ADP-ribosylation: from molecular mechanisms to human disease

Hoch, Nicolas C.; Polo, Luis Mariano

doi:10.1590/1678-4685-gmb-2019-0075

Cited by 40 publications

(37 citation statements)

References 162 publications

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“…Cellular component analysis of this set of 52 proteins indicates a significant enrichment in nuclear, cytoskeleton and chromatin contained proteins (Fig. 4E, Supplementary Table S7), in line with the well described role of PAR in the nucleus, nuclear organization, chromatin organization, relaxation and transcriptional regulation (Hassa et al, 2006;Hoch and Polo, 2019;Leung, 2014; Thomas and Tulin, 2013). This finding may indicate a crosstalk between PARylation and phosphorylation with regards to nuclear structure and chromatin organization.…”

Section: Crosstalk Between Progestin Induced Phosphorylation and Parysupporting

confidence: 79%

Signalling Network of Breast Cancer Cells in Response to Progesterone

Wright

Vastolo

et al. 2020

Preprint

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Breast cancer cells enter into the cell cycle following progestin exposure by the activation of signalling cascades involving a plethora of enzymes, transcription factors and co-factors that transmit the external signal from the cell membrane to chromatin, ultimately leading to a change of the gene expression program. Although many of the events within the signalling network have been described in isolation, how they globally team up to generate the final cell response is unclear. In this study we use antibody microarrays and phosphoproteomics to provide a dynamic global signalling map that reveals new key regulated proteins and links between previously known and novel pathways. Detailed analysis of the data revealed intriguing changes in protein complexes involved in nuclear structure, EMT, cell adhesion, as well as transcription factors previously not associated with breast cancer proliferation. As different post-translational modifications can mediate complex crosstalk mechanisms and massive PARylation is also rapidly induced by progestins, we provide details of important chromatin regulatory complexes containing both phosphorylated and PARylated proteins. This study contributes an important resource for the scientific community, as it identifies novel players and connections meaningful for breast cancer cell biology and potentially relevant for cancer management.

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Section: Crosstalk Between Progestin Induced Phosphorylation and Parysupporting

confidence: 79%

Signalling Network of Breast Cancer Cells in Response to Progesterone

Wright

Vastolo

et al. 2020

Preprint

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“…ADP-ribosylation is a posttranslational modification where ADP-ribose molecules are covalently attached to target proteins at one of several different amino acids including glutamate, aspartate, cysteine, lysine, arginine, and serine [12,13]. Additionally, it has been shown that ADP-ribose molecules can be added to nucleic acids [14]. The ADP-ribose is transferred from nicotinamide adenine dinucleotide (NAD+) onto target proteins as a single molecule of ADP-ribose (mono-ADP-ribose (MAR)) [8] or as consecutive individual units to form polymers of ADP-ribose molecules (poly-ADP-ribose (PAR)) by ADP-ribosyl transferases (ARTs) including the poly-ADP-ribose polymerases (PARPs) [15].…”

Section: Adp-ribosylation and The Innate Immune Responsementioning

confidence: 99%

The Viral Macrodomain Counters Host Antiviral ADP-Ribosylation

Alhammad

Fehr

2020

Viruses

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Macrodomains, enzymes that remove ADP-ribose from proteins, are encoded by several families of RNA viruses and have recently been shown to counter innate immune responses to virus infection. ADP-ribose is covalently attached to target proteins by poly-ADP-ribose polymerases (PARPs), using nicotinamide adenine dinucleotide (NAD+) as a substrate. This modification can have a wide variety of effects on proteins including alteration of enzyme activity, protein–protein interactions, and protein stability. Several PARPs are induced by interferon (IFN) and are known to have antiviral properties, implicating ADP-ribosylation in the host defense response and suggesting that viral macrodomains may counter this response. Recent studies have demonstrated that viral macrodomains do counter the innate immune response by interfering with PARP-mediated antiviral defenses, stress granule formation, and pro-inflammatory cytokine production. Here, we will describe the known functions of the viral macrodomains and review recent literature demonstrating their roles in countering PARP-mediated antiviral responses.

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“…This can prevent cell death in the cellular stress settings, although its over-accumulation, in turn, leads to cell death. To address this, the ADPRHL2 (ADP-Ribosylhydrolase like 2; NM_017825.2; MIM: 610624) gene containing 6 coding exons encodes an ADP-ribosylhydrolase enzyme [ 8 ]. This enzyme eliminates the proteins’ post-translational addition of poly-ADP ribose (PAR) in cellular stress.…”

Section: Introductionmentioning

confidence: 99%

Novel imaging and clinical phenotypes of CONDSIAS disorder caused by a homozygous frameshift variant of ADPRHL2: a case report

et al. 2020

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Background: Stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS) is an autosomal recessive disorder caused by defects in the ADP-Ribosylhydrolase Like 2 (ADPRHL2; OMIM: 618170) gene. This gene encodes the ADP-ribosylhydrolase enzyme (ARH3) that eliminates the addition of poly-ADP ribose (PAR) in the cellular stress onto proteins in the ADP-ribosylation process in which adding one or more ADP-ribose moieties onto the target proteins in the post-translational modification have occurred. In this study, we report a new case of CONDSIAS in the Iranian population. A literature review of CONDSIAS is also included. Case presentation: A four-year-old female patient, born to a consanguineous Iranian family, was referred with various clinical symptoms including impaired speech, variable ataxia, infrequent seizures, and gradual onset of truncal hypotonia. Over time, she developed complete motor and speech regression, bilateral sensorineural hearing loss, infrequent seizures, abdominal distension and gastrointestinal (GI) intolerance, and loss of consciousness. To better molecularly diagnose, trio-whole-exome sequencing (WES) was performed on the proband and her parents. Sanger sequencing was also applied to investigate co-segregation analysis. Using in silico predictive tools, the possible impacts of the variant on the structure and function of ADPRHL2 protein were predicted. All basic metabolic tests were normal, while serial coronal magnetic resonance imaging (MRI) showed progressive cerebral and cerebellar atrophy in addition to cerebral white matter signal changes as a novel neuroimaging finding. GI intolerance was another novelty of clinical scenarios in the patient. An auditory brainstem response test showed a severe bilateral sensorineural hearing loss. An electroencephalogram also confirmed focal seizures. From the molecular perspective, a novel homozygous frameshift variant in the ADPRHL2 gene (NM_017825.2; c.636_639del, p.(Leu212fs)) was identified by WES. Conclusions: CONDSIAS is an ultra-rare neurodegenerative disorder. In the present study, we introduced extraneurological and neuroimaging findings of this disorder in a female child caused by a novel frameshift variation in the ADPRHL2 gene.

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ADP-ribosylation: from molecular mechanisms to human disease

Cited by 40 publications

References 162 publications

Signalling Network of Breast Cancer Cells in Response to Progesterone

Signalling Network of Breast Cancer Cells in Response to Progesterone

The Viral Macrodomain Counters Host Antiviral ADP-Ribosylation

Novel imaging and clinical phenotypes of CONDSIAS disorder caused by a homozygous frameshift variant of ADPRHL2: a case report

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