Journal article
Loss of PUMA (BBC3) does not prevent thrombocytopenia caused by the loss of BCL-XL (BCL2L1)
ARD Delbridge, S Chappaz, ME Ritchie, BT Kile, A Strasser, S Grabow
British Journal of Haematology | WILEY | Published : 2016
DOI: 10.1111/bjh.14155
Abstract
Apoptosis is required to maintain tissue homeostasis in multicellular organisms. Platelets, the anucleate cells that are essential for blood clotting, are a prime example. Their brief life span in the circulation is regulated by the intrinsic apoptosis pathway. Pro-survival BCL-XL (also termed BCL2L1) is essential for platelet viability. It functions to restrain the pro-apoptotic BCL-2 family members BAK (also termed BAK1) and BAX, the essential mediators of intrinsic apoptosis. Genetic deletion or pharmacological inhibition of BCL-XL results in thrombocytopenia. Conversely, deletion of BAK in platelets doubles their circulating life span. However, what triggers platelet apoptosis in vivo re..
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Awarded by Leukemia and Lymphoma Society
Funding Acknowledgements
We thank Drs P. Bouillet, J. M. Adams, L. Hennighausen and A. Villunger for mice; E. Major, S. Ross, T. Carle, T. Gibbs, S. Green, C. Gall, S. O'Connor, J. Mansheim, K. McKenzie and G. Siciliano for outstanding animal husbandry; B. Helbert for genotyping; J. Corbin and J. McManus for automated blood analysis. This work was supported by a Project Grant (575535), Program Grants (1016701, 1016647), Fellowships (AS Australia Fellowship 1020363, BTK 1063008) and an Independent Research Institutes Infrastructure Support Scheme Grant (361646) from the Australian National Health and Medical Research Council; a fellowship from the Sylvia and Charles Viertel Foundation (BTK); the Australian Cancer Research Fund; the Cancer Council of Victoria (SG, ARDD); Leukaemia Foundation Australia (SG); the Lady Tata Memorial Trust (SG); Cure Brain Cancer Australia (AS); the Leukemia and Lymphoma Society (AS, SOCR Grant #7001-03), Melbourne International Research and the Melbourne International Fee Remission Scholarship (University of Melbourne, SG) and Cancer Therapeutics CRC Top up Scholarship (SG, ARDD). The estate of Anthony (Toni) Redstone OAM, University of Melbourne International Research and International Fee Remission Scholarships (SG), Australian Postgraduate Award (ARDD), and the operational infrastructure grants through the Australian Government TRESS and the Victorian State Government OIS.