title: Loss of PUMA (BBC3) does not prevent thrombocytopenia caused by the loss of BCL-XL (BCL2L1).
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 remains unclear. The pro-apoptotic BH3-only proteins are essential for initiating apoptosis in nucleated cells, and there is some evidence to suggest they also play a role in platelet biology. We investigated whether PUMA (also termed BBC3), a potent BH3-only protein that can inhibit all pro-survival BCL-2 family members as well as directly activate BAX, regulates the death of platelets. Surprisingly, loss of PUMA had no impact on the loss of platelets caused by loss of BCL-XL. It therefore remains to be established whether other BH3-only proteins play a critical role in induction of apoptosis in platelets or whether their death is controlled solely by the interactions between BCL-XL with BAK and BAX.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne, Vic., Australia.|Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.
authors.forename: Alex R D
authors.initials: AR
authors.lastname: Delbridge
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne, Vic., Australia.|Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.
authors.forename: Stephane
authors.initials: S
authors.lastname: Chappaz
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne, Vic., Australia.|Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Ritchie
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne, Vic., Australia.|Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.
authors.forename: Benjamin T
authors.identifier: 0000-0002-8836-8947
authors.initials: BT
authors.lastname: Kile
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne, Vic., Australia.|Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Strasser
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne, Vic., Australia.|Department of Medical Biology, University of Melbourne, Melbourne, Vic., Australia.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Grabow
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000172:deficiency* / Q000235:genetics; D001792:Blood Platelets / Q000378:metabolism; D004195:Disease Models, Animal; D017353:Gene Deletion; D015870:Gene Expression; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics; D013921:Thrombocytopenia / Q000097:blood / Q000235:genetics*; D051028:bcl-2-Associated X Protein / Q000172:deficiency* / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D011518:Proto-Oncogene Proteins; D051028:bcl-2-Associated X Protein
keywords: apoptosis; cell biology; platelets; therapy; thrombocytopenia