Journal article
Hoxb8 regulates expression of microRNAs to control cell death and differentiation
M Salmanidis, G Brumatti, N Narayan, BD Green, JA Van Den Bergen, JJ Sandow, AG Bert, N Silke, R Sladic, H Puthalakath, L Rohrbeck, T Okamoto, P Bouillet, MJ Herold, GJ Goodall, AM Jabbour, PG Ekert
Cell Death and Differentiation | Published : 2013
DOI: 10.1038/cdd.2013.92
Abstract
Hoxb8 overexpression immortalises haematopoietic progenitor cells in a growth-factor-dependant manner and co-operates with interleukin-3 (IL-3) to cause acute myeloid leukaemia. To further understand how Hoxb8 contributes to myeloid cell immortalisation, we generated IL-3-dependant myeloid cells expressing Hoxb8 under the control of an inducible promoter. Downregulation of Hoxb8, in the presence of IL-3, caused cell-cycle arrest and apoptosis in the majority of cells. Apoptosis was dependant on Bax and Bak and, in part, on Bim, which was repressed by Hoxb8. Deletion of the miR-17∼92 seed sequences in the Bim 3′UTR abolished Hoxb8-dependant regulation of Bim reporter constructs. Expression of..
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Funding Acknowledgements
We thank Dr. J Silke for the provision of lentiviral vectors and valuable advise, Dr. Lorraine O'Reilly, Professor Andreas Strasser and Dr. David Huang for antibodies and Bax<SUP>-/-</SUP>; Bak<SUP>-/-</SUP> mice. Dr. Matt Burton for assistance with flow cytometry. This work was supported by the National Health and Medical Research Council of Australia. PGE is supported by the Sylvia and Charles Viertel Senior Medical Fellowship. MS is supported by the National Health and Medical Research Council (NHMRC) postgraduate scholarship. This work was supported by operational infrastructure grants through the Australian Government IRISS and the Victorian State Government OIS.