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.
(2008).
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| DOI (Digital Object Identifier) Link: | http://dx.doi.org/doi:10.1016/j.molcel.2008.06.014 |
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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.
| Item Type: | Journal Article |
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| Copyright Holders: | 2008 Elsevier Inc. |
| ISSN: | 1097-4164 |
| Keywords: | cell cycle; signalling |
| Academic Unit/Department: | Science > Life, Health and Chemical Sciences |
| Related URLs: | |
| Item ID: | 34868 |
| Depositing User: | Martin Bootman |
| Date Deposited: | 24 Oct 2012 13:09 |
| Last Modified: | 24 Oct 2012 20:47 |
| URI: | http://oro.open.ac.uk/id/eprint/34868 |
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