{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T08:20:36Z","timestamp":1788337236932,"version":"build-2803163510"},"reference-count":42,"publisher":"American Chemical Society (ACS)","issue":"11","license":[{"start":{"date-parts":[[2015,6,16]],"date-time":"2015-06-16T00:00:00Z","timestamp":1434412800000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,11,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Members of the 2-aminobenzamide class of histone deacetylase (HDAC) inhibitors show promise as therapeutics for the neurodegenerative diseases Friedreich\u2019s ataxia (FRDA) and Huntington\u2019s disease (HD). While it is clear that HDAC3 is one of the important targets of the 2-aminobenzamide HDAC inhibitors, inhibition of other class I HDACs (HDACs 1 and 2) may also be involved in the beneficial effects of these compounds in FRDA and HD, and other HDAC interacting proteins may be impacted by the compound. To this end, we synthesized activity-based profiling probe (ABPP) versions of one of our HDAC inhibitors (compound 106), and in the present study we used a quantitative proteomic method coupled with multidimensional protein identification technology (MudPIT) to identify the proteins captured by the ABPP 106 probe. Nuclear proteins were extracted from FRDA patient iPSC-derived neural stem cells, and then were reacted with control and ABPP 106 probe. After reaction, the bound proteins were digested on the beads, and the peptides were modified using stable isotope-labeled formaldehyde to form dimethyl amine. The selectively bound proteins determined by mass spectrometry were subjected to functional and pathway analysis. Our findings suggest that the targets of compound 106 are involved not only in transcriptional regulation but also in posttranscriptional processing of mRNA.<\/jats:p>","DOI":"10.1021\/pr500514r","type":"journal-article","created":{"date-parts":[[2014,6,16]],"date-time":"2014-06-16T16:46:43Z","timestamp":1402937203000},"page":"4558-4566","source":"Crossref","is-referenced-by-count":28,"title":["Quantitative Proteomic Analysis Identifies Targets and Pathways of a 2-Aminobenzamide HDAC Inhibitor in Friedreich\u2019s Ataxia Patient iPSC-Derived Neural Stem Cells"],"prefix":"10.1021","volume":"13","author":[{"given":"Bing","family":"Shan","sequence":"first","affiliation":[{"name":"The Scripps Research Institute , , , ,","place":["La Jolla, California, United States, 92037"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunping","family":"Xu","sequence":"additional","affiliation":[{"name":"The Scripps Research Institute , , , ,","place":["La Jolla, California, United States, 92037"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Scripps Research Institute , , , ,","place":["La Jolla, California, United States, 92037"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Xu","sequence":"additional","affiliation":[{"name":"The Scripps Research Institute , , , ,","place":["La Jolla, California, United States, 92037"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel M.","family":"Gottesfeld","sequence":"additional","affiliation":[{"name":"The Scripps Research Institute , , , ,","place":["La Jolla, California, United States, 92037"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"John R.","family":"Yates","sequence":"additional","affiliation":[{"name":"The Scripps Research Institute , , , ,","place":["La Jolla, California, United States, 92037"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,6,16]]},"reference":[{"issue":"Suppl 1","key":"2026090203574634100_cit1","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1111\/jnc.12302","article-title":"Increasing\nfrataxin gene expression with histone deacetylase inhibitors as a\ntherapeutic approach for Friedreich\u2019s ataxia","volume":"126","author":"Gottesfeld","year":"2013","journal-title":"J. Neurochem"},{"issue":"24","key":"2026090203574634100_cit2","doi-asserted-by":"crossref","first-page":"5280","DOI":"10.1093\/hmg\/dds379","article-title":"Selective histone\ndeacetylase (HDAC) inhibition imparts beneficial effects in Huntington\u2019s\ndisease mice: implications for the ubiquitin-proteasomal and autophagy\nsystems","volume":"21","author":"Jia","year":"2012","journal-title":"Hum. Mol. Genet."},{"issue":"2","key":"2026090203574634100_cit3","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.nbd.2012.01.016","article-title":"Histone\ndeacetylase (HDAC) inhibitors targeting HDAC3 and HDAC1 ameliorate\npolyglutamine-elicited phenotypes in model systems of Huntington\u2019s\ndisease","volume":"46","author":"Jia","year":"2012","journal-title":"Neurobiol. Dis."},{"issue":"3","key":"2026090203574634100_cit4","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S1071-9091(03)00025-1","article-title":"Friedreich ataxia","volume":"10","author":"Pandolfo","year":"2003","journal-title":"Semin. Pediatr. Neurol."},{"issue":"10","key":"2026090203574634100_cit5","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/nchembio815","article-title":"Histone deacetylase inhibitors reverse gene silencing\nin Friedreich\u2019s ataxia","volume":"2","author":"Herman","year":"2006","journal-title":"Nat. Chem. Biol."},{"issue":"51","key":"2026090203574634100_cit6","doi-asserted-by":"crossref","first-page":"35402","DOI":"10.1074\/jbc.M807045200","article-title":"Pimelic\ndiphenylamide 106 is a slow, tight-binding inhibitor of class I histone\ndeacetylases","volume":"283","author":"Chou","year":"2008","journal-title":"J. Biol. Chem."},{"issue":"9","key":"2026090203574634100_cit7","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1016\/j.chembiol.2009.07.010","article-title":"Chemical\nprobes identify a role for histone deacetylase 3 in Friedreich\u2019s\nataxia gene silencing","volume":"16","author":"Xu","year":"2009","journal-title":"Chem. Biol."},{"issue":"4","key":"2026090203574634100_cit8","doi-asserted-by":"crossref","first-page":"e1958","DOI":"10.1371\/journal.pone.0001958","article-title":"HDAC inhibitors correct frataxin\ndeficiency in a Friedreich ataxia mouse model","volume":"3","author":"Rai","year":"2008","journal-title":"PLoS One"},{"issue":"1","key":"2026090203574634100_cit9","doi-asserted-by":"crossref","first-page":"e8825","DOI":"10.1371\/journal.pone.0008825","article-title":"Two new pimelic diphenylamide HDAC inhibitors induce\nsustained frataxin upregulation in cells from Friedreich\u2019s\nataxia patients and in a mouse model","volume":"5","author":"Rai","year":"2010","journal-title":"PLoS One"},{"issue":"3","key":"2026090203574634100_cit10","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.nbd.2011.02.016","article-title":"Prolonged treatment with pimelic\no-aminobenzamide HDAC inhibitors ameliorates the disease phenotype\nof a Friedreich ataxia mouse model","volume":"42","author":"Sandi","year":"2011","journal-title":"Neurobiol.\nDis."},{"key":"2026090203574634100_cit11","unstructured":"Soragni, E.; et al., Epigenetic therapy for Friedreich\u2019s ataxia: Evaluation in\npatient iPSC-derived neuronal cells and in a Phase I clinical trial. 5th Ataxia Investigators Meeting (AIM), Las Vegas, NV, March 18\u201321, 2014."},{"issue":"10","key":"2026090203574634100_cit12","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1038\/nrd2681","article-title":"Therapeutic application of histone deacetylase inhibitors\nfor central nervous system disorders","volume":"7","author":"Kazantsev","year":"2008","journal-title":"Nat. Rev.\nDrug Discovery"},{"issue":"40","key":"2026090203574634100_cit13","doi-asserted-by":"crossref","first-page":"15564","DOI":"10.1073\/pnas.0804249105","article-title":"The HDAC inhibitor 4b ameliorates the disease phenotype\nand transcriptional abnormalities in Huntington\u2019s disease transgenic\nmice","volume":"105","author":"Thomas","year":"2008","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"issue":"6","key":"2026090203574634100_cit14","doi-asserted-by":"crossref","first-page":"505","DOI":"10.2174\/138161208783885353","article-title":"Chemical\norigins of isoform selectivity in histone deacetylase inhibitors","volume":"14","author":"Butler","year":"2008","journal-title":"Curr. Pharm. 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Proteome Res."},{"issue":"4","key":"2026090203574634100_cit21","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/nmeth.1195","article-title":"A quantitative analysis software tool for mass spectrometry-based\nproteomics","volume":"5","author":"Park","year":"2008","journal-title":"Nat. Methods"},{"issue":"1","key":"2026090203574634100_cit22","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic\nand integrative analysis of large gene lists using DAVID bioinformatics\nresources","volume":"4","author":"Huang da","year":"2009","journal-title":"Nat. Protoc."},{"issue":"10","key":"2026090203574634100_cit23","first-page":"1455","article-title":"VDR-Alien: a novel,\nDNA-selective vitamin D(3) receptor-corepressor partnership","volume":"14","author":"Polly","year":"2000","journal-title":"FASEB J."},{"issue":"1","key":"2026090203574634100_cit24","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1093\/nar\/gks959","article-title":"Chromatin acetylation at transcription\nstart sites and vitamin D receptor binding regions relates to effects\nof 1alpha,25-dihydroxyvitamin D3 and histone deacetylase inhibitors\non gene expression","volume":"41","author":"Seuter","year":"2013","journal-title":"Nucleic Acids Res."},{"issue":"20","key":"2026090203574634100_cit25","doi-asserted-by":"crossref","first-page":"9612","DOI":"10.1073\/pnas.89.20.9612","article-title":"A fraction\nof the mRNA 5\u2032 cap-binding protein, eukaryotic initiation factor\n4E, localizes to the nucleus","volume":"89","author":"Lejbkowicz","year":"1992","journal-title":"Proc. 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Biochem.\nCell Biol."},{"issue":"6","key":"2026090203574634100_cit28","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1023\/A:1026455421490","article-title":"Localization\nof eukaryotic initiation factor 2 in neuron primary cultures and established\ncell lines","volume":"29","author":"Lobo","year":"1997","journal-title":"Histochem. J."},{"issue":"3","key":"2026090203574634100_cit29","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.ajpath.2013.05.032","article-title":"Molecular\nand functional alterations in a mouse cardiac model of Friedreich\nataxia: activation of the integrated stress response, eIF2alpha phosphorylation,\nand the induction of downstream targets","volume":"183","author":"Huang","year":"2013","journal-title":"Am.\nJ. Pathol."},{"issue":"5","key":"2026090203574634100_cit30","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1002\/ana.22526","article-title":"A gene expression phenotype in lymphocytes\nfrom Friedreich ataxia patients","volume":"70","author":"Coppola","year":"2011","journal-title":"Ann. Neurol."},{"issue":"Suppl 1","key":"2026090203574634100_cit31","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/jnc.12254","article-title":"Gene regulation and epigenetics in Friedreich\u2019s\nataxia","volume":"126","author":"Yandim","year":"2013","journal-title":"J. Neurochem."},{"issue":"4","key":"2026090203574634100_cit32","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1073\/pnas.0608659104","article-title":"Activity-based probes\nfor proteomic profiling of histone deacetylase complexes","volume":"104","author":"Salisbury","year":"2007","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"issue":"3","key":"2026090203574634100_cit33","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/nbt.1759","article-title":"Chemoproteomics\nprofiling of HDAC inhibitors reveals selective targeting of HDAC complexes","volume":"29","author":"Bantscheff","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"2026090203574634100_cit34","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1038\/msb.2013.26","article-title":"The functional interactome landscape\nof the human histone deacetylase family","volume":"9","author":"Joshi","year":"2013","journal-title":"Mol.\nSyst. Biol."},{"issue":"6934","key":"2026090203574634100_cit35","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1038\/nature01596","article-title":"DNA triplet repeats mediate heterochromatin-protein-1-sensitive\nvariegated gene silencing","volume":"422","author":"Saveliev","year":"2003","journal-title":"Nature"},{"issue":"2","key":"2026090203574634100_cit36","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.molcel.2012.11.011","article-title":"A SWI\/SNF chromatin-remodeling complex acts in noncoding\nRNA-mediated transcriptional silencing","volume":"49","author":"Zhu","year":"2013","journal-title":"Mol.\nCell"},{"issue":"41","key":"2026090203574634100_cit37","doi-asserted-by":"crossref","first-page":"16520","DOI":"10.1073\/pnas.1315803110","article-title":"Core small nuclear ribonucleoprotein particle splicing factor SmD1\nmodulates RNA interference in Drosophila","volume":"110","author":"Xiong","year":"2013","journal-title":"Proc.\nNatl. Acad. Sci. U.S.A."},{"issue":"Pt 1","key":"2026090203574634100_cit38","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1042\/BST0340022","article-title":"The large spectrum of eIF2B-related\ndiseases","volume":"34","author":"Fogli","year":"2006","journal-title":"Biochem. Soc. Trans."},{"issue":"21","key":"2026090203574634100_cit39","doi-asserted-by":"crossref","first-page":"2526","DOI":"10.1101\/gad.1348805","article-title":"Lost in translation:\nthe influence of ribosomes on bacterial mRNA decay","volume":"19","author":"Deana","year":"2005","journal-title":"Genes Dev."},{"issue":"3","key":"2026090203574634100_cit40","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1128\/mr.59.3.423-450.1995","article-title":"mRNA stability\nin mammalian cells","volume":"59","author":"Ross","year":"1995","journal-title":"Microbiol. 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Chem."}],"container-title":["Journal of Proteome Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/pr500514r","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/13\/11\/4558\/13545551\/pr500514r.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/13\/11\/4558\/13545551\/pr500514r.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T07:57:59Z","timestamp":1788335879000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jprobs\/article\/13\/11\/4558\/1339697\/Quantitative-Proteomic-Analysis-Identifies-Targets"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,6,16]]},"references-count":42,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2014,6,16]]},"published-print":{"date-parts":[[2014,11,7]]}},"URL":"https:\/\/doi.org\/10.1021\/pr500514r","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718451483.793496533","asserted-by":"object"}]},"ISSN":["1535-3893","1535-3907"],"issn-type":[{"value":"1535-3893","type":"print"},{"value":"1535-3907","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,6,16]]}}}