PARP-10, a novel Myc-interacting protein with poly(ADP-ribose) polymerase activity, inhibits transformation

Yu, Mei; Schreek, Sabine; Cerni, Christa; Schamberger, Chantal; Leśniewicz, Krzysztof; Poręba, Elżbieta; Vervoorts, Jörg; Walsemann, Gesa; Grötzinger, Joachim; Kremmer, Elisabeth; Mehraein, Yasmin; Mertsching, Jürgen; Kraft, Regine; Austen, Matthias; Lüscher-Firzlaff, Juliane; Lüscher, Bernhard

doi:10.1038/sj.onc.1208410

Cited by 135 publications

(170 citation statements)

References 75 publications

(82 reference statements)

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“…Several protein domains with possible functional relevance have been identified in ARTD10 (ref. 2). Unique among the ARTD family members are two UIMs in the C terminal half of ARTD10 (Fig.…”

Section: Artd10mentioning

confidence: 99%

“…Unique among the ARTD family members are two UIMs in the C terminal half of ARTD10 (Fig. 1a,b) 2,11,12 . They are functional because GST-ARTD10(600-868), containing both UIMs, bound K63-pUb that was at least tetrameric (Fig.…”

Section: Artd10mentioning

confidence: 99%

“…A RTD10 (formerly PARP10) 1 , originally identified as a MYC-interacting protein, possesses mono-adenosine diphosphate (ADP)-ribosyltransferase activity 2,3 . The ARTD family consists of 18 members.…”

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confidence: 99%

“…ARTD10 is capable of mono-ADP-ribosylating itself and core histones 2,3 , but its biological relevance remains undefined. Within the ARTD family, ARTD10 is the only member with two ubiquitin-interaction motifs (UIMs).…”

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confidence: 99%

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Regulation of NF-κB signalling by the mono-ADP-ribosyltransferase ARTD10

et al. 2013

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Adenosine diphosphate-ribosylation is a post-translational modification mediated by intracellular and membrane-associated extracellular enzymes and many bacterial toxins. The intracellular enzymes modify their substrates either by poly-ADP-ribosylation, exemplified by ARTD1/PARP1, or by mono-ADP-ribosylation. The latter has been discovered only recently, and little is known about its physiological relevance. The founding member of mono-ADPribosyltransferases is ARTD10/PARP10. It possesses two ubiquitin-interaction motifs, a unique feature among ARTD/PARP enzymes. Here, we find that the ARTD10 ubiquitininteraction motifs bind to K63-linked poly-ubiquitin, a modification that is essential for NF-kB signalling. We therefore studied the role of ARTD10 in this pathway. ARTD10 inhibits the activation of NF-kB and downstream target genes in response to interleukin-1b and tumour necrosis factor-a, dependent on catalytic activity and poly-ubiquitin binding of ARTD10. Mechanistically ARTD10 interferes with poly-ubiquitination of NEMO, which interacts with and is a substrate of ARTD10. Our findings identify a novel regulator of NF-kB signalling and provide evidence for cross-talk between K63-linked poly-ubiquitination and mono-ADPribosylation.

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Section: Artd10mentioning

confidence: 99%

Section: Artd10mentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Regulation of NF-κB signalling by the mono-ADP-ribosyltransferase ARTD10

et al. 2013

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“…ARTD10 was first identified as a binding partner of the oncoprotein c-Myc and it was the first member of the ARTD family to be fully characterized as an mARTD (Kleine et al, 2008). ARTD10 has a conserved C-terminal ART domain responsible for its enzymatic activity (Hottiger et al, 2010;Kleine et al, 2008;Otto et al, 2005;Yu et al, 2005). In vitro screening of more than 8000 proteins identified 78 substrates for ARTD10 (Feijs et al, 2013a), the majority of these being kinases.…”

Section: Introductionmentioning

confidence: 99%

Small-Molecule Chemical Probe Rescues Cells from Mono-ADP-Ribosyltransferase ARTD10/PARP10-Induced Apoptosis and Sensitizes Cancer Cells to DNA Damage

Venkannagari

Verheugd

Koivunen

et al. 2016

Cell Chemical Biology

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SUMMARYMembers of the human diphtheria toxin-likeADP-ribosyltransferase (ARTD or PARP) family play important roles in regulating biological activities by mediating either a mono-ADP-ribosylation MARylation) of a substrate or a poly-ADP-ribosylation (PARylation). ARTD10/PARP10 belongs to the MARylating ARTDs (mARTDs) subfamily, and plays important roles in biological processes that range from cellular signaling, DNA repair, and cell proliferation to immune response. Despite their biological and disease relevance, no selective inhibitors for mARTDs are available. Here we describe a small-molecule ARTD10 inhibitor, OUL35, a selective and potent inhibitor for this enzyme. We characterize its selectivity profile, model its binding, and demonstrate activity in HeLa cells where OUL35 rescued cells from ARTD10 induced cell death. Using OUL35 as a cell biology tool we show that ARTD10 inhibition sensitizes the cells to the hydroxyurea-induced genotoxic stress. Our study supports the proposed role of ARTD10 in DNA-damage repair and provides a tool compound for selective inhibition of ARTD10-mediated MARylation.3

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