title: LOXL2 Oxidizes Methylated TAF10 and Controls TFIID-Dependent Genes during Neural Progenitor Differentiation.
abstract: Protein function is often regulated and controlled by posttranslational modifications, such as oxidation. Although oxidation has been mainly considered to be uncontrolled and nonenzymatic, many enzymatic oxidations occur on enzyme-selected lysine residues; for instance, LOXL2 oxidizes lysines by converting the ε-amino groups into aldehyde groups. Using an unbiased proteomic approach, we have identified methylated TAF10, a member of the TFIID complex, as a LOXL2 substrate. LOXL2 oxidation of TAF10 induces its release from its promoters, leading to a block in TFIID-dependent gene transcription. In embryonic stem cells, this results in the inactivation of the pluripotency genes and loss of the pluripotent capacity. During zebrafish development, the absence of LOXL2 resulted in the aberrant overexpression of the neural progenitor gene Sox2 and impaired neural differentiation. Thus, lysine oxidation of the transcription factor TAF10 is a controlled protein modification and demonstrates a role for protein oxidation in regulating pluripotency genes.
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain.
authors.forename: Ane
authors.initials: A
authors.lastname: Iturbide
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Pascual-Reguant
authors.affiliation: Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Fargas
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain.
authors.forename: Joan Pau
authors.initials: JP
authors.lastname: Cebrià
authors.affiliation: Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, Spain.
authors.forename: Berta
authors.initials: B
authors.lastname: Alsina
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain; Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: García de Herreros
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), 08003 Barcelona, Spain. Electronic address: speiro@imim.es.
authors.forename: Sandra
authors.initials: S
authors.lastname: Peiró
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation; D044127:Epigenesis, Genetic; D057809:HEK293 Cells; D006801:Humans; D008745:Methylation; D058953:Neural Stem Cells / Q000502:physiology*; D010084:Oxidation-Reduction; D011499:Protein Processing, Post-Translational; D035381:TATA-Binding Protein Associated Factors / Q000378:metabolism*; D035362:Transcription Factor TFIID / Q000378:metabolism / Q000502:physiology*; D015027:Zebrafish
chemical_list: C089768:TAF10 protein, human; D035381:TATA-Binding Protein Associated Factors; D035362:Transcription Factor TFIID; D000594:Amino Acid Oxidoreductases; C119091:LOXL2 protein, human