Caspase-mediated activation and induction of apoptosis by the mammalian Ste20-like kinase Mst1

The EMBO Journal
J D GravesE G Krebs

Abstract

Mst1 is a ubiquitously expressed serine-threonine kinase, homologous to the budding yeast Ste20, whose physiological regulation and cellular function are unknown. In this paper we show that Mst1 is specifically cleaved by a caspase 3-like activity during apoptosis induced by either cross-linking CD95/Fas or by staurosporine treatment. CD95/Fas-induced cleavage of Mst1 was blocked by the cysteine protease inhibitor ZVAD-fmk, the more selective caspase inhibitor DEVD-CHO and by the viral serpin CrmA. Caspase-mediated cleavage of Mst1 removes the C-terminal regulatory domain and correlates with an increase in Mst1 activity in vivo, consistent with caspase-mediated cleavage activating Mst1. Overexpression of either wild-type Mst1 or a truncated mutant induces morphological changes characteristic of apoptosis. Furthermore, exogenously expressed Mst1 is cleaved, indicating that Mst1 can activate caspases that result in its cleavage. Kinase-dead Mst1 did not induce morphological alterations and was not cleaved upon overexpression, indicating that Mst1 must be catalytically active in order to mediate these effects. Mst1 activates MKK6, p38 MAPK, MKK7 and SAPK in co-transfection assays, suggesting that Mst1 may activate these pathways. ...Continue Reading

References

Nov 24, 1995·Science·Z XiaM E Greenberg
Dec 1, 1995·The Journal of Experimental Medicine·L A Casciola-RosenA Rosen
Feb 2, 1995·Nature·J DheinP H Krammer
Feb 17, 1995·The Journal of Biological Chemistry·M Tewari, V M Dixit
Mar 10, 1995·Science·S Nagata, P Golstein
Sep 15, 1995·The Journal of Biological Chemistry·C L Creasy, J Chernoff
Feb 9, 1996·The Journal of Biological Chemistry·J HanR J Ulevitch
May 10, 1996·The Journal of Biological Chemistry·S NaD E Danley
May 1, 1996·European Journal of Immunology·D J WilsonR C Budd
Aug 30, 1996·The Journal of Biological Chemistry·C L CreasyJ Chernoff
Sep 17, 1996·Proceedings of the National Academy of Sciences of the United States of America·L K TaylorR L Erikson
Oct 18, 1996·Cell·E S AlnemriJ Yuan
Nov 26, 1996·Proceedings of the National Academy of Sciences of the United States of America·J D GravesE A Clark
Dec 10, 1996·Proceedings of the National Academy of Sciences of the United States of America·S M SrinivasulaE S Alnemri
Feb 1, 1997·Current Opinion in Genetics & Development·G R FangerG L Johnson
Feb 7, 1997·Cell·M D JacobsonM C Raff
Feb 7, 1997·Cell·S Nagata

❮ Previous
Next ❯

Citations

Jul 9, 1998·Pathology Oncology Research : POR·R L RiceJ D Taylor
Apr 29, 2009·Pflügers Archiv : European journal of physiology·Eric Delpire
Jul 23, 2005·Current Osteoporosis Reports·Alfred A Reszka, Gideon A Rodan
Apr 10, 2004·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Rolf Jakobi
Oct 14, 2003·Biochemical Pharmacology·Christian Schwerk, Klaus Schulze-Osthoff
Jun 1, 2000·Advances in Enzyme Regulation·E G Krebs, J D Graves
Aug 24, 1999·Pharmacology & Therapeutics·J D Graves, E G Krebs
Feb 17, 2000·Cellular Signalling·K Ono, J Han
Oct 31, 1998·Current Opinion in Immunology·M E Peter, P H Krammer
Apr 24, 2001·Trends in Cell Biology·I DanA Kusumi
Dec 22, 1999·Trends in Cell Biology·C J Bakal, J E Davies
Mar 9, 2004·Apoptosis : an International Journal on Programmed Cell Death·B McLaughlin
May 11, 2013·Cell Death & Disease·P Sanphui, S C Biswas
Sep 11, 2012·Cellular & Molecular Immunology·Hailei YinZhaocai Zhou
Feb 6, 2007·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Parham MinooAlessandro Lugli
Feb 24, 2007·Nature Reviews. Cancer·Kieran Harvey, Nicolas Tapon
Apr 12, 2006·Nature Reviews. Molecular Cell Biology·Alexander HergovichBrian A Hemmings
May 25, 2007·Nature Reviews. Molecular Cell Biology·Armando van der Horst, Boudewijn M T Burgering
Aug 30, 2011·Oncogene·A MauvielX Varelas
Aug 5, 2005·Oncogene·Sophie LaunayCarmen Garrido
Jul 10, 2001·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·S UraY Gotoh
Feb 27, 2003·European Journal of Biochemistry·Mhairi J FrameNigel J Pyne
Dec 17, 2008·Proceedings of the National Academy of Sciences of the United States of America·Dawang ZhouJoseph Avruch
Aug 14, 2013·Proceedings of the National Academy of Sciences of the United States of America·Ting-Chun Yeh, Shawn B Bratton
Dec 24, 2009·The Journal of Biological Chemistry·Wenzhi BiZengqiang Yuan
Sep 3, 2010·The Journal of Biological Chemistry·Jikyoung ParkSean Bong Lee
Jan 5, 2011·The Journal of Biological Chemistry·Cai GuoGerd P Pfeifer
Jan 8, 2011·The Journal of Biological Chemistry·Fang YuanZengqiang Yuan
Mar 22, 2012·The Journal of Biological Chemistry·Jeong Han KangMichael R Maurizi
Mar 28, 2008·The Journal of Biological Chemistry·Emilio NogueiraCelia M Pombo
Feb 18, 2009·The Journal of Biological Chemistry·Zengqiang YuanAzad Bonni
Dec 19, 2008·The Journal of Biological Chemistry·Joseph AvruchFan Xia
Oct 26, 2010·Antioxidants & Redox Signaling·Kohsuke TakedaHidenori Ichijo
Jul 14, 2010·Antioxidants & Redox Signaling·Maaike C W van den Berg, Boudewijn M T Burgering

❮ 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

© 2022 Meta ULC. All rights reserved