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Title: Targeting Bcl-2-IP3 receptor interaction to reverse Bcl-2's inhibition of apoptotic calcium signals
Authors: Rong, Yi-Ping
Aromolaran, Ademuyiwa S
Bultynck, Geert
Zhong, Fei
McColl, Karen
Li, Xiang
Matsuyama, Shigemi
Herlitze, Stephan
Bootman, Martin D
Roderick, H Llewelyn
Mignery, Gregory A
Parys, Jan
De Smedt, Humbert
Distelhorst, Clark W # ×
Issue Date: Jul-2008
Publisher: Cell Press
Series Title: Molecular Cell vol:31 issue:2 pages:255-265
Abstract: The antiapoptotic protein Bcl-2 inhibits Ca2+ release from the endoplasmic reticulum (ER). One proposed mechanism involves an interaction of Bcl-2 with the inositol 1,4,5-trisphosphate receptor (IP3R) Ca2+ channel localized with Bcl-2 on the ER. Here we document Bcl-2-IP3R interaction within cells by FRET and identify a Bcl-2 interacting region in the regulatory and coupling domain of the IP3R. A peptide based on this IP3R sequence displaced Bcl-2 from the IP3R and reversed Bcl-2-mediated inhibition of IP3R channel activity in vitro, IP3-induced ER Ca2+ release in permeabilized cells, and cell-permeable IP3 ester-induced Ca2+ elevation in intact cells. This peptide also reversed Bcl-2's inhibition of T cell receptor-induced Ca2+ elevation and apoptosis. Thus, the interaction of Bcl-2 with IP3Rs contributes to the regulation of proapoptotic Ca2+ signals by Bcl-2, suggesting the Bcl-2-IP3R interaction as a potential therapeutic target in diseases associated with Bcl-2's inhibition of cell death.
URI: 
ISSN: 1097-2765
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Molecular and Cellular Signaling
Laboratory of Biosignaling & Therapeutics
Experimental Cardiology
× corresponding author
# (joint) last author

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