Caspase-2 is required for cell death induced by cytoskeletal disruption

Oncogene
L H HoSharad Kumar

Abstract

Caspase-2 is one of the most conserved caspases, yet its biological function remains a matter of controversy. In the present article we analysed mouse embryonic fibroblasts (MEFs) from caspase-2 knockout mice for their sensitivity to various apoptosis inducing agents. We found that cell death induced by drugs that disrupt cytoskeleton is significantly inhibited in Casp2(-/-) MEFs. These drugs included zoledronic acid, vincristine, cytochalasin D and paclitaxel. We demonstrate that MEFs lacking Casp2 show clonogenic survival following drug treatment, whereas all Casp2(+/+) MEFs die, indicating that caspase-2 is required for apoptosis induced by cytoskeletal disruption. We further found that caspase-2 mediates apoptosis via Piddosome, Bid and Bax activation, and cytochrome c release. In the absence of caspase-2, Bid and Bax activation, and cytochrome c release are significantly delayed following drug treatment. Our data provide strong support for a context-dependent function of caspase-2 in apoptosis.

References

Jun 30, 1992·Biochemical and Biophysical Research Communications·S KumarM Noda
May 16, 1997·The Journal of Biological Chemistry·N L HarveyS Kumar
Jun 6, 1998·Genes & Development·L BergeronJ Yuan
Oct 3, 1998·The Journal of Biological Chemistry·P A ColussiS Kumar
Apr 14, 1999·Proceedings of the National Academy of Sciences of the United States of America·L DorstynS Kumar
Mar 14, 2000·Cell Death and Differentiation·L M Shearwin-WhyattS Kumar
Jan 4, 2001·Cell Death and Differentiation·S Kumar, J Doumanis
Apr 17, 2001·Biochemical and Biophysical Research Communications·L Shearwin-WhyattS Kumar
Feb 2, 2002·The Journal of Biological Chemistry·Gabriela ParoniClaudio Brancolini
Feb 8, 2002·The Journal of Biological Chemistry·Yin GuoEmad S Alnemri
Apr 20, 2002·Cell Death and Differentiation·M LamkanfiP Vandenabeele
Jun 18, 2002·The Journal of Biological Chemistry·John D RobertsonSten Orrenius
Aug 24, 2002·Science·Sharad Kumar, David L Vaux
May 2, 2003·Expert Review of Anticancer Therapy·Richard L Theriault
Jun 20, 2003·Cell Death and Differentiation·N J Waterhouse, J A Trapani
Nov 25, 2003·Oncogene·Alexei DegterevJunying Yuan
Dec 10, 2003·Oncogene·Kapil N Bhalla
Jun 24, 2004·The Journal of Cell Biology·Vanessa S MarsdenAndreas Strasser
Jul 13, 2004·Biochimica Et Biophysica Acta·Stuart S Martin, Kristiina Vuori
Aug 7, 2004·Cell Death and Differentiation·B C BaligaS Kumar
Oct 2, 2004·The Oncologist·Jonathan R Green
Feb 26, 2005·Journal of Cell Science·Krister WennerbergChanning J Der
May 4, 2005·Biochemical and Biophysical Research Communications·Boris Zhivotovsky, Sten Orrenius
Jun 16, 2005·Nature Reviews. Molecular Cell Biology·Valentina Perissi, Michael G Rosenfeld
Oct 20, 2005·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Jennifer Y Kong, Simon W Rabkin
Feb 24, 2006·Molecular Biology of the Cell·Christine BonzonDonald D Newmeyer
Apr 19, 2006·The Journal of Biological Chemistry·Rania S Milleron, Shawn B Bratton
Aug 19, 2006·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·René HandrickVerena Jendrossek
Sep 9, 2006·Microbiology and Molecular Biology Reviews : MMBR·Yu-Ling Shih, Lawrence Rothfield
Oct 19, 2006·Current Opinion in Cell Biology·Antonella Antignani, Richard J Youle
Nov 4, 2006·Cell Death and Differentiation·S Kumar
Jan 20, 2007·The EMBO Journal·Oliver KeppThomas Rudel
Feb 20, 2007·Molecular Cancer Therapeutics·Nizar M MhaidatPeter Hersey

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Citations

Apr 26, 2008·Apoptosis : an International Journal on Programmed Cell Death·Lilian SewingRüdiger Göke
Sep 9, 2008·Apoptosis : an International Journal on Programmed Cell Death·Richard A Lockshin
May 30, 2009·Apoptosis : an International Journal on Programmed Cell Death·Tanja KitevskaChristine J Hawkins
Jul 4, 2009·Apoptosis : an International Journal on Programmed Cell Death·Ira R KimPamela S Ohashi
Nov 22, 2008·Cell Death and Differentiation·G KrumschnabelA Villunger
Nov 15, 2011·Cell Death and Differentiation·L Bouchier-Hayes, D R Green
Apr 14, 2012·Cell Death and Differentiation·L DorstynS Kumar
May 7, 2013·Cell Death and Differentiation·M J ParsonsD R Green
Jul 3, 2013·Cell Death and Differentiation·J PucciniS Kumar
Jan 13, 2012·Cell Death & Disease·M SifringerU Felderhoff-Mueser
Jun 17, 2011·Cell Death & Disease·Z AhmedA Logan
Dec 7, 2013·Cell Death & Disease·H Vakifahmetoglu-NorbergB Zhivotovsky
Mar 13, 2009·Proceedings of the National Academy of Sciences of the United States of America·Lien Ha HoSharad Kumar
Jul 21, 2009·Proceedings of the National Academy of Sciences of the United States of America·Akira NakajimaTomohiko Tamura
Feb 26, 2010·Oligonucleotides·Crispin R DassPeter F M Choong
May 16, 2013·Cancer Cell International·Michael JelínekJan Kovář
Jan 16, 2014·PloS One·Indra M MahajanShawn B Bratton
Dec 3, 2013·Cell Death and Differentiation·J J SandowP G Ekert
Mar 9, 2013·Future Oncology·Veronika BrynychováPavel Souček
Aug 22, 2014·Cell Death & Disease·L DorstynS Kumar
Apr 16, 2010·Canadian Journal of Physiology and Pharmacology·Ying Liu, Douglas M Templeton
Jan 6, 2016·The Journal of Pharmacy and Pharmacology·Věra KrálováLenka Skálová
Apr 15, 2009·The Journal of Cell Biology·Claudia ManzlAndreas Villunger
Dec 17, 2009·Expert Opinion on Pharmacotherapy·Michele CaragliaAlberto Abbruzzese
Mar 10, 2010·Experimental Cell Research·Boris Zhivotovsky, Sten Orrenius
Jan 12, 2010·Trends in Cell Biology·Helin Vakifahmetoglu-Norberg, Boris Zhivotovsky
Jul 11, 2008·Journal of Cellular Physiology·Francesco FabbriRosella Silvestrini
May 4, 2011·Journal of Cellular Biochemistry·Lindsay M CoeLaura R McCabe
Feb 18, 2010·Journal of Cellular and Molecular Medicine·Lisa Bouchier-Hayes
Sep 12, 2015·Apoptosis : an International Journal on Programmed Cell Death·Kanwal AhmedTakashi Kondo
Feb 17, 2015·Cancer Cell International·Michael JelínekJan Kovář
Jun 1, 2014·Autophagy·Meenakshi TiwariBrian Herman
Sep 29, 2009·Molecular Cell·Lisa Bouchier-HayesDouglas R Green

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