{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T16:21:00Z","timestamp":1772641260606,"version":"3.50.1"},"reference-count":77,"publisher":"The Company of Biologists","issue":"11","license":[{"start":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T00:00:00Z","timestamp":1667174400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Facioscapulohumeral muscular dystrophy (FSHD) is caused by misexpression of the DUX4 transcription factor in skeletal muscle that results in transcriptional alterations, abnormal phenotypes and cell death. To gain insight into the kinetics of DUX4-induced stresses, we activated DUX4 expression in myoblasts and performed longitudinal RNA sequencing paired with proteomics and phosphoproteomics. This analysis revealed changes in cellular physiology upon DUX4 activation, including DNA damage and altered mRNA splicing. Phosphoproteomic analysis uncovered rapid widespread changes in protein phosphorylation following DUX4 induction, indicating that alterations in kinase signaling might play a role in DUX4-mediated stress and cell death. Indeed, we demonstrate that two stress-responsive MAP kinase pathways, JNK and p38, are activated in response to DUX4 expression. Inhibition of each of these pathways ameliorated DUX4-mediated cell death in myoblasts. These findings uncover that the JNK pathway is involved in DUX4-mediated cell death and provide additional insights into the role of the p38 pathway, a clinical target for the treatment of FSHD.<\/jats:p>","DOI":"10.1242\/dmm.049516","type":"journal-article","created":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T08:21:17Z","timestamp":1664958077000},"source":"Crossref","is-referenced-by-count":14,"title":["DUX4 expression activates JNK and p38 MAP kinases in myoblasts"],"prefix":"10.1242","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4023-6056","authenticated-orcid":false,"given":"Christopher M.","family":"Brennan","sequence":"first","affiliation":[{"name":"Pfizer Inc. 1 Rare Disease Research Unit , , Cambridge, MA 02139 , USA"},{"name":"Pfizer Inc. 2 WRDM Postdoctoral Program , , Cambridge, MA 02139 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abby S.","family":"Hill","sequence":"additional","affiliation":[{"name":"Pfizer Inc. 1 Rare Disease Research Unit , , Cambridge, MA 02139 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"St. Andre","sequence":"additional","affiliation":[{"name":"Pfizer Inc. 1 Rare Disease Research Unit , , Cambridge, MA 02139 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianfeng","family":"Li","sequence":"additional","affiliation":[{"name":"Pfizer Inc. 1 Rare Disease Research Unit , , Cambridge, MA 02139 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vijaya","family":"Madeti","sequence":"additional","affiliation":[{"name":"NGS Technology Center 3 , Inflammation and Immunology Research Unit , , Cambridge, MA 02139 , USA"},{"name":"Pfizer 3 , Inflammation and Immunology Research Unit , , Cambridge, MA 02139 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Breitkopf","sequence":"additional","affiliation":[{"name":"Proteomics Technology Center 4 , Internal Medicine Research Unit , , Cambridge, MA 02139 , USA"},{"name":"Pfizer 4 , Internal Medicine Research Unit , , Cambridge, MA 02139 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seth","family":"Garren","sequence":"additional","affiliation":[{"name":"NGS Technology Center 3 , Inflammation and Immunology Research Unit , , Cambridge, MA 02139 , USA"},{"name":"Pfizer 3 , Inflammation and Immunology Research Unit , , Cambridge, MA 02139 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Xue","sequence":"additional","affiliation":[{"name":"Pfizer Inc. 5 Machine Learning and Computational Science , , Cambridge, MA 02139 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamara","family":"Gilbert","sequence":"additional","affiliation":[{"name":"High Content Imaging Technology Center 6 , Internal Medicine Research Unit , , Cambridge, MA 02139 , USA"},{"name":"Pfizer 6 , Internal Medicine Research Unit , , Cambridge, MA 02139 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Hadjipanayis","sequence":"additional","affiliation":[{"name":"NGS Technology Center 3 , Inflammation and Immunology Research Unit , , Cambridge, MA 02139 , USA"},{"name":"Pfizer 3 , Inflammation and Immunology Research Unit , , Cambridge, MA 02139 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mara","family":"Monetti","sequence":"additional","affiliation":[{"name":"Proteomics Technology Center 4 , Internal Medicine Research Unit , , Cambridge, MA 02139 , USA"},{"name":"Pfizer 4 , Internal Medicine Research Unit , , Cambridge, MA 02139 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr","given":"Charles P.","family":"Emerson","sequence":"additional","affiliation":[{"name":"Pfizer Inc. 1 Rare Disease Research Unit , , Cambridge, MA 02139 , USA"},{"name":"University of Massachusetts Medical School 7 Wellstone Muscular Dystrophy Program, Department of Neurology , , Worcester, MA 01655 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Moccia","sequence":"additional","affiliation":[{"name":"Pfizer Inc. 1 Rare Disease Research Unit , , Cambridge, MA 02139 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane","family":"Owens","sequence":"additional","affiliation":[{"name":"Pfizer Inc. 1 Rare Disease Research Unit , , Cambridge, MA 02139 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4594-6919","authenticated-orcid":false,"given":"Nicolas","family":"Christoforou","sequence":"additional","affiliation":[{"name":"Pfizer Inc. 1 Rare Disease Research Unit , , Cambridge, MA 02139 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2022,10,31]]},"reference":[{"key":"2022103110523701200_DMM049516C1","doi-asserted-by":"publisher","first-page":"R106","DOI":"10.1186\/gb-2010-11-10-r106","article-title":"Differential expression analysis for sequence count data","volume":"11","author":"Anders","year":"2010","journal-title":"Genome Biol."},{"key":"2022103110523701200_DMM049516C2","doi-asserted-by":"publisher","first-page":"13681","DOI":"10.1073\/pnas.251194298","article-title":"SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase","volume":"98","author":"Bennett","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2022103110523701200_DMM049516C3","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.bbapap.2003.11.016","article-title":"Targeting the JNK MAPK cascade for inhibition: basic science and therapeutic potential","volume":"1697","author":"Bogoyevitch","year":"2004","journal-title":"Biochim. Biophys. Acta Proteins Proteom."},{"key":"2022103110523701200_DMM049516C4","doi-asserted-by":"publisher","first-page":"1668","DOI":"10.1152\/jappl.1999.87.5.1668","article-title":"Eccentric exercise markedly increases c-Jun NH2-terminal kinase activity in human skeletal muscle","volume":"87","author":"Boppart","year":"1999","journal-title":"J. Appl. Physiol."},{"key":"2022103110523701200_DMM049516C5","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1038\/s41467-017-00730-1","article-title":"Muscle pathology from stochastic low level DUX4 expression in an FSHD mouse model","volume":"8","author":"Bosnakovski","year":"2017","journal-title":"Nat. Commun."},{"key":"2022103110523701200_DMM049516C6","doi-asserted-by":"publisher","first-page":"1969","DOI":"10.1101\/gad.1107303","article-title":"Mechanism of p38 MAP kinase activation in vivo","volume":"17","author":"Brancho","year":"2003","journal-title":"Gene Dev."},{"key":"2022103110523701200_DMM049516C7","doi-asserted-by":"publisher","first-page":"e149915","DOI":"10.1172\/jci.insight.149915","article-title":"p38 MAPKs \u2014 roles in skeletal muscle physiology, disease mechanisms, and as potential therapeutic targets","volume":"6","author":"Brennan","year":"2021","journal-title":"JCI Insight"},{"key":"2022103110523701200_DMM049516C8","doi-asserted-by":"publisher","first-page":"R153","DOI":"10.1093\/hmg\/ddy162","article-title":"Facioscapulohumeral dystrophy: activating an early embryonic transcriptional program in human skeletal muscle","volume":"27","author":"Campbell","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"2022103110523701200_DMM049516C9","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1128\/MMBR.00031-10","article-title":"Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases","volume":"75","author":"Cargnello","year":"2011","journal-title":"Microbiol. Mol. Biol. R"},{"key":"2022103110523701200_DMM049516C10","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1016\/S1074-7613(00)80146-6","article-title":"JNK2 and IKK\u03b2 are required for activating the innate response to viral infection","volume":"11","author":"Chu","year":"1999","journal-title":"Immunity"},{"key":"2022103110523701200_DMM049516C11","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1042\/BJ20100323","article-title":"Mechanisms and functions of p38 MAPK signalling","volume":"429","author":"Cuadrado","year":"2010","journal-title":"Biochem. J."},{"key":"2022103110523701200_DMM049516C12","doi-asserted-by":"publisher","first-page":"1358","DOI":"10.1016\/j.bbamcr.2007.03.010","article-title":"p38 MAP-kinases pathway regulation, function and role in human diseases","volume":"1773","author":"Cuenda","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"2022103110523701200_DMM049516C13","doi-asserted-by":"publisher","first-page":"3159","DOI":"10.1038\/sj.onc.1210409","article-title":"Role of mitogen-activated protein kinase kinase kinases in signal integration","volume":"26","author":"Cuevas","year":"2007","journal-title":"Oncogene"},{"key":"2022103110523701200_DMM049516C14","doi-asserted-by":"publisher","first-page":"e0160022","DOI":"10.1371\/journal.pone.0160022","article-title":"Influence of repressive histone and DNA methylation upon D4Z4 transcription in non-myogenic cells","volume":"11","author":"Das","year":"2016","journal-title":"PLoS ONE"},{"key":"2022103110523701200_DMM049516C15","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1016\/0092-8674(94)90380-8","article-title":"JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain","volume":"76","author":"D\u00e9rijard","year":"1994","journal-title":"Cell"},{"key":"2022103110523701200_DMM049516C16","doi-asserted-by":"publisher","first-page":"6245","DOI":"10.1038\/onc.2008.301","article-title":"JNK signaling in apoptosis","volume":"27","author":"Dhanasekaran","year":"2008","journal-title":"Oncogene"},{"key":"2022103110523701200_DMM049516C17","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.freeradbiomed.2016.08.007","article-title":"DUX4-induced constitutive DNA damage and oxidative stress contribute to aberrant differentiation of myoblasts from FSHD patients","volume":"99","author":"Dmitriev","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"2022103110523701200_DMM049516C18","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"2022103110523701200_DMM049516C19","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1038\/35011091","article-title":"JNK is required for effector T-cell function but not for T-cell activation","volume":"405","author":"Dong","year":"2000","journal-title":"Nature"},{"key":"2022103110523701200_DMM049516C74","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1016\/1044-0305(94)80016-2","article-title":"An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database","volume":"5","author":"Eng","year":"1994","journal-title":"J Am. Soc. Mass Spectrom."},{"key":"2022103110523701200_DMM049516C20","doi-asserted-by":"publisher","first-page":"e04996","DOI":"10.7554\/eLife.04996","article-title":"A feedback loop between nonsense-mediated decay and the retrogene DUX4 in facioscapulohumeral muscular dystrophy","volume":"4","author":"Feng","year":"2015","journal-title":"eLife"},{"key":"2022103110523701200_DMM049516C21","doi-asserted-by":"publisher","first-page":"10541","DOI":"10.1073\/pnas.95.18.10541","article-title":"MEKK1\/JNK signaling stabilizes and activates p53","volume":"95","author":"Fuchs","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2022103110523701200_DMM049516C22","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.devcel.2011.11.013","article-title":"DUX4 activates germline genes, retroelements, and immune mediators: implications for facioscapulohumeral dystrophy","volume":"22","author":"Geng","year":"2012","journal-title":"Dev. Cell"},{"key":"2022103110523701200_DMM049516C23","doi-asserted-by":"publisher","first-page":"10442","DOI":"10.1074\/jbc.M311129200","article-title":"Activation of apoptosis signal-regulating kinase 1 by reactive oxygen species through dephosphorylation at serine 967 and 14-3-3 dissociation","volume":"279","author":"Goldman","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2022103110523701200_DMM049516C24","doi-asserted-by":"publisher","first-page":"1449","DOI":"10.1002\/humu.21091","article-title":"Common epigenetic changes of D4Z4 in contraction-dependent and contraction-independent FSHD","volume":"30","author":"Greef","year":"2009","journal-title":"Hum. Mutat."},{"key":"2022103110523701200_DMM049516C25","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1038\/ng.3844","article-title":"Conserved roles for murine DUX and human DUX4 in activating cleavage stage genes and MERVL\/HERVL retrotransposons","volume":"49","author":"Hendrickson","year":"2017","journal-title":"Nat. Genet."},{"key":"2022103110523701200_DMM049516C26","doi-asserted-by":"publisher","first-page":"2135","DOI":"10.1101\/gad.7.11.2135","article-title":"Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain","volume":"7","author":"Hibi","year":"1993","journal-title":"Gene Dev."},{"key":"2022103110523701200_DMM049516C77","doi-asserted-by":"publisher","DOI":"10.5061\/dryad.k0p2ngfbh","article-title":"Data from: DUX4 expression activates JNK and p38 MAP kinases in myoblasts","author":"Hill","year":"2022","journal-title":"Dryad Digital Repository."},{"key":"2022103110523701200_DMM049516C27","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1002\/acn3.158","article-title":"Expression of FSHD-related DUX4-FL alters proteostasis and induces TDP-43 aggregation","volume":"2","author":"Homma","year":"2015","journal-title":"Annal. Clin. Transl. Neurol."},{"key":"2022103110523701200_DMM049516C28","doi-asserted-by":"publisher","first-page":"1706","DOI":"10.1074\/mcp.RA120.002105","article-title":"MSstatsTMT: statistical detection of differentially abundant proteins in experiments with isobaric labeling and multiple mixtures","volume":"19","author":"Huang","year":"2020","journal-title":"Mol. Cell. Proteomics"},{"key":"2022103110523701200_DMM049516C29","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1038\/ng.3858","article-title":"DUX-family transcription factors regulate zygotic genome activation in placental mammals","volume":"49","author":"Iaco","year":"2017","journal-title":"Nat. Genet."},{"key":"2022103110523701200_DMM049516C30","doi-asserted-by":"publisher","first-page":"4419","DOI":"10.1093\/hmg\/ddw271","article-title":"Model systems of DUX4 expression recapitulate the transcriptional profile of FSHD cells","volume":"25","author":"Jagannathan","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"2022103110523701200_DMM049516C31","doi-asserted-by":"publisher","first-page":"20140797","DOI":"10.7554\/eLife.41740","article-title":"Quantitative proteomics reveals key roles for post-transcriptional gene regulation in the molecular pathology of facioscapulohumeral muscular dystrophy","volume":"8","author":"Jagannathan","year":"2019","journal-title":"eLife"},{"key":"2022103110523701200_DMM049516C32","doi-asserted-by":"publisher","first-page":"1341","DOI":"10.1016\/j.bbamcr.2006.12.009","article-title":"The c-jun kinase\/stress-activated pathway: regulation, function and role in human disease","volume":"1773","author":"Johnson","year":"2007","journal-title":"Biochim. Biophys. Acta Mol Cell Res."},{"key":"2022103110523701200_DMM049516C33","doi-asserted-by":"publisher","first-page":"e0192657","DOI":"10.1371\/journal.pone.0192657","article-title":"A cre-inducible DUX4 transgenic mouse model for investigating facioscapulohumeral muscular dystrophy","volume":"13","author":"Jones","year":"2018","journal-title":"PLoS ONE"},{"key":"2022103110523701200_DMM049516C34","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s13395-020-00227-4","article-title":"Transgenic mice expressing tunable levels of DUX4 develop characteristic facioscapulohumeral muscular dystrophy-like pathophysiology ranging in severity","volume":"10","author":"Jones","year":"2020","journal-title":"Skelet. Muscle"},{"key":"2022103110523701200_DMM049516C73","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1038\/nmeth1113","article-title":"Semi-supervised learning for peptide identification from shotgun proteomics datasets","volume":"4","author":"K\u00e4ll","year":"2007","journal-title":"Nat. Methods"},{"key":"2022103110523701200_DMM049516C35","doi-asserted-by":"publisher","first-page":"102008","DOI":"10.1016\/j.redox.2021.102008","article-title":"Analysis of genes regulated by DUX4 via oxidative stress reveals potential therapeutic targets for treatment of facioscapulohumeral dystrophy","volume":"43","author":"Karpukhina","year":"2021","journal-title":"Redox. Biol."},{"key":"2022103110523701200_DMM049516C36","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/978-1-60761-795-2_1","article-title":"MAP kinase signaling protocols, Second Edition","volume":"661","author":"Keshet","year":"2010","journal-title":"Methods Mol. Biol."},{"key":"2022103110523701200_DMM049516C37","doi-asserted-by":"publisher","first-page":"060012","DOI":"10.1101\/060012","article-title":"Fast gene set enrichment analysis","author":"Korotkevich","year":"2021","journal-title":"bioRxiv"},{"key":"2022103110523701200_DMM049516C38","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1016\/S0896-6273(00)80727-8","article-title":"The Jnk1 and Jnk2 protein kinases are required for regional specific apoptosis during early brain development","volume":"22","author":"Kuan","year":"1999","journal-title":"Neuron"},{"key":"2022103110523701200_DMM049516C39","first-page":"305","article-title":"Gamma-H2AX - a novel biomarker for DNA double-strand breaks","volume":"22","author":"Kuo","year":"2008","journal-title":"Vivo Athens Greece"},{"key":"2022103110523701200_DMM049516C40","doi-asserted-by":"publisher","first-page":"L930","DOI":"10.1152\/ajplung.1997.273.5.L930","article-title":"Phosphorylation of the 27-kDa heat shock protein via p38 MAP kinase and MAPKAP kinase in smooth muscle","volume":"273","author":"Larsen","year":"1997","journal-title":"Am. J. Physiol. Lung C"},{"key":"2022103110523701200_DMM049516C41","doi-asserted-by":"publisher","first-page":"R29","DOI":"10.1186\/gb-2014-15-2-r29","article-title":"voom: precision weights unlock linear model analysis tools for RNA-seq read counts","volume":"15","author":"Law","year":"2014","journal-title":"Genome Biol."},{"key":"2022103110523701200_DMM049516C42","doi-asserted-by":"publisher","first-page":"1650","DOI":"10.1126\/science.1189044","article-title":"A unifying genetic model for facioscapulohumeral muscular dystrophy","volume":"329","author":"Lemmers","year":"2010","journal-title":"Science (New York, N.Y.)"},{"key":"2022103110523701200_DMM049516C43","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.1038\/ng.2454","article-title":"Digenic inheritance of an SMCHD1 mutation and an FSHD-permissive D4Z4 allele causes facioscapulohumeral muscular dystrophy type 2","volume":"44","author":"Lemmers","year":"2012","journal-title":"Nat. Genet."},{"key":"2022103110523701200_DMM049516C44","doi-asserted-by":"publisher","first-page":"3030","DOI":"10.1038\/s41467-018-05439-3","article-title":"JNK regulates muscle remodeling via myostatin\/SMAD inhibition","volume":"9","author":"Lessard","year":"2018","journal-title":"Nat. Commun."},{"key":"2022103110523701200_DMM049516C45","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1042\/BJ20081501","article-title":"The SR protein family of splicing factors: master regulators of gene expression","volume":"417","author":"Long","year":"2008","journal-title":"Biochem. J."},{"key":"2022103110523701200_DMM049516C46","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1038\/nrd1132","article-title":"Targeting JNK for therapeutic benefit: from junk to gold?","volume":"2","author":"Manning","year":"2003","journal-title":"Nat. Rev. Drug Discov."},{"key":"2022103110523701200_DMM049516C47","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1016\/j.chembiol.2014.09.007","article-title":"Recent progress in the design, study, and development of c-Jun N-terminal kinase inhibitors as anticancer agents","volume":"21","author":"Messoussi","year":"2014","journal-title":"Chem. Biol."},{"key":"2022103110523701200_DMM049516C48","doi-asserted-by":"publisher","first-page":"a011254","DOI":"10.1101\/cshperspect.a011254","article-title":"MAP kinase pathways","volume":"4","author":"Morrison","year":"2012","journal-title":"Cold Spring Harbor Perspect. Biol."},{"key":"2022103110523701200_DMM049516C49","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.canlet.2020.07.025","article-title":"JNK signaling contributes to skeletal muscle wasting and protein turnover in pancreatic cancer cachexia","volume":"491","author":"Mulder","year":"2020","journal-title":"Cancer Lett."},{"key":"2022103110523701200_DMM049516C50","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1124\/jpet.119.259663","article-title":"Clinically Advanced p38 Inhibitors Suppress DUX4 Expression in Cellular and Animal Models of Facioscapulohumeral Muscular Dystrophy","volume":"370","author":"Oliva","year":"2019","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"2022103110523701200_DMM049516C51","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/nmeth.4197","article-title":"Salmon provides fast and bias-aware quantification of transcript expression","volume":"14","author":"Patro","year":"2017","journal-title":"Nat. Methods"},{"key":"2022103110523701200_DMM049516C52","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1084\/jem.20041502","article-title":"Essential role of p53 phosphorylation by p38 MAPK in apoptosis induction by the HIV-1 envelope","volume":"201","author":"Perfettini","year":"2005","journal-title":"J. Exp. Med."},{"key":"2022103110523701200_DMM049516C75","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1214\/16-AOAS920","article-title":"Robust hyperparameter estimation protects against hypervariable genes and improves power to detect differential expression","volume":"10","author":"Phipson","year":"2016","journal-title":"Ann. Appl. Stat."},{"key":"2022103110523701200_DMM049516C53","doi-asserted-by":"publisher","first-page":"5901","DOI":"10.1093\/hmg\/ddv315","article-title":"Endogenous DUX4 expression in FSHD myotubes is sufficient to cause cell death and disrupts RNA splicing and cell migration pathways","volume":"24","author":"Rickard","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"2022103110523701200_DMM049516C76","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"2022103110523701200_DMM049516C54","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1124\/jpet.119.264689","article-title":"p38\u03b1 regulates expression of DUX4 in a model of facioscapulohumeral muscular dystrophy","volume":"374","author":"Rojas","year":"2020","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"2022103110523701200_DMM049516C55","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/B978-0-12-396456-4.00013-4","article-title":"Role of the JNK pathway in human diseases","volume":"106","author":"Sabapathy","year":"2012","journal-title":"Prog. Mol. Biol. Transl."},{"key":"2022103110523701200_DMM049516C56","doi-asserted-by":"publisher","first-page":"3586","DOI":"10.1021\/pr400098r","article-title":"Measuring and managing ratio compression for accurate iTRAQ\/TMT quantification","volume":"12","author":"Savitski","year":"2013","journal-title":"J. Proteome Res."},{"key":"2022103110523701200_DMM049516C57","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1186\/s13023-021-01760-1","article-title":"Facioscapulohumeral muscular dystrophy: genetics, gene activation and downstream signalling with regard to recent therapeutic approaches: an update","volume":"16","author":"Sch\u00e4tzl","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"2022103110523701200_DMM049516C58","doi-asserted-by":"publisher","first-page":"e1006658","DOI":"10.1371\/journal.pgen.1006658","article-title":"DUX4-induced dsRNA and MYC mRNA stabilization activate apoptotic pathways in human cell models of facioscapulohumeral dystrophy","volume":"13","author":"Shadle","year":"2017","journal-title":"PLoS Genet."},{"key":"2022103110523701200_DMM049516C59","doi-asserted-by":"publisher","first-page":"e1001181","DOI":"10.1371\/journal.pgen.1001181","article-title":"Facioscapulohumeral dystrophy: incomplete suppression of a retrotransposed gene","volume":"6","author":"Snider","year":"2010","journal-title":"PLoS Genet."},{"key":"2022103110523701200_DMM049516C60","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.12688\/f1000research.7563.1","article-title":"Differential analyses for RNA-seq: transcript-level estimates improve gene-level inferences","volume":"4","author":"Soneson","year":"2015","journal-title":"F1000research"},{"key":"2022103110523701200_DMM049516C61","doi-asserted-by":"publisher","first-page":"4924","DOI":"10.1128\/MCB.18.8.4924","article-title":"Characterization of SRp46, a novel human SR splicing factor encoded by a PR264\/SC35 retropseudogene","volume":"18","author":"Soret","year":"1998","journal-title":"Mol. Cell. Biol."},{"key":"2022103110523701200_DMM049516C62","doi-asserted-by":"publisher","first-page":"1916","DOI":"10.1212\/CON.0000000000000399","article-title":"Facioscapulohumeral muscular dystrophy","volume":"22","author":"Statland","year":"2016","journal-title":"Continuum (Minneapolis, Minn.)"},{"key":"2022103110523701200_DMM049516C63","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2022103110523701200_DMM049516C64","first-page":"4177","article-title":"Human mitogen-activated protein kinase kinase 4 as a candidate tumor suppressor","volume":"57","author":"Teng","year":"1997","journal-title":"Cancer Res."},{"key":"2022103110523701200_DMM049516C65","doi-asserted-by":"publisher","first-page":"eaax8978","DOI":"10.1126\/sciadv.aax8978","article-title":"Beyond mass spectrometry, the next step in proteomics","volume":"6","author":"Timp","year":"2020","journal-title":"Sci. Adv."},{"key":"2022103110523701200_DMM049516C66","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1093\/embo-reports\/kve046","article-title":"ASK1 is required for sustained activations of JNK\/p38 MAP kinases and apoptosis","volume":"2","author":"Tobiume","year":"2001","journal-title":"EMBO Rep."},{"key":"2022103110523701200_DMM049516C67","doi-asserted-by":"publisher","first-page":"e11752","DOI":"10.7554\/eLife.11752","article-title":"A new view of transcriptome complexity and regulation through the lens of local splicing variations","volume":"5","author":"Vaquero-Garcia","year":"2016","journal-title":"eLife"},{"key":"2022103110523701200_DMM049516C68","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1002\/ana.22275","article-title":"DUX4, a candidate gene for facioscapulohumeral muscular dystrophy, causes p53-dependent myopathy in vivo","volume":"69","author":"Wallace","year":"2010","journal-title":"Ann. Neurol."},{"key":"2022103110523701200_DMM049516C69","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1038\/ng0992-26","article-title":"Chromosome 4q DNA rearrangements associated with facioscapulohumeral muscular dystrophy","volume":"2","author":"Wijmenga","year":"1992","journal-title":"Nat. Genet."},{"key":"2022103110523701200_DMM049516C70","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1080\/14756366.2020.1720013","article-title":"Selective inhibitors for JNK signalling: a potential targeted therapy in cancer","volume":"35","author":"Wu","year":"2020","journal-title":"J. Enzym. Inhib. Med. Ch."},{"key":"2022103110523701200_DMM049516C71","doi-asserted-by":"publisher","first-page":"e1003947","DOI":"10.1371\/journal.pgen.1003947","article-title":"DUX4 binding to retroelements creates promoters that are active in FSHD muscle and testis","volume":"9","author":"Young","year":"2013","journal-title":"PLoS Genet."},{"key":"2022103110523701200_DMM049516C72","doi-asserted-by":"publisher","first-page":"5193","DOI":"10.1074\/jbc.274.8.5193","article-title":"p38 mitogen-activated protein kinase pathway promotes skeletal muscle differentiation. Participation of the Mef2c transcription factor","volume":"274","author":"Zetser","year":"1999","journal-title":"J. Biol. Chem."}],"container-title":["Disease Models &amp; Mechanisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.049516\/2174332\/dmm049516.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.049516\/2212250\/dmm049516.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.049516\/2212250\/dmm049516.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T10:52:54Z","timestamp":1667213574000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dmm\/article\/15\/11\/dmm049516\/278787\/DUX4-expression-activates-JNK-and-p38-MAP-kinases"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,31]]},"references-count":77,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2022,11,1]]}},"URL":"https:\/\/doi.org\/10.1242\/dmm.049516","relation":{},"ISSN":["1754-8403","1754-8411"],"issn-type":[{"value":"1754-8403","type":"print"},{"value":"1754-8411","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,31]]},"article-number":"dmm049516"}}