Anti-apoptotic protein Bcl-2 interacts with and destabilizes the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA)

The Biochemical Journal
Elena S DreminaChristian Schöneich

Abstract

The anti-apoptotic effect of Bcl-2 is well established, but the detailed mechanisms are unknown. In the present study, we show in vitro a direct interaction of Bcl-2 with the rat skeletal muscle SERCA (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase), leading to destabilization and inactivation of the protein. Recombinant human Bcl-2D21, a truncated form of Bcl-2 with a deletion of 21 residues at the C-terminal membrane-anchoring region, was expressed and affinity-purified as a glutathione S-transferase fusion protein. Bcl-2D21 co-immunoprecipitated and specifically interacted with SERCA in an in vitro-binding assay. The original level of Bcl-2 in sarcoplasmic reticulum vesicles was very low, i.e. hardly detectable by immunoblotting with specific antibodies. The addition of Bcl-2D21 to the sarcoplasmic reticulum resulted in the inhibition of the Ca2+-ATPase activity dependent on the Bcl-2D21/SERCA molar ratio and incubation time. A complete inactivation of SERCA was observed after 2.5 h of incubation at approx. 2:1 molar ratio of Bcl-2D21 to SERCA. In contrast, Bcl-2D21 did not significantly change the activity of the plasma-membrane Ca2+-ATPase. The redox state of the single Cys158 residue in Bcl-2D21 and the presence of GSH di...Continue Reading

References

Nov 15, 1979·Analytical Biochemistry·P A LanzettaO A Candia
Sep 5, 1991·Nature·G NuñezS J Korsmeyer
Nov 17, 1988·Nature·J C ReedP C Nowell
Oct 22, 1993·Cell·D M HockenberyS J Korsmeyer
Jan 27, 1995·Cell·D E Clapham
Jul 5, 1994·Proceedings of the National Academy of Sciences of the United States of America·M LamC W Distelhorst
Jan 28, 1993·Nature·M J Berridge
Sep 6, 1996·The Journal of Biological Chemistry·Y KimuraD H MacLennan
Feb 1, 1996·Current Opinion in Genetics & Development·S N Farrow, R Brown
May 2, 1997·The Journal of Biological Chemistry·T ItoW S May
Nov 20, 1997·The Journal of Biological Chemistry·D H MacLennanN M Green
Aug 28, 1998·Science·D R Green, J C Reed
Oct 27, 1998·Oncogene·T H KuoW Tsang
May 24, 2000·Proceedings of the National Academy of Sciences of the United States of America·R Foyouzi-YoussefiK H Krause
Jul 13, 2000·Cell Calcium·T S MaG J Gallinghouse
Mar 7, 2001·Antioxidants & Redox Signaling·D W Voehringer, R E Meyn
Jun 20, 2001·Nature Reviews. Molecular Cell Biology·J C Martinou, D R Green
Jun 20, 2001·Nature Reviews. Molecular Cell Biology·M J BerridgeM D Bootman
May 23, 2002·Biochimie·Paolo PintonRosario Rizzuto
May 24, 2003·Annals of the New York Academy of Sciences·David H MacLennanA Russell Tupling
May 1, 1959·Archives of Biochemistry and Biophysics·G L ELLMAN
Nov 11, 2003·Free Radical Biology & Medicine·Jaroslaw KanskiChristian Schöneich

❮ Previous
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Citations

Aug 29, 2013·Archives of Toxicology·Frank Thévenod, Wing-Kee Lee
Apr 17, 2008·Pflügers Archiv : European journal of physiology·Elizabeth VafiadakiDespina Sanoudou
Mar 1, 2008·Cell Death and Differentiation·L GalluzziG Kroemer
Apr 25, 2008·Nature Reviews. Cancer·H Llewelyn Roderick, Simon J Cook
Sep 11, 2009·The Journal of Biological Chemistry·Sanjaya Kumar SahooDo Han Kim
Oct 31, 2008·Molecular Biology of the Cell·Elizabeth VafiadakiEvangelia G Kranias
Mar 29, 2011·Cold Spring Harbor Perspectives in Biology·Ilse VandecaetsbeekJo Vanoevelen
Sep 10, 2010·Cold Spring Harbor Perspectives in Biology·Michael W Harr, Clark W Distelhorst
Jun 30, 2009·Molecular Pharmacology·David HermansonChengguo Xing
Aug 8, 2007·Annual Review of Physiology·Yiping Rong, Clark W Distelhorst
Mar 28, 2008·American Journal of Physiology. Cell Physiology·Voraratt ChampattanachaiJohn C Chatham
Dec 29, 2011·Journal of Allergy·Steven R White
Feb 10, 2009·American Journal of Respiratory and Critical Care Medicine·Shama AhmadCarl W White
Oct 17, 2013·Apoptosis : an International Journal on Programmed Cell Death·Christian SchöneichVictor Sharov
Feb 5, 2013·Cold Spring Harbor Perspectives in Biology·J Marie Hardwick, Lucian Soane
Sep 8, 2012·Cellular and Molecular Life Sciences : CMLS·Giovanni MonacoGeert Bultynck
Mar 10, 2015·International Journal of Molecular Sciences·Norishi Ueda
Jun 21, 2005·International Journal of Radiation Biology·M T SantiniP L Indovina
Jan 17, 2016·Biochimica Et Biophysica Acta·Mart BittremieuxGeert Bultynck
Feb 2, 2017·Cell Calcium·Nadine Hempel, Mohamed Trebak
Jan 14, 2009·Seminars in Cancer Biology·Nathan SusnowDavid M Hockenbery
Nov 12, 2009·BioFactors·Ilse VandecaetsbeekPeter Vangheluwe
Feb 23, 2019·Cell Death & Disease·Chloe F A WarrenNikola A Bowden
Feb 27, 2008·The Journal of Biological Chemistry·Chunyan XuJohn C Reed
Oct 1, 2009·Physiological Reviews·Marisa Brini, Ernesto Carafoli
Sep 11, 2019·Cold Spring Harbor Perspectives in Biology·Jialin ChenPeter Vangheluwe
Jun 1, 2007·Clinical and Vaccine Immunology : CVI·Jason R GrantWilfred A Jefferies
Mar 13, 2009·American Journal of Physiology. Cell Physiology·Eva SzegezdiAfshin Samali
Aug 10, 2016·Biomolecular Concepts·Jozef Hatok, Peter Racay
Sep 5, 2013·Biological Chemistry·Natalia SovolyovaSusan E Logue
Sep 18, 2012·Circulation Research·Chi Keung LamEvangelia G Kranias
Feb 25, 2017·Cell Death and Differentiation·Atan Gross, Samuel G Katz
Apr 11, 2018·Frontiers in Cellular Neuroscience·Tim Vervliet
Jul 15, 2017·Frontiers in Oncology·Jessica J Chen, Darren Boehning
Jun 18, 2020·International Journal of Molecular Sciences·Kevin ZhaiDietrich Büsselberg
Jun 20, 2020·Journal of Bioenergetics and Biomembranes·Iman F Abou-El-Naga

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