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dc.contributor.authorGomez, A.
dc.contributor.authorBindesboll, C.
dc.contributor.authorSatheesh, S.V.
dc.contributor.authorGrimaldi, Giulia
dc.contributor.authorHutin, D.
dc.contributor.authorMacPherson, L.
dc.contributor.authorAhmed, S.
dc.contributor.authorTamblyn, L.
dc.contributor.authorCho, T.
dc.contributor.authorNebb, H.I.
dc.contributor.authorMoen, A.
dc.contributor.authorAnonsen, J.H.
dc.contributor.authorGrant, D.M.
dc.contributor.authorMatthews, J.
dc.date.accessioned2021-02-08T12:25:55Z
dc.date.available2021-02-08T12:25:55Z
dc.date.issued2018-12
dc.identifier.citationGomez A, Bindesboll C, Satheesh SV et al (2018) Characterization of TCDD-inducible poly-ADP-ribose polymerase (TIPARP/ARTD14) catalytic activity. Biochemical Journal. 475(23): 3827-3846.en_US
dc.identifier.urihttp://hdl.handle.net/10454/18333
dc.descriptionYesen_US
dc.description.abstractHere, we report the biochemical characterization of the mono-ADP-ribosyltransferase 2,3,7,8-tetrachlorodibenzo-p-dioxin poly-ADP-ribose polymerase (TIPARP/ARTD14/PARP7), which is known to repress aryl hydrocarbon receptor (AHR)-dependent transcription. We found that the nuclear localization of TIPARP was dependent on a short N-terminal sequence and its zinc finger domain. Deletion and in vitro ADP-ribosylation studies identified amino acids 400–657 as the minimum catalytically active region, which retained its ability to mono-ADP-ribosylate AHR. However, the ability of TIPARP to ADP-ribosylate and repress AHR in cells was dependent on both its catalytic activity and zinc finger domain. The catalytic activity of TIPARP was resistant to meta-iodobenzylguanidine but sensitive to iodoacetamide and hydroxylamine, implicating cysteines and acidic side chains as ADP-ribosylated target residues. Mass spectrometry identified multiple ADP-ribosylated peptides in TIPARP and AHR. Electron transfer dissociation analysis of the TIPARP peptide 33ITPLKTCFK41 revealed cysteine 39 as a site for mono-ADP-ribosylation. Mutation of cysteine 39 to alanine resulted in a small, but significant, reduction in TIPARP autoribosylation activity, suggesting that additional amino acid residues are modified, but loss of cysteine 39 did not prevent its ability to repress AHR. Our findings characterize the subcellular localization and mono-ADP-ribosyltransferase activity of TIPARP, identify cysteine as a mono-ADP-ribosylated residue targeted by this enzyme, and confirm the TIPARP-dependent mono-ADP-ribosylation of other protein targets, such as AHR.en_US
dc.description.sponsorshipThis work was supported by Canadian Institutes of Health Research (CIHR) operating grants [MOP-494265 and MOP-125919]; CIHR New Investigator Award; an Early Researcher Award from the Ontario Ministry of Innovation [ER10-07-028]; the Johan Throne Holst Foundation; Novo Nordic Foundation; and the Norwegian Cancer Society to J.M. This work was also funded by grants from the Johan Throne Holst Foundation; and the Novo Nordic Foundation to H.I.N.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttps://doi.org/10.1042/BCJ20180347en_US
dc.rights© 2018 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY-NC-ND)en_US
dc.subjectAryl hydrocarbon receptoren_US
dc.subjectMass spectrometryen_US
dc.subjectMono-ADP-riboseen_US
dc.subjectPoly-ADP-ribose polymeraseen_US
dc.subjectTCDD-inducible poly-ADP-ribose polymeraseen_US
dc.titleCharacterization of TCDD-inducible poly-ADP-ribose polymerase (TIPARP/ARTD14) catalytic activityen_US
dc.status.refereedYesen_US
dc.date.Accepted2018-10-29
dc.date.application2018-10-29
dc.typeArticleen_US
dc.type.versionPublished versionen_US
refterms.dateFOA2021-02-08T12:26:39Z
dc.openaccess.statusGreenen_US


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