve outcome in toxic shock syndromes.

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Section: Discussionmentioning

confidence: 63%

Late Multiple Organ Surge in Interferon-Regulated Target Genes Characterizes Staphylococcal Enterotoxin B Lethality

et al. 2014

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“…As PARP3, PARP9 and PARP14 have been reported to be prominently expressed in thymus 37, 38 they are candidates for further exploration of TCDD effects in the thymus.…”

Section: Discussionmentioning

confidence: 99%

NAD+ loss, a new player in AhR biology: prevention of thymus atrophy and hepatosteatosis by NAD+ repletion

Diani-Moore¹,

Shoots²,

Singh³

et al. 2017

Sci Rep

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Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) is a carcinogenic and highly toxic industrial byproduct that persists in the environment and produces a pleiotropic toxicity syndrome across vertebrate species that includes wasting, hepatosteatosis, and thymus atrophy. Dioxin toxicities require binding and activation of the aryl hydrocarbon receptor (AhR), a ligand activated transcription factor. However, after nearly 50 years of study, it remains unknown how AhR activation by dioxin produces toxic effects. Here, using the chick embryo close to hatching, a well-accepted model for dioxin toxicity, we identify NAD+ loss through PARP activation as a novel unifying mechanism for diverse effects of dioxin in vivo. We show that NAD+ loss is attributable to increased PARP activity in thymus and liver, as cotreatment with dioxin and the PARP inhibitor PJ34 increased NAD+ levels and prevented both thymus atrophy and hepatosteatosis. Our findings additionally support a role for decreased NAD+ dependent Sirt6 activity in mediating dioxin toxicity following PARP activation. Strikingly, treatment in vivo with the NAD+ repleting agent nicotinamide, a form of vitamin B3, prevented thymus atrophy and hepatosteatosis by dioxin and increased sirtuin activity, providing a therapeutic approach for preventing dioxin toxicities in vivo.

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“…in the so-called macroPARPs (PARP-9 and PARP-14) [49]. There are 18 human genes for members of the PARP family; the prototype enzyme, PARP-1, catalyzes the post-translational modification of many substrate proteins, including itself, in a multitude of cellular processes (DNA repair, transcriptional regulation, energy metabolism, and apoptosis) [50][51][52].…”

Section: Discussionmentioning

confidence: 99%

The SARS-Unique Domain (SUD) of SARS Coronavirus Contains Two Macrodomains That Bind G-Quadruplexes

Tan¹,

Hilgenfeld²

2009

SciVee

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Since the outbreak of severe acute respiratory syndrome (SARS) in 2003, the three-dimensional structures of several of the replicase/transcriptase components of SARS coronavirus (SARS-CoV), the non-structural proteins (Nsps), have been determined. However, within the large Nsp3 (1922 amino-acid residues), the structure and function of the so-called SARSunique domain (SUD) have remained elusive. SUD occurs only in SARS-CoV and the highly related viruses found in certain bats, but is absent from all other coronaviruses. Therefore, it has been speculated that it may be involved in the extreme pathogenicity of SARS-CoV, compared to other coronaviruses, most of which cause only mild infections in humans. In order to help elucidate the function of the SUD, we have determined crystal structures of fragment 389-652 (''SUD core '') of Nsp3, which comprises 264 of the 338 residues of the domain. Both the monoclinic and triclinic crystal forms (2.2 and 2.8 Å resolution, respectively) revealed that SUD core forms a homodimer. Each monomer consists of two subdomains, SUD-N and SUD-M, with a macrodomain fold similar to the SARS-CoV X-domain. However, in contrast to the latter, SUD fails to bind ADP-ribose, as determined by zone-interference gel electrophoresis. Instead, the entire SUD core as well as its individual subdomains interact with oligonucleotides known to form G-quadruplexes. This includes oligodeoxy-as well as oligoribonucleotides. Mutations of selected lysine residues on the surface of the SUD-N subdomain lead to reduction of Gquadruplex binding, whereas mutations in the SUD-M subdomain abolish it. As there is no evidence for Nsp3 entering the nucleus of the host cell, the SARS-CoV genomic RNA or host-cell mRNA containing long G-stretches may be targets of SUD. The SARS-CoV genome is devoid of G-stretches longer than 5-6 nucleotides, but more extended G-stretches are found in the 39-nontranslated regions of mRNAs coding for certain host-cell proteins involved in apoptosis or signal transduction, and have been shown to bind to SUD in vitro. Therefore, SUD may be involved in controlling the host cell's response to the viral infection. Possible interference with poly(ADP-ribose) polymerase-like domains is also discussed.

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The macroPARP genes parp‐9 and parp‐14 are developmentally and differentially regulated in mouse tissues

Cited by 28 publications

References 19 publications

Late Multiple Organ Surge in Interferon-Regulated Target Genes Characterizes Staphylococcal Enterotoxin B Lethality

Late Multiple Organ Surge in Interferon-Regulated Target Genes Characterizes Staphylococcal Enterotoxin B Lethality

NAD+ loss, a new player in AhR biology: prevention of thymus atrophy and hepatosteatosis by NAD+ repletion

The SARS-Unique Domain (SUD) of SARS Coronavirus Contains Two Macrodomains That Bind G-Quadruplexes

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