Rong, Yi-Ping; Aromolaran, Ademuyiwa S.; Bultynck, Geert; Zhong, Fei; Li, Xiang; McColl, Karen; Matsuyama, Shigemi; Herlitze, Stephan; Roderick, H. Llewelyn; Bootman, Martin D.; Mignery, Gregory A.; Parys, Jan B.; De Smedt, Humbert and Distelhorst, Clark W.
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|DOI (Digital Object Identifier) Link:||http://dx.doi.org/10.1016/j.molcel.2008.06.014|
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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.
|Item Type:||Journal Article|
|Copyright Holders:||2008 Elsevier Inc.|
|Keywords:||cell cycle; signalling|
|Academic Unit/Department:||Science > Life, Health and Chemical Sciences|
|Depositing User:||Martin Bootman|
|Date Deposited:||24 Oct 2012 13:09|
|Last Modified:||24 Oct 2012 20:47|
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