title: Ankrd2 is a modulator of NF-κB-mediated inflammatory responses during muscle differentiation.
abstract: Adaptive responses of skeletal muscle regulate the nuclear shuttling of the sarcomeric protein Ankrd2 that can transduce different stimuli into specific adaptations by interacting with both structural and regulatory proteins. In a genome-wide expression study on Ankrd2-knockout or -overexpressing primary proliferating or differentiating myoblasts, we found an inverse correlation between Ankrd2 levels and the expression of proinflammatory genes and identified Ankrd2 as a potent repressor of inflammatory responses through direct interaction with the NF-κB repressor subunit p50. In particular, we identified Gsk3β as a novel direct target of the p50/Ankrd2 repressosome dimer and found that the recruitment of p50 by Ankrd2 is dependent on Akt2-mediated phosphorylation of Ankrd2 upon oxidative stress during myogenic differentiation. Surprisingly, the absence of Ankrd2 in slow muscle negatively affected the expression of cytokines and key calcineurin-dependent genes associated with the slow-twitch muscle program. Thus, our findings support a model in which alterations in Ankrd2 protein and phosphorylation levels modulate the balance between physiological and pathological inflammatory responses in muscle.
authors.affiliation: Department of Biology, Innovative Biotechnologies Interdepartmental Research Center, University of Padova, Padova, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Bean
authors.affiliation: Department of Biology, Innovative Biotechnologies Interdepartmental Research Center, University of Padova, Padova, Italy.
authors.forename: N K
authors.initials: NK
authors.lastname: Verma
authors.affiliation: Institute of Biomedical Technologies, National Research Council, Milan, Italy.
authors.forename: D L
authors.initials: DL
authors.lastname: Yamamoto
authors.affiliation: Department of Biology, Innovative Biotechnologies Interdepartmental Research Center, University of Padova, Padova, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Chemello
authors.affiliation: Institute of Molecular Genetics, National Research Council, Bologna Unit/IOR, Bologna, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Cenni
authors.affiliation: 1] Department of Translational Medicine, University of Milan, Milan, Italy [2] Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: M C
authors.initials: MC
authors.lastname: Filomena
authors.affiliation: University of California, San Diego School of Medicine, La Jolla, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.affiliation: 1] Humanitas Clinical and Research Center, Rozzano, Milan, Italy [2] Milan Unit, Institute of Genetic and Biomedical Research, National Research Council, Milan, Italy.
authors.forename: M L
authors.identifier: 0000000188595034
authors.initials: ML
authors.lastname: Bang
authors.affiliation: Department of Biology, Innovative Biotechnologies Interdepartmental Research Center, University of Padova, Padova, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Lanfranchi
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000276:immunology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032342:Muscle Cells / Q000166:cytology* / Q000276:immunology; D009124:Muscle Proteins / Q000235:genetics / Q000276:immunology*; D018482:Muscle, Skeletal / Q000166:cytology* / Q000276:immunology; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology*; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology*; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: C432364:ANKRD2 protein, human; C485877:Ankrd2 protein, mouse; D009124:Muscle Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D012097:Repressor Proteins; D038362:Glycogen Synthase Kinase 3