Journal article

Myeloid progenitor cells lacking p53 exhibit delayed up-regulation of Puma and prolonged survival after cytokine deprivation

Anissa M Jabbour, Carmel P Daunt, Benjamin D Green, Sandra Vogel, Lavinia Gordon, Rachel S Lee, Natasha Silke, Richard B Pearson, Cassandra J Vandenberg, Priscilla N Kelly, Stephen L Nutt, Andreas Strasser, Christoph Borner, Paul G Ekert

Blood | AMER SOC HEMATOLOGY | Published : 2010

Abstract

Loss of p53-dependent apoptosis contributes to the development of hematologic malignancies and failure to respond to treatment. Proapoptotic Bcl-2 family member Puma is essential for apoptosis in HoxB8-immortalized interleukin-3 (IL-3)-dependent myeloid cell lines (FDM cells) provoked by IL-3 deprivation. p53 and FoxO3a can transcriptionally regulate Puma. To investigate which transcriptional regulator is responsible for IL-3 deprivation-induced Puma expression and apoptosis, we generated wild-type (WT), p53(-/-), and FoxO3a(-/-) FDM cells and found that p53(-/-) but not FoxO3a(-/-) cells were protected against IL-3 withdrawal. Loss of p21(cip/waf), which is critical for p53-mediated cell-cy..

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Grants

Awarded by National Health and Research Council (NHMRC)


Awarded by Deutsche Forschungsgemeinschaft (DFG)


Awarded by Jose Carreras Leukemia Foundation of Germany (DJCS)


Funding Acknowledgements

This work was supported by the National Health and Research Council (NHMRC; project grants 384404 and 43693; program grant 257502, A. S.; CDA461274, C. J. V.); the Deutsche Forschungsgemeinschaft (DFG; BO-1933, C. B., S. V.); the Excellence Initiative of the German Federal and State Governments (Spemann Graduate School of Biology and Medicine [SGBM], GSC-4, Centre for Biological Signaling Studies, bioss, EZC 294, C. B., S. V.); the Jose Carreras Leukemia Foundation of Germany (DJCS; R 06/09, C. B.); and by The Melbourne University Early Career Researcher Grant (A. M. J.). S. L. N. is supported by the Pfizer Australia Research Fellowship, and P. G. E. is supported by the Sylvia and Charles Viertel Senior Medical Fellowship.