Identifying Family-Member-Specific Targets of Mono-ARTDs by Using a Chemical Genetics Approach

Carter-O’Connell, Ian; Jin, Haihong; Morgan, Rory K.; Žaja, Roko; David, Larry L.; Ahel, Ivan; Cohen, Michael S.

doi:10.1016/j.celrep.2015.12.045

Cited by 75 publications

(75 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, we expect this trend will be changed soon with the coming-of-age technologies to investigate enzyme–substrate specificity of 17 human ADP-ribosyltransferases. These include proteome arrays (18,19), the development of analog-sensitive ADP-ribosyltransferases (47–49) as well as the improvement in performing genetic knockdown by RNA interference and knockout using CRISPR in mammalian cell culture. Finally, PARP inhibition is actively used in clinical settings.…”

Section: Introductionmentioning

confidence: 99%

ADPriboDB: The database of ADP-ribosylated proteins

et al. 2016

View full text Add to dashboard Cite

ADP-ribosylation refers to the addition of one or more ADP-ribose units onto proteins post-translationally. This protein modification is often added by ADP-ribosyltransferases, commonly known as PARPs, but it can also be added by other enzymes, including sirtuins or bacterial toxins. While past literature has utilized a variety of methods to identify ADP-ribosylated proteins, recent proteomics studies bring the power of mass spectrometry to determine sites of the modification. To appreciate the diverse roles of ADP-ribosylation across the proteome, we have created ADPriboDB – a database of ADP-ribosylated proteins (http://ADPriboDB.leunglab.org). Each entry of ADPriboDB is annotated manually by at least two independent curators from the literature between January 1975 and July 2015. The current database includes over 12 400 protein entries from 459 publications, identifying 2389 unique proteins. Here, we describe the structure and the current state of ADPriboDB as well as the criteria for entry inclusion. Using this aggregate data, we identified a statistically significant enrichment of ADP-ribosylated proteins in non-membranous RNA granules. To our knowledge, ADPriboDB is the first publicly available database encapsulating ADP-ribosylated proteins identified from the past 40 years, with a hope to facilitate the research of both basic scientists and clinicians to better understand ADP-ribosylation at the molecular level.

show abstract

Section: Introductionmentioning

confidence: 99%

ADPriboDB: The database of ADP-ribosylated proteins

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Because these chemical linkages can be quite different, and many of the site identifications for PARPs appear to be dependent on the technique used to identify them, it is unclear which of the amino acids are the true sites of ADP-ribosylation in the cell. Combining recently developed strategies for finding the direct targets of MARylating PARPs with mass spectrometry methods to identify the aa-ADPr sites will help figure out the family-member-specific amino acid targeting preferences across multiple targets 50,76 . Indeed, a recent study combining a chemical–genetics strategy to identify targets of the nuclear PARPs (PARP1, PARP2, and PARP3) with a mass spectrometry method to identify aa-ADPr sites revealed potential family-member-specific consensus sequences 50 .…”

Section: Target Recognition and Amino Acid Selectionmentioning

confidence: 99%

Insights into the biogenesis, function, and regulation of ADP-ribosylation

2018

View full text Add to dashboard Cite

ADP-ribosylation—the transfer of ADP-ribose (ADPr) from NAD+ onto target molecules—is catalyzed by members of the ADP-ribosyltransferase (ART) superfamily of proteins, found in all kingdoms of life. Modification of amino acids in protein targets by ADPr regulates critical cellular pathways in eukaryotes and underlies the pathogenicity of certain bacteria. Several members of the ART superfamily are highly relevant for disease; these include the poly(ADP-ribose) polymerases (PARPs), recently shown to be important cancer targets, and the bacterial toxins diphtheria toxin and cholera toxin, long known to be responsible for the symptoms of diphtheria and cholera that result in morbidity. In this Review, we discuss the functions of amino acid ADPr modifications and the ART proteins that make them, the nature of the chemical linkage between ADPr and its targets and how this impacts function and stability, and the way that ARTs select specific amino acids in targets to modify.

show abstract

“…This is mainly due to the labile bonds between ADP-ribose to the substrate, and the low abundance of this modification in steady state conditions. So far, chemical tools, such as NAD+ analogues, have been used for in vitro approaches, (Carter-O'Connell et al, 2016). Monitoring PARylation has been possible in vitro using the PAR affinity resin (Tulip-4301 www.tulipbiolabs.com/4301.html) and monoclonal antibodies, such as 10H and LP96-10.…”

Section: Introductionmentioning

confidence: 99%

In vivo vizualisation of mono-ADP-ribosylation by dPARP16 upon amino-acid starvation

Aguilera-Gomez

Oorschot

Veenendaal

et al. 2016

eLife

View full text Add to dashboard Cite

PARP catalysed ADP-ribosylation is a post-translational modification involved in several physiological and pathological processes, including cellular stress. In order to visualise both Poly-, and Mono-, ADP-ribosylation in vivo, we engineered specific fluorescent probes. Using them, we show that amino-acid starvation triggers an unprecedented display of mono-ADP-ribosylation that governs the formation of Sec body, a recently identified stress assembly that forms in Drosophila cells. We show that dPARP16 catalytic activity is necessary and sufficient for both amino-acid starvation induced mono-ADP-ribosylation and subsequent Sec body formation and cell survival. Importantly, dPARP16 catalyses the modification of Sec16, a key Sec body component, and we show that it is a critical event for the formation of this stress assembly. Taken together our findings establish a novel example for the role of mono-ADP-ribosylation in the formation of stress assemblies, and link this modification to a metabolic stress.DOI: http://dx.doi.org/10.7554/eLife.21475.001

show abstract

Identifying Family-Member-Specific Targets of Mono-ARTDs by Using a Chemical Genetics Approach

Cited by 75 publications

References 27 publications

ADPriboDB: The database of ADP-ribosylated proteins

ADPriboDB: The database of ADP-ribosylated proteins

Insights into the biogenesis, function, and regulation of ADP-ribosylation

In vivo vizualisation of mono-ADP-ribosylation by dPARP16 upon amino-acid starvation

Contact Info

Product

Resources

About