Loss of PUMA (BBC3) does not prevent thrombocytopenia caused by the loss of BCL-XL (BCL2L1)
- Author(s)
- Delbridge, AR; Chappaz, S; Ritchie, ME; Kile, BT; Strasser, A; Grabow, S;
- Journal Title
- Br J Haematol
- Publication Type
- Journal Article in press
- 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.
- Publisher
- Wiley
- Research Division(s)
- Molecular Genetics Of Cancer; Chemical Biology; Molecular Medicine
- PubMed ID
- 27221652
- Publisher's Version
- https://doi.org/10.1111/bjh.14155
- NHMRC Grants
- NHMRC/575535, NHMRC/1016701, NHMRC/1016647, NHMRC/1020363, NHMRC/1063008, NHMRC/361646,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2016-06-16 10:27:04
Last Modified: 2016-06-16 11:23:53