Journal article
Triggering of Apoptosis by Puma Is Determined by the Threshold Set by Prosurvival Bcl-2 Family Proteins
BA Callus, DM Moujallad, J Silke, R Gerl, AM Jabbour, PG Ekert, DL Vaux
Journal of Molecular Biology | ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD | Published : 2008
Abstract
Puma (p53 upregulated modulator of apoptosis) belongs to the BH3 (Bcl-2 homology 3)-only protein family of apoptotic regulators. Its expression is induced by various apoptotic stimuli, including irradiation and cytokine withdrawal. Using an inducible system to express Puma, we investigated the nature of Puma-induced apoptosis. In BaF3 cells, expression of Puma caused rapid caspase-mediated cleavage of ICAD (inhibitor of caspase-activated deoxyribonuclease) and Mcl-1 (myeloid cell leukemia 1), leading to complete loss of cell viability. Surprisingly, Puma protein levels peaked within 2 h of its induction and subsequently declined to basal levels. Maximal Puma abundance coincided with the onse..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
This work was supported by funds from the National Health and Medical Research Council (program grant 461221 and project grant 436936) and a Leukemia and Lymphoma Society Center grant. We thank David Huang (WEHI) for generously providing human Puma cDNA, WT and bax/bak DKO MEFs, and anti-ICAD as well as Lorraine O'Reilly for providing the anti-Bcl-2 antibody. BaF<INF>3</INF> cells were obtained from Doug Hilton (WEHI). We thank various members of D. L. Vaux's laboratory for helpful discussions. D. L. Vaux is a National Health and Medical Research Council Australia Fellow. P.G. Ekert is a Senior Medical Research Fellow of the Sylvia and Charles Viertel Charitable Foundation.