Journal article
Mcl-1 and Bcl-xL coordinately regulate megakaryocyte survival
MA Debrincat, EC Josefsson, C James, KJ Henley, S Ellis, M Lebois, KL Betterman, RM Lane, KL Rogers, MJ White, AW Roberts, NL Harvey, D Metcalf, BT Kile
Blood | Published : 2012
Abstract
Mature megakaryocytes depend on the function of Bcl-xL, a member of the Bcl-2 family of prosurvival proteins, to proceed safely through the process of platelet shedding. Despite this, loss of Bcl-xL does not prevent the growth and maturation of megakaryocytes, suggesting redundancy with other prosurvival proteins. We therefore generated mice with a megakaryocyte-specific deletion of Mcl-1, which is known to be expressed in megakaryocytes. Megakaryopoiesis, platelet production, and platelet lifespan were unperturbed in Mcl-1Pf4Δ/Pf4Δ animals. However, treatment with ABT-737, a BH3 mimetic compound that inhibits the prosurvival proteins Bcl-2, Bcl-xL, and Bcl-w resulted in the complete ablatio..
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Awarded by Australian National Health and Medical Research Council (NHMRC)
Funding Acknowledgements
This work was supported by a Project grant (575535), a Program grant (461219), and an Independent Research Institutes Infrastructure Support Scheme grant (361646) from the Australian National Health and Medical Research Council (NHMRC); Fellowships from the Sylvia and Charles Viertel Foundation (B. T. K.), the Leukemia & Lymphoma Society (E.C.J.), NHMRC/Inserm (C.J.), EMBO (C.J.), NHMRC (A. W. R., B. T. K.); the Cancer Council of Victoria (D. M.) and the National Heart Foundation (N.L.H.); the Australian Cancer Research Fund, and a Victorian State Government Operational Infrastructure Support grant.