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dc.contributor.authorSancho, Ana
dc.contributor.authorDuran, Jordi
dc.contributor.authorGarcia-Espana, Antonio
dc.contributor.authorMauvezin, Caroline
dc.contributor.authorAlemu, Endalkachew Ashenafi
dc.contributor.authorLamark, Trond
dc.contributor.authorMacias, Maria J.
dc.contributor.authorDeSalle, Rob
dc.contributor.authorRoyo, Miriam
dc.contributor.authorSala, David
dc.contributor.authorChicote, Javier U.
dc.contributor.authorPalacin, Manuel
dc.contributor.authorJohansen, Terje
dc.contributor.authorZorzano, Antonio
dc.date.accessioned2013-03-13T14:49:24Z
dc.date.available2013-03-13T14:49:24Z
dc.date.issued2012
dc.description.abstractHuman DOR/TP53INP2 displays a unique bifunctional role as a modulator of autophagy and gene transcription. However, the domains or regions of DOR that participate in those functions have not been identified. Here we have performed structure/function analyses of DOR guided by identification of conserved regions in the DOR gene family by phylogenetic reconstructions. We show that DOR is present in metazoan species. Invertebrates harbor only one gene, DOR/Tp53inp2, and in the common ancestor of vertebrates Tp53inp1 may have arisen by gene duplication. In keeping with these data, we show that human TP53INP1 regulates autophagy and that different DOR/TP53INP2 and TP53INP1 proteins display transcriptional activity. The use of molecular evolutionary information has been instrumental to determine the regions that participate in DOR functions. DOR and TP53INP1 proteins share two highly conserved regions (region 1, aa residues 28–42; region 2, 66–112 in human DOR). Mutation of conserved hydrophobic residues in region 1 of DOR (that are part of a nuclear export signal, NES) reduces transcriptional activity, and blocks nuclear exit and autophagic activity under autophagy-activated conditions. We also identify a functional and conserved LC3-interacting motif (LIR) in region 1 of DOR and TP53INP1 proteins. Mutation of conserved acidic residues in region 2 of DOR reduces transcriptional activity, impairs nuclear exit in response to autophagy activation, and disrupts autophagy. Taken together, our data reveal DOR and TP53INP1 as dual regulators of transcription and autophagy, and identify two conserved regions in the DOR family that concentrate multiple functions crucial for autophagy and transcription.en
dc.identifier.citationPLoS ONE (2012), vol.7(3): e34034en
dc.identifier.cristinIDFRIDAID 946478
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0034034
dc.identifier.issn1932-6203
dc.identifier.urihttps://hdl.handle.net/10037/5010
dc.identifier.urnURN:NBN:no-uit_munin_4712
dc.language.isoengen
dc.publisherPublic Library of Science (PLoS)en
dc.rights.accessRightsopenAccess
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical genetics: 714en
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk genetikk: 714en
dc.titleDOR/Tp53inp2 and Tp53inp1 Constitute a Metazoan Gene Family Encoding Dual Regulators of Autophagy and Transcriptionen
dc.typeJournal articleen
dc.typeTidsskriftartikkelen
dc.typePeer revieweden


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