Coupling endoplasmic reticulum stress to the cell death program. An Apaf-1-independent intrinsic pathway

The Journal of Biological Chemistry
Rammohan V RaoH Michael Ellerby

Abstract

Accumulation of misfolded proteins and alterations in Ca2+ homeostasis in the endoplasmic reticulum (ER) causes ER stress and leads to cell death. However, the signal-transducing events that connect ER stress to cell death pathways are incompletely understood. To discern the pathway by which ER stress-induced cell death proceeds, we performed studies on Apaf-1(-/-) (null) fibroblasts that are known to be relatively resistant to apoptotic insults that induce the intrinsic apoptotic pathway. While these cells were resistant to cell death initiated by proapoptotic stimuli such as tamoxifen, they were susceptible to apoptosis induced by thapsigargin and brefeldin-A, both of which induce ER stress. This pathway was inhibited by catalytic mutants of caspase-12 and caspase-9 and by a peptide inhibitor of caspase-9 but not by caspase-8 inhibitors. Cleavage of caspases and poly(ADP-ribose) polymerase was observed in cell-free extracts lacking cytochrome c that were isolated from thapsigargin or brefeldin-treated cells. To define the molecular requirements for this Apaf-1 and cytochrome c-independent apoptosis pathway further, we developed a cell-free system of ER stress-induced apoptosis; the addition of microsomes prepared from ER stre...Continue Reading

References

Oct 18, 1996·Cell·E S AlnemriJ Yuan
Mar 21, 1997·The Journal of Biological Chemistry·Q ZhouG S Salvesen
Aug 28, 1998·Science·A Ashkenazi, V M Dixit
Feb 26, 1999·The Journal of Biological Chemistry·K OzawaM Tohyama
Jun 11, 1999·The Journal of Biological Chemistry·A SalehE S Alnemri
Jul 10, 1999·The Journal of Biological Chemistry·B B Wolf, D R Green
Sep 2, 1999·Nature Medicine·H M EllerbyR Pasqualini
Dec 28, 1999·Annual Review of Cell and Developmental Biology·I BudihardjoX Wang
Feb 15, 2000·The Journal of Biological Chemistry·B T ChuaP Li
May 16, 2000·The Journal of Biological Chemistry·R C KoyaN Kuzumaki
May 29, 2000·The Journal of Biological Chemistry·S LankiewiczJ H Prehn
Jun 29, 2000·Annual Review of Biochemistry·W C EarnshawS H Kaufmann
Aug 23, 2000·The Journal of Cell Biology·K NakamuraM Michalak
Dec 20, 2000·Proceedings of the National Academy of Sciences of the United States of America·S SperandioD E Bredesen
Mar 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·C ForcetP Mehlen
May 18, 2001·The Journal of Biological Chemistry·D ChauhanK C Anderson
Jul 13, 2001·The Journal of Biological Chemistry·R V RaoD E Bredesen
Aug 3, 2001·Nature Reviews. Molecular Cell Biology·M Leist, M Jäättelä

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Citations

Dec 24, 2005·Apoptosis : an International Journal on Programmed Cell Death·R KimS Murakami
Oct 13, 2006·Apoptosis : an International Journal on Programmed Cell Death·Rong XiangYipeng Qi
Apr 19, 2007·Apoptosis : an International Journal on Programmed Cell Death·Krishnaraj RajalingamThomas Rudel
Aug 19, 2007·Apoptosis : an International Journal on Programmed Cell Death·Surajit KarmakarSwapan K Ray
May 22, 2008·Apoptosis : an International Journal on Programmed Cell Death·Jason BakhshiRammohan V Rao
Apr 11, 2009·Apoptosis : an International Journal on Programmed Cell Death·Vanya I Rasheva, Pedro M Domingos
Jul 25, 2009·Apoptosis : an International Journal on Programmed Cell Death·Bertrand Mollereau
Jul 20, 2010·Apoptosis : an International Journal on Programmed Cell Death·Juan A MartinezStephen F Larner
Aug 24, 2011·Apoptosis : an International Journal on Programmed Cell Death·Francesca Nicolau-GalmésMaría D Boyano
Sep 1, 2011·Apoptosis : an International Journal on Programmed Cell Death·Hua WangTing Liu
Sep 17, 2005·Journal of Bioenergetics and Biomembranes·Ludivine Walter, György Hajnóczky
Jan 16, 2009·Journal of Molecular Neuroscience : MN·Shankar J ChintaRammohan V Rao
Jun 22, 2011·Journal of Molecular Neuroscience : MN·Karen S PoksayRammohan V Rao
May 2, 2008·Molecular Neurobiology·Shane D Madden, Thomas G Cotter
Apr 13, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Joanna Jakubowicz-GilWojciech Rzeski
Sep 15, 2004·Journal of Chemical Neuroanatomy·Yanjun Ma, Linda M Hendershot
Mar 10, 2004·Neurobiology of Disease·Takeshi HayashiPak H Chan
Jan 20, 2004·Trends in Cell Biology·D Thomas Rutkowski, Randal J Kaufman
Dec 21, 2002·Molecular Immunology·Christoph Borner
Jan 18, 2003·Brain Research. Molecular Brain Research·Wassim ElyamanJacques Hugon
Sep 19, 2003·Seminars in Nephrology·Gur P Kaushal
Mar 27, 2003·Progress in Neuro-psychopharmacology & Biological Psychiatry·Andréa C LeBlanc
Feb 4, 2011·Expert Reviews in Molecular Medicine·Stephen M ColganRichard C Austin
Apr 11, 2012·Molecular Pharmaceutics·Diana C WestPaul J Hergenrother
Oct 30, 2012·Acta Pharmacologica Sinica·Ankur BodaliaMichael F Jackson
Sep 8, 2010·Nature Immunology·Penghua WangErol Fikrig
Dec 2, 2004·Nature Reviews. Cancer·Yanjun Ma, Linda M Hendershot
Nov 26, 2008·Oncogene·R B HamanakaJ A Diehl
Jan 7, 2006·Cell Death and Differentiation·D LindholmL Korhonen
Jan 7, 2006·Cell Death and Differentiation·M Boyce, J Yuan
Jan 7, 2006·Cell Death and Differentiation·A d'AzzoR Sano
Jan 7, 2006·Cell Death and Differentiation·J Wu, R J Kaufman

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