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Megakaryocytes possess a functional intrinsic apoptosis pathway that must be restrained to survive and produce platelets.

Josefsson EC, James C, Henley KJ, Debrincat MA, Rogers KL, Dowling MR, White MJ, Kruse EA, Lane RM, Ellis S, Nurden P, Mason KD, O'Reilly LA, Roberts AW, Metcalf D, Huang DC, Kile BT.

J Exp Med. 2011 Sep 26;208(10):2017-31. doi: 10.1084/jem.20110750. Epub 2011 Sep 12.


Caspase-9 mediates the apoptotic death of megakaryocytes and platelets, but is dispensable for their generation and function.

White MJ, Schoenwaelder SM, Josefsson EC, Jarman KE, Henley KJ, James C, Debrincat MA, Jackson SP, Huang DC, Kile BT.

Blood. 2012 May 3;119(18):4283-90. doi: 10.1182/blood-2011-11-394858. Epub 2012 Jan 31.


BH3-only activator proteins Bid and Bim are dispensable for Bak/Bax-dependent thrombocyte apoptosis induced by Bcl-xL deficiency: molecular requisites for the mitochondrial pathway to apoptosis in platelets.

Kodama T, Takehara T, Hikita H, Shimizu S, Shigekawa M, Li W, Miyagi T, Hosui A, Tatsumi T, Ishida H, Kanto T, Hiramatsu N, Yin XM, Hayashi N.

J Biol Chem. 2011 Apr 22;286(16):13905-13. doi: 10.1074/jbc.M110.195370. Epub 2011 Mar 2.


Actin inhibition increases megakaryocyte proplatelet formation through an apoptosis-dependent mechanism.

Avanzi MP, Izak M, Oluwadara OE, Mitchell WB.

PLoS One. 2015 Apr 14;10(4):e0125057. doi: 10.1371/journal.pone.0125057. eCollection 2015.


Regulation of stress-induced nuclear protein redistribution: a new function of Bax and Bak uncoupled from Bcl-x(L).

Lindenboim L, Blacher E, Borner C, Stein R.

Cell Death Differ. 2010 Feb;17(2):346-59. doi: 10.1038/cdd.2009.145. Epub 2009 Oct 9.


Mcl-1 and Bcl-x(L) coordinately regulate megakaryocyte survival.

Debrincat MA, Josefsson EC, James C, Henley KJ, Ellis S, Lebois M, Betterman KL, Lane RM, Rogers KL, White MJ, Roberts AW, Harvey NL, Metcalf D, Kile BT.

Blood. 2012 Jun 14;119(24):5850-8. doi: 10.1182/blood-2011-12-398834. Epub 2012 Feb 28.


Caspase-mediated Bak activation and cytochrome c release during intrinsic apoptotic cell death in Jurkat cells.

Shawgo ME, Shelton SN, Robertson JD.

J Biol Chem. 2008 Dec 19;283(51):35532-8. doi: 10.1074/jbc.M807656200. Epub 2008 Oct 15.


Platelet production proceeds independently of the intrinsic and extrinsic apoptosis pathways.

Josefsson EC, Burnett DL, Lebois M, Debrincat MA, White MJ, Henley KJ, Lane RM, Moujalled D, Preston SP, O'Reilly LA, Pellegrini M, Metcalf D, Strasser A, Kile BT.

Nat Commun. 2014 Mar 17;5:3455. doi: 10.1038/ncomms4455.


P2Y12 protects platelets from apoptosis via PI3k-dependent Bak/Bax inactivation.

Zhang S, Ye J, Zhang Y, Xu X, Liu J, Zhang SH, Kunapuli SP, Ding Z.

J Thromb Haemost. 2013 Jan;11(1):149-60. doi: 10.1111/jth.12063.


Delayed-onset caspase-dependent massive hepatocyte apoptosis upon Fas activation in Bak/Bax-deficient mice.

Hikita H, Takehara T, Kodama T, Shimizu S, Shigekawa M, Hosui A, Miyagi T, Tatsumi T, Ishida H, Li W, Kanto T, Hiramatsu N, Shimizu S, Tsujimoto Y, Hayashi N.

Hepatology. 2011 Jul;54(1):240-51. doi: 10.1002/hep.24305. Epub 2011 Apr 11.


p14(ARF)-induced apoptosis in p53 protein-deficient cells is mediated by BH3-only protein-independent derepression of Bak protein through down-regulation of Mcl-1 and Bcl-xL proteins.

Müer A, Overkamp T, Gillissen B, Richter A, Pretzsch T, Milojkovic A, Dörken B, Daniel PT, Hemmati P.

J Biol Chem. 2012 May 18;287(21):17343-52. doi: 10.1074/jbc.M111.314898. Epub 2012 Feb 21.


The multidomain proapoptotic molecules Bax and Bak are directly activated by heat.

Pagliari LJ, Kuwana T, Bonzon C, Newmeyer DD, Tu S, Beere HM, Green DR.

Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):17975-80. Epub 2005 Dec 5.


Programmed anuclear cell death delimits platelet life span.

Mason KD, Carpinelli MR, Fletcher JI, Collinge JE, Hilton AA, Ellis S, Kelly PN, Ekert PG, Metcalf D, Roberts AW, Huang DC, Kile BT.

Cell. 2007 Mar 23;128(6):1173-86.


Key role for Bak activation and Bak-Bax interaction in the apoptotic response to vinblastine.

Upreti M, Chu R, Galitovskaya E, Smart SK, Chambers TC.

Mol Cancer Ther. 2008 Jul;7(7):2224-32. doi: 10.1158/1535-7163.MCT-07-2299.


The role of apoptosis in megakaryocytes and platelets.

Kile BT.

Br J Haematol. 2014 Apr;165(2):217-26. doi: 10.1111/bjh.12757. Epub 2014 Jan 28. Review.


Bnip3 mediates mitochondrial dysfunction and cell death through Bax and Bak.

Kubli DA, Ycaza JE, Gustafsson AB.

Biochem J. 2007 Aug 1;405(3):407-15.


Indirect effects of Bax and Bak initiate the mitochondrial alterations that lead to cytochrome c release during arsenic trioxide-induced apoptosis.

Nutt LK, Gogvadze V, Uthaisang W, Mirnikjoo B, McConkey DJ, Orrenius S.

Cancer Biol Ther. 2005 Apr;4(4):459-67. Epub 2005 Apr 28.


Pro-apoptotic Bax is the major and Bak an auxiliary effector in cytokine deprivation-induced mast cell apoptosis.

Karlberg M, Ekoff M, Labi V, Strasser A, Huang D, Nilsson G.

Cell Death Dis. 2010 May 13;1:e43. doi: 10.1038/cddis.2010.20.


Vesicular stomatitis virus induces apoptosis primarily through Bak rather than Bax by inactivating Mcl-1 and Bcl-XL.

Pearce AF, Lyles DS.

J Virol. 2009 Sep;83(18):9102-12. doi: 10.1128/JVI.00436-09. Epub 2009 Jul 8.

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