Heat-shock proteins attenuate SERCA inactivation by the anti-apoptotic protein Bcl-2: possible implications for the ER Ca2+-mediated apoptosis.

The Biochemical Journal
Elena S DreminaChristian Schöneich

Abstract

We have demonstrated previously that Bcl-2 and Bcl-2Δ21, a C-terminally truncated Bcl-2 sequence, inactivate SERCA (sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase) 1 in isolated SR (sarcoplasmic reticulum), accompanied by a translocation from CRDs (caveolae-related domains) of the SR. In the present study, we obtained evidence for the interaction of Bcl-2 with SERCA2b in C2C12 myoblasts and HEK (human embryonic kidney)-293 cells. Bcl-2 and SERCA2b co-immunoprecipitated from lysate and microsomal fractions of Bcl-2-overexpressing cells. However, Bcl-2 overexpression resulted only in a slight translocation from the CRDs and no significant SERCA inactivation. In isolated HEK-293 cell microsomes, incubation with Bcl-2Δ21 afforded SERCA2b inactivation and some translocation. HSP (heat-shock protein) 70, HSP90, HSP27 and α-crystallin attenuated Bcl-2Δ21-dependent SERCA2b inactivation. An in vitro mechanistic study with the SERCA1 isoform shows that HSP70 (i) protects SERCA1 from the inactivation by Bcl-2Δ21, (ii) inhibits SERCA1 translocation from CRD fractions, and (iii) prevents the Bcl-2Δ21-dependent loss of FITC labelling. Our data demonstrate that the mechanism of SERCA inactivation by Bcl-2 established in vitro for the SERCA1...Continue Reading

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Citations

Oct 17, 2013·Apoptosis : an International Journal on Programmed Cell Death·Christian SchöneichVictor Sharov
Sep 8, 2012·Cellular and Molecular Life Sciences : CMLS·Giovanni MonacoGeert Bultynck
Jan 17, 2016·Biochimica Et Biophysica Acta·Mart BittremieuxGeert Bultynck
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Aug 10, 2016·Biomolecular Concepts·Jozef Hatok, Peter Racay
Jun 12, 2018·Analytical Cellular Pathology (Amsterdam)·Cailing JiangYuxian Bai
Dec 20, 2020·Animals : an Open Access Journal From MDPI·Abdelrazeq M ShehataWalid S Habashy
Apr 3, 2021·Biochimica Et Biophysica Acta. Molecular Cell Research·Fernanda O LemosJan B Parys

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