MEK kinase 1, a substrate for DEVD-directed caspases, is involved in genotoxin-induced apoptosis.

Molecular and Cellular Biology
Christian WidmannG Johnson

Abstract

MEK kinase 1 (MEKK1) is a 196-kDa protein that, in response to genotoxic agents, was found to undergo phosphorylation-dependent activation. The expression of kinase-inactive MEKK1 inhibited genotoxin-induced apoptosis. Following activation by genotoxins, MEKK1 was cleaved in a caspase-dependent manner into an active 91-kDa kinase fragment. Expression of MEKK1 stimulated DEVD-directed caspase activity and induced apoptosis. MEKK1 is itself a substrate for CPP32 (caspase-3). A mutant MEKK1 that is resistant to caspase cleavage was impaired in its ability to induce apoptosis. These findings demonstrate that MEKK1 contributes to the apoptotic response to genotoxins. The regulation of MEKK1 by genotoxins involves its activation, which may be part of survival pathways, followed by its cleavage, which generates a proapoptotic kinase fragment able to activate caspases. MEKK1 and caspases are predicted to be part of an amplification loop to increase caspase activity during apoptosis.

References

Oct 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·D J PickupW K Joklik
Nov 24, 1995·Science·Z XiaM E Greenberg
Dec 1, 1995·The Journal of Experimental Medicine·L A Casciola-RosenA Rosen
Jul 14, 1995·The Journal of Biological Chemistry·D R BeidlerV M Dixit
Sep 26, 1995·Proceedings of the National Academy of Sciences of the United States of America·Y A LazebnikW C Earnshaw
Jun 1, 1995·Anti-cancer Drugs·R E MeynL Milas
Aug 30, 1994·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·J A HickmanT C Fisher
Sep 2, 1994·Science·C A Lange-Carter, G L Johnson
May 10, 1996·The Journal of Biological Chemistry·S NaD E Danley
May 28, 1996·Proceedings of the National Academy of Sciences of the United States of America·S XuM H Cobb
Jun 14, 1996·Cell·A Fraser, G Evan
Aug 30, 1996·The Journal of Biological Chemistry·K OrthV M Dixit
Oct 4, 1996·Cell·P A Baeuerle, D Baltimore
Oct 18, 1996·Cell·E S AlnemriJ Yuan
Mar 21, 1997·The Journal of Biological Chemistry·Q ZhouG S Salvesen
Jun 13, 1997·The Journal of Biological Chemistry·P ErhardtG M Cooper

❮ Previous
Next ❯

Citations

Sep 1, 2007·FEBS Letters·Bing YeRichard L Huganir
Feb 7, 2001·The Journal of Experimental Medicine·V JesenbergerM Baccarini
Dec 14, 2007·Neurochemistry International·Marina VacottoSara Fiszer de Plazas
May 15, 2007·Experimental Cell Research·Normand MarceauFrans C S Ramaekers
Jun 15, 2004·Experimental Cell Research·Bert SchutteFrans C S Ramaekers
Nov 4, 2006·Seminars in Cancer Biology·Go FujinoHidenori Ichijo
Aug 8, 2006·The Journal of Steroid Biochemistry and Molecular Biology·Ruth KorenAmiram Ravid
Mar 15, 2006·Experimental Cell Research·Linda Strandberg IhrlundMaria C Shoshan
May 11, 2005·Biochemical and Biophysical Research Communications·Francisco J MendozaSpencer B Gibson
Apr 23, 2015·Genes, Chromosomes & Cancer·David S NelsonBarrett J Rollins
Jan 18, 2011·Experimental Cell Research·Mahesh VaishnavMartin Dickens
Jun 13, 2015·Biological Research·Mohamed M HafezOthman A Al-Shabanah
Jun 5, 2008·Cell Stem Cell·Viktor JanzenDavid T Scadden
Sep 10, 2009·Cell·Manabu Kurokawa, Sally Kornbluth
Jul 21, 2006·Advances in Enzyme Regulation·Xiaoling Tang, Keqiang Ye
Jun 5, 2012·Molecular Cell·Moon-Chang ChoiTso-Pang Yao
Jun 29, 2000·Annual Review of Biochemistry·W C EarnshawS H Kaufmann
Jun 25, 2003·Biochemical and Biophysical Research Communications·Atsushi EnomotoYoshio Hosoi
Sep 4, 2015·PloS One·Nabil Ben MessaoudJosé M López
Jan 24, 2006·Journal of Molecular and Cellular Cardiology·David C ZebrowskiJunichi Sadoshima
Jun 8, 1999·Annual Review of Immunology·J C Rathmell, C B Thompson
Apr 10, 2004·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Rolf Jakobi
May 25, 2002·British Journal of Haematology·Alessandra M A Di Bacco, Thomas G Cotter
Sep 11, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Sten OrreniusBoris Zhivotovsky
Aug 23, 2001·Proceedings of the National Academy of Sciences of the United States of America·S UraY Gotoh
Aug 15, 2002·Proceedings of the National Academy of Sciences of the United States of America·Pasan FernandoLynn A Megeney
Apr 20, 2004·Journal of Cellular Physiology·William F HolmesKenneth J Soprano
Dec 3, 2014·Cellular Signalling·Laiqun ZhangHasem Habelhah
Aug 13, 2002·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Christian Lesuisse, Lee J Martin
Dec 7, 2000·Molecular Carcinogenesis·J Wang, E Friedman
Nov 25, 2003·Oncogene·Alexei DegterevJunying Yuan

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis