Serine protease inhibitor 2A inhibits caspase-independent cell death

FEBS Letters
Ni LiuP G Ashton-Rickardt

Abstract

The release of cysteine cathepsins from the lysosome into the cytoplasm can trigger programs of cell death (PCD) that do not require caspase executioner proteases but instead are mediated by toxic reactive oxygen species (ROS). Here, we show that a cytoplasmic inhibitor of papain-like cathepsins - Serine protease inhibitor 2A (Spi2A) - is required for the protection of cells from caspase-independent PCD triggered by tumor necrosis factor-alpha. In the absence of caspase activity, Spi2A suppressed PCD by inhibiting cathepsin B after it was released into the cytoplasm. Spi2A also directly protected against ROS-mediated PCD, which is consistent with a role in suppressing caspase-independent pathways of PCD. We conclude that inhibition of lysosomal executioner proteases by Spi2A is a physiological mechanism by which cells are protected from caspase-independent programmed cell death.

References

Jan 1, 1980·International Review of Cytology·A H WyllieA R Currie
Jan 1, 1981·Methods in Enzymology·A J Barrett, H Kirschke
Aug 29, 1995·Proceedings of the National Academy of Sciences of the United States of America·V GoossensW Fiers
Nov 1, 1995·Free Radical Biology & Medicine·K Ollinger, U T Brunk
Jun 6, 1998·The Journal of Experimental Medicine·D VercammenP Vandenabeele
Jun 25, 1999·Cell Death and Differentiation·C Borner, L Monney
Feb 26, 2000·Carcinogenesis·S W Lowe, A W Lin
Nov 21, 2001·Nature Cell Biology·K F Ferri, G Kroemer
Mar 5, 2002·Nature Immunology·Michael Karin, Anning Lin
Apr 30, 2003·Nature Immunology·Marja Jäättelä, Jürg Tschopp
Oct 1, 2003·The EMBO Journal·Ni LiuPhilip G Ashton-Rickardt

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Citations

Oct 18, 2008·Parasitology Research·Jin-Hee HwangTong-Soo Kim
Jul 17, 2008·Immunologic Research·Timothy W Hand, Susan M Kaech
Aug 18, 2004·Nature Immunology·Ni LiuPhilip G Ashton-Rickardt
Oct 29, 2008·Oncogene·P Boya, G Kroemer
Feb 23, 2010·Current Opinion in Hematology·Don M WojchowskiArvind Dev
Mar 20, 2008·Blood·Pradeep SathyanarayanaDon M Wojchowski
Jun 8, 2007·Biological Chemistry·Veronika StokaBoris Turk
Jan 1, 2011·Case Reports in Obstetrics and Gynecology·Anis FadhlaouiFethi Zhioua
Feb 24, 2006·Proceedings of the National Academy of Sciences of the United States of America·Chance John LuckeyDiane Mathis
Jan 25, 2008·Trends in Cell Biology·Stefan J Marciniak, David A Lomas
Jun 12, 2010·Immunological Reviews·Philip G Ashton-Rickardt
Apr 6, 2016·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Stefanie SantosAna R Álvaro
Apr 30, 2013·Immunology Letters·Philip G Ashton-Rickardt
Oct 25, 2008·Biochimica Et Biophysica Acta·Thomas Kirkegaard, Marja Jäättelä
Nov 26, 2009·Nature Reviews. Immunology·Phillip I BirdJosé A Villadangos
Oct 1, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Abdallah M AbdallahPeter J Peters
Nov 15, 2007·Physiological Genomics·Jose-Luis Gonzalez de AguilarJean-Philippe Loeffler
Oct 3, 2008·The Journal of Pharmacology and Experimental Therapeutics·Timo WeilandAlbrecht Wendel
Jul 3, 2021·Science Signaling·Minjun SonSavaş Tay

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