The transcriptional repressor HDAC7 promotes apoptosis and c-Myc downregulation in particular types of leukemia and lymphoma

Mostra el registre complet Registre parcial de l'ítem

• dc.contributor.author Barneda Zahonero, Brunaca
• dc.contributor.author Collazo, Olgaca
• dc.contributor.author Azagra Malo, Albertca
• dc.contributor.author Fernández Duran, Ireneca
• dc.contributor.author Serra Musach, Jordica
• dc.contributor.author Islam, Abul, 1978-ca
• dc.contributor.author Vega García, Nereaca
• dc.contributor.author Malatesta, Robertaca
• dc.contributor.author Camós, Mireiaca
• dc.contributor.author Gómez, Antonioca
• dc.contributor.author Román González, Lidiaca
• dc.contributor.author Vidal, Augustca
• dc.contributor.author López Bigas, Núriaca
• dc.contributor.author Villanueva, Albertoca
• dc.contributor.author Esteller, Manelca
• dc.contributor.author Parra, Maribelca
• dc.date.accessioned 2016-02-10T15:38:52Z
• dc.date.available 2016-02-10T15:38:52Z
• dc.date.issued 2015
• dc.description.abstract The generation of B cells is a complex process requiring several cellular transitions, including cell commitment and differentiation. Proper transcriptional control to establish the genetic programs characteristic of each cellular stage is essential for the correct development of B lymphocytes. Deregulation of these particular transcriptional programs may result in a block in B-cell maturation, contributing to the development of hematological malignancies such as leukemia and lymphoma. However, very little is currently known about the role of transcriptional repressors in normal and aberrant B lymphopoiesis. Here we report that histone deacetylase 7 (HDAC7) is underexpressed in pro-B acute lymphoblastic leukemia (pro-B-ALL) and Burkitt lymphoma. Ectopic expression of HDAC7 induces apoptosis, leads to the downregulation of c-Myc and inhibits the oncogenic potential of cells in vivo, in a xenograft model. Most significantly, we have observed low levels of HDAC7 expression in B-ALL patient samples, which is correlated with the increased levels of c-Myc. From a mechanistic angle, we show that ectopically expressed HDAC7 localizes to the nucleus and interacts with the transcription factor myocyte enhancer factor C (MEF2C) and the corepressors HDAC3 and SMRT. Accordingly, both the HDAC7-MEF2C interaction domain as well as its catalytic domain are involved in the reduced cell viability induced by HDAC7. We conclude that HDAC7 has a potent anti-oncogenic effect on specific B-cell malignancies, indicating that its deregulation may contribute to the pathogenesis of the disease.ca
• dc.description.sponsorship This work was supported by a grant from the Spanish Ministry of Economy and Competitiveness (MINECO; SAF2011-28290; to MP). MP was supported by a Ramón y Cajal contract from the Spanish Ministry of Science and Innovation (MICIIN). LR-G was supported by an IDIBELL PhD fellowship. NL-B acknowledges the funding from MICIIN (SAF2012-36199).
• dc.format.mimetype application/pdfca
• dc.identifier.citation Barneda-Zahonero B, Collazo O, Azagra A, Fernández-Duran I, Serra-Musach J A et al. The transcriptional repressor HDAC7 promotes apoptosis and c-Myc downregulation in particular types of leukemia and lymphoma. Cell death & disease. 2015; 6: e1635. DOI 10.1038/cddis.2014.594ca
• dc.identifier.doi http://dx.doi.org/10.1038/cddis.2014.594
• dc.identifier.issn 2041-4889
• dc.identifier.uri http://hdl.handle.net/10230/25773
• dc.language.iso engca
• dc.publisher Nature Publishing Groupca
• dc.relation.ispartof Cell death & disease. 2015; 6: e1635
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2012-36199
• dc.rights © Nature Publishing Group. http://www.nature.com/cddis/journal/v6/n2/full/cddis2014594a.html/nCell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International Licenceca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/ca
• dc.subject.other Apoptosica
• dc.subject.other Leucèmiaca
• dc.title The transcriptional repressor HDAC7 promotes apoptosis and c-Myc downregulation in particular types of leukemia and lymphomaca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersionca