Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/108544
Title: The transcriptional repressor HDAC7 promotes apoptosis and c-Myc downregulation in particular types of leukemia and lymphoma
Author: Barneda-Zahonero, Bruna
Collazo, Olga
Azagra, Alba
Fernández-Duran, Irene
Serra-Musach, Jordi
Islam, Abul B.M.M.K.
Vega-García, N.
Malatesta, R.
Camós, M.
Gómez, Antonio
Román González, Lidia
Vidal-Bel, August
López Bigas, Núria
Villanueva Garatachea, Alberto
Esteller, Manel
Parra Bola, Mª Isabel
Keywords: Histones
Leucèmia
Limfomes
Apoptosi
Cèl·lules B
Histones
Leukemia
Lymphomas
Apoptosis
B cells
Issue Date: 12-Feb-2015
Publisher: Nature Publishing Group
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.
Note: Reproducció del document publicat a: https://doi.org/10.1038/cddis.2014.594
It is part of: Cell Death and Disease, 2015, vol. 6, p. e1635
Related resource: https://doi.org/10.1038/cddis.2014.594
URI: http://hdl.handle.net/2445/108544
ISSN: 2041-4889
Appears in Collections:Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Ciències Fisiològiques)

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