Bcl-2 family member Bfl-1/A1 sequesters truncated bid to inhibit is collaboration with pro-apoptotic Bak or Bax

The Journal of Biological Chemistry
Arlette B WernerJannie Borst

Abstract

Following caspase-8 mediated cleavage, a carboxyl-terminal fragment of the BH3 domain-only Bcl-2 family member Bid transmits the apoptotic signal from death receptors to mitochondria. In a screen for possible regulators of Bid, we defined Bfl-1/A1 as a potent Bid interacting protein. Bfl-1 is an anti-apoptotic Bcl-2 family member, whose preferential expression in hematopoietic cells and endothelium is controlled by inflammatory stimuli. Its mechanism of action is unknown. We find that Bfl-1 associates with both full-length Bid and truncated (t)Bid, via the Bid BH3 domain. Cellular expression of Bfl-1 confers protection against CD95- and Trail receptor-induced cytochrome c release. In vitro assays, using purified mitochondria and recombinant proteins, demonstrate that Bfl-1 binds full-length Bid, but does not interfere with its processing by caspase-8, or with its mitochondrial association. Confocal microscopy supports that Bfl-1, which at least in part constitutively localizes to mitochondria, does not impede tBid translocation. However, Bfl-1 remains tightly and selectively bound to tBid and blocks collaboration between tBid and Bax or Bak in the plane of the mitochondrial membrane, thereby preventing mitochondrial apoptotic a...Continue Reading

References

Feb 8, 1996·Nature·E H ChengJ M Hardwick
Aug 1, 1996·Human Gene Therapy·T M Kinsella, G P Nolan
Nov 15, 1996·Genes & Development·K WangS J Korsmeyer
May 2, 1998·The EMBO Journal·C ScaffidiM E Peter
Aug 15, 1998·Trends in Cell Biology·A Kelekar, C B Thompson
Dec 8, 1998·The Journal of Experimental Medicine·A HamasakiS Hatakeyama
Aug 4, 1999·Proceedings of the National Academy of Sciences of the United States of America·H H LeeG Cheng
Mar 25, 2000·Molecular and Cellular Biology·C ChenC Gélinas
Jun 13, 2000·The Journal of Biological Chemistry·P J DuriezA Karsan
Aug 10, 2000·Trends in Cell Biology·S Desagher, J C Martinou
Jan 14, 2001·The Journal of Biological Chemistry·B AntonssonJ C Martinou
Feb 13, 2001·Trends in Biochemical Sciences·J M Adams, S Cory
Mar 30, 2001·The Journal of Biological Chemistry·V MikhailovP Saikumar
Jul 21, 2001·Molecular Cell·J YuB Vogelstein
Jul 21, 2001·Molecular Cell·K Nakano, K H Vousden
Jul 21, 2001·Molecular and Cellular Biology·O MicheauJ Tschopp

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Citations

Apr 26, 2011·Apoptosis : an International Journal on Programmed Cell Death·Felix M WensveenEric Eldering
Jun 12, 2012·Journal of Molecular Neuroscience : MN·Casandra M CartagenaJitendra R Dave
Nov 15, 2011·Cell Death and Differentiation·M Vogler
Nov 7, 2006·Nature Medicine·Vineet BhandariJack A Elias
May 6, 2006·Cell Death and Differentiation·J Zhuang, H J M Brady
Aug 19, 2011·Molecular & Cellular Proteomics : MCP·Yun XiangJohn M Koomen
Aug 31, 2006·The Journal of Experimental Medicine·Vicki P Losick, Ralph R Isberg
Jan 10, 2012·American Journal of Respiratory Cell and Molecular Biology·Vineet BhandariJack A Elias
Jan 1, 2004·The Journal of Clinical Investigation·Liqun ZhangSusan J Vannucci
Nov 15, 2005·The Journal of Clinical Investigation·Bing MaJack A Elias
Dec 17, 2008·Theoretical Biology & Medical Modelling·Heather A HarringtonK C Tung
Jun 13, 2008·PLoS Biology·Lieven P BillenDavid W Andrews
Aug 23, 2011·PloS One·Sumedha W KarmarkarShelley A Tischkau
May 24, 2012·International Journal of Nanomedicine·Liangran GuoXinguo Jiang
Nov 28, 2013·Neurotoxicity Research·Senthilvelan ManoharRichard Salvi
Mar 15, 2006·Critical Reviews in Clinical Laboratory Sciences·Hellinida Thomadaki, Andreas Scorilas
Feb 2, 2006·Immunological Reviews·Iannis AifantisTomas Vilimas
Aug 19, 2006·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Esther H J WissinkMarcel Verheij
May 5, 2005·The International Journal of Biochemistry & Cell Biology·Weihong YinHinrich Gronemeyer
Mar 19, 2013·Biochimica Et Biophysica Acta·Renata P GuedesChristiane Ferran
Nov 22, 2011·Expert Opinion on Therapeutic Patents·Jae-Hwan KwakHeesoon Lee
Jun 27, 2015·Diagnostic Pathology·Anatolii Romaniuk, Mykola Lуndіn

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