Mtd, a novel Bcl-2 family member activates apoptosis in the absence of heterodimerization with Bcl-2 and Bcl-XL.

The Journal of Biological Chemistry
N InoharaG Nuñez

Abstract

We have identified and characterized Mtd, a novel regulator of apoptosis. Sequence analysis revealed that Mtd is a member of the Bcl-2 family of proteins containing conserved BH1, BH2, BH3, and BH4 regions and a carboxyl-terminal hydrophobic domain. In adult tissues, Mtd mRNA was predominantly detected in the brain, liver, and lymphoid tissues, while in the embryo Mtd mRNA was detected in the liver, thymus, lung, and intestinal epithelium. Expression of Mtd promoted the death of primary sensory neurons, 293T cells and HeLa cells, indicating that Mtd is a proapoptotic protein. Unlike all other known death agonists of the Bcl-2 family, Mtd did not bind significantly to the survival-promoting proteins Bcl-2 or Bcl-XL. Furthermore, apoptosis induced by Mtd was not inhibited by Bcl-2 or Bcl-XL. A Mtd mutant with glutamine substitutions of highly conserved amino acids in the BH3 domain retained its ability to promote apoptosis, further indicating that Mtd does not promote apoptosis by heterodimerizing with Bcl-2 or Bcl-XL. Mtd-induced apoptosis was not blocked by broad range synthetic caspase inhibitors z-VAD-fmk or a viral protein CrmA. Mtd is the first example of a naturally occurring Bcl-2 family member that can activate apoptosis...Continue Reading

References

May 5, 1982·Journal of Molecular Biology·J Kyte, R F Doolittle
Aug 15, 1995·Proceedings of the National Academy of Sciences of the United States of America·T W SedlakS J Korsmeyer
Apr 20, 1995·Nature·T ChittendenB C Guild
May 9, 1995·Proceedings of the National Academy of Sciences of the United States of America·M González-GarcíaG Núñez
Dec 11, 1994·Nucleic Acids Research·M HerrmannJ R Kalden
Jan 1, 1996·Genes & Development·E White
Feb 8, 1996·Nature·E H ChengJ M Hardwick
Nov 15, 1996·Genes & Development·K WangS J Korsmeyer
Dec 10, 1996·Proceedings of the National Academy of Sciences of the United States of America·J XiangS J Korsmeyer
Jan 23, 1997·Nature·A J MinnC B Thompson
May 13, 1997·Proceedings of the National Academy of Sciences of the United States of America·S L SchendelJ C Reed
Jul 18, 1997·Science·B AntonssonJ C Martinou
Nov 5, 1997·The Journal of Biological Chemistry·M AritomiK Morikawa
Nov 14, 1997·Proceedings of the National Academy of Sciences of the United States of America·S Y HsuA J Hsueh
Oct 6, 1997·Proceedings of the National Academy of Sciences of the United States of America·N InoharaG Núñez

❮ Previous
Next ❯

Citations

Apr 11, 2001·Head & Neck·B R Gastman
Jan 21, 2004·Cancer Letters·Sung Hak KimYun Jaie Choi
Jun 5, 2004·Developmental and Comparative Immunology·Cheryl Y BrownPaul E Neiman
Jul 30, 2003·Developmental Biology·Weeteck Yeo, Jean Gautier
Dec 21, 2002·Molecular Immunology·Christoph Borner
Jun 8, 2001·Archives of Medical Research·J V Tapia-Vieyra, J Mas-Oliva
Jun 17, 2000·Progress in Neurobiology·K J BanasiakG G Haddad
Sep 15, 2001·Free Radical Biology & Medicine·N Andrieu-AbadieT Levade
Oct 31, 1998·Current Opinion in Immunology·M E Peter, P H Krammer
Aug 15, 1998·Trends in Cell Biology·A Kelekar, C B Thompson
Jan 28, 2012·Cell Death and Differentiation·F KeT Kaufmann
Feb 23, 2013·Cell Death and Differentiation·N EcheverryT Kaufmann
Feb 19, 2005·Nature Reviews. Immunology·Andreas Strasser
Mar 19, 2005·Cell Death and Differentiation·N SoleymanlouI Caniggia
Jun 15, 2006·The Journal of Biological Chemistry·Jose M RodriguezW Douglas Cress
Jan 7, 1999·The EMBO Journal·Q SongC Vincenz
Jan 23, 1999·Current Opinion in Oncology·J C Reed
Mar 17, 2001·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·K RieneckK Bendtzen
Jun 8, 1999·Annual Review of Immunology·J C Rathmell, C B Thompson
Nov 5, 2002·Annual Review of Immunology·Vanessa S Marsden, Andreas Strasser
Jun 15, 2007·Journal of Zhejiang University. Science. B·Estelle SchmittRichard Bertrand
Apr 12, 2014·Apoptosis : an International Journal on Programmed Cell Death·András BaloghMarianna Pap
Jan 19, 2000·Proceedings of the National Academy of Sciences of the United States of America·T IgakiM Miura
Mar 29, 2000·Proceedings of the National Academy of Sciences of the United States of America·S ShimizuY Tsujimoto
Jul 26, 2005·Annals of Hematology·Katrien VermeulenZwi N Berneman
Mar 15, 2006·Critical Reviews in Clinical Laboratory Sciences·Hellinida Thomadaki, Andreas Scorilas
Sep 4, 2010·Expert Opinion on Emerging Drugs·Asfar S AzmiFazlul H Sarkar
May 28, 2015·Proceedings of the National Academy of Sciences of the United States of America·Marcos A CarpioSamuel G Katz
Jan 16, 2007·Brain Research Reviews·Suresh L MehtaRam Raghubir
Sep 10, 2008·Biochemical Pharmacology·Amir M Hossini, Jürgen Eberle
May 9, 2014·The Biochemical Journal·Daochun LuoMartin Post
Mar 31, 2000·Experimental Cell Research·B Antonsson, J C Martinou
Oct 12, 2013·Autophagy·Manpreet KalkatIsabella Caniggia
Mar 5, 2004·Biochimica Et Biophysica Acta·Mee-Ran Kim, Jonathan L Tilly

❮ Previous
Next ❯

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

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.

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

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