Loss of PUMA (BBC3) does not prevent thrombocytopenia caused by the loss of BCL-XL (BCL2L1)

Alex R. D. Delbridge, Stephane Chappaz, Matthew E. Ritchie, Benjamin T. Kile, Andreas Strasser, Stephanie Grabow

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)962-969
Number of pages8
JournalBritish Journal of Haematology
Volume174
Issue number6
DOIs
Publication statusPublished - Sep 2016
Externally publishedYes

Keywords

  • apoptosis
  • cell biology
  • platelets
  • therapy
  • thrombocytopenia

Cite this

Delbridge, Alex R. D. ; Chappaz, Stephane ; Ritchie, Matthew E. ; Kile, Benjamin T. ; Strasser, Andreas ; Grabow, Stephanie. / Loss of PUMA (BBC3) does not prevent thrombocytopenia caused by the loss of BCL-XL (BCL2L1). In: British Journal of Haematology. 2016 ; Vol. 174, No. 6. pp. 962-969.
@article{a36da8ddacc5407491c3e67602f7d503,
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.",
keywords = "apoptosis, cell biology, platelets, therapy, thrombocytopenia",
author = "Delbridge, {Alex R. D.} and Stephane Chappaz and Ritchie, {Matthew E.} and Kile, {Benjamin T.} and Andreas Strasser and Stephanie Grabow",
year = "2016",
month = "9",
doi = "10.1111/bjh.14155",
language = "English",
volume = "174",
pages = "962--969",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "John Wiley & Sons",
number = "6",

}

Loss of PUMA (BBC3) does not prevent thrombocytopenia caused by the loss of BCL-XL (BCL2L1). / Delbridge, Alex R. D.; Chappaz, Stephane; Ritchie, Matthew E.; Kile, Benjamin T.; Strasser, Andreas; Grabow, Stephanie.

In: British Journal of Haematology, Vol. 174, No. 6, 09.2016, p. 962-969.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Loss of PUMA (BBC3) does not prevent thrombocytopenia caused by the loss of BCL-XL (BCL2L1)

AU - Delbridge, Alex R. D.

AU - Chappaz, Stephane

AU - Ritchie, Matthew E.

AU - Kile, Benjamin T.

AU - Strasser, Andreas

AU - Grabow, Stephanie

PY - 2016/9

Y1 - 2016/9

N2 - 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.

AB - 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.

KW - apoptosis

KW - cell biology

KW - platelets

KW - therapy

KW - thrombocytopenia

UR - http://www.scopus.com/inward/record.url?scp=84985905824&partnerID=8YFLogxK

U2 - 10.1111/bjh.14155

DO - 10.1111/bjh.14155

M3 - Article

VL - 174

SP - 962

EP - 969

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 6

ER -