Targeting Bcl-2-IP3 receptor interaction to reverse Bcl-2's inhibition of apoptotic calcium signals

被引：211

作者：

Rong, Yi-Ping ^{[1
,2
]}

Aromolaran, Ademuyiwa S. ^{[4
]}

Bultynck, Geert ^{[5
]}

Zhong, Fei ^{[1
,2
]}

Li, Xiang ^{[3
]}

McColl, Karen ^{[1
,2
]}

Matsuyama, Shigemi ^{[1
,2
]}

Herlitze, Stephan ^{[3
]}

Roderick, H. Llewelyn ^{[6
,7
]}

Bootman, Martin D. ^{[6
]}

Mignery, Gregory A. ^{[4
]}

Parys, Jan B. ^{[5
]}

De Smedt, Humbert ^{[5
]}

Distelhorst, Clark W. ^{[1
,2
]}

机构：

[1] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA

[2] Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA

[3] Case Western Reserve Univ, Dept Neurosci, Cleveland, OH 44106 USA

[4] Loyola Univ, Stritch Sch Med, Dept Physiol, Maywood, IL 60153 USA

[5] Katholieke Univ Leuven, Div Physiol, Mol Signalling Lab, B-3000 Louvain, Belgium

[6] Babraham Inst, Lab Mol & Cellular Signaling, Cambridge CB2 4AT, England

[7] Univ Cambridge, Dept Pharmacol, Cambridge CB2 1PD, England

来源：

MOLECULAR CELL | 2008年 / 31卷 / 02期

基金：

英国生物技术与生命科学研究理事会;

关键词：

D O I：

10.1016/j.molcel.2008.06.014

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：255 / 265

页数：11

共 47 条

[1] Cardiac type 2 inositol 1,4,5-trisphosphate receptor - Interaction and modulation by calcium/calmodulin-dependent protein kinase II [J].

Bare, DJ ;

Kettlun, CS ;

Liang, M ;

Bers, DM ;

Mignery, GA .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (16) :15912-15920

[2] Phosphorylation of BCL-2 regulates ER Ca2+ homeostasis and apoptosis [J].

Bassik, MC ;

Scorrano, L ;

Oakes, SA ;

Pozzan, T ;

Korsmeyer, SJ .

EMBO JOURNAL, 2004, 23 (05) :1207-1216

[3] The versatility and universality of calcium signalling [J].

Berridge, MJ ;

Lipp, P ;

Bootman, MD .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2000, 1 (01) :11-21

[4] The inositol 1,4,5-trisphosphate receptors [J].

Bezprozvanny, I .

CELL CALCIUM, 2005, 38 (3-4) :261-272

[5] Bcl-2 functionally interacts with inositol 1,4,5-trisphosphate receptors to regulate calcium release from the ER in response to inositol 1,4,5-trisphosphate [J].

Chen, R ;

Valencia, I ;

Zhong, F ;

McColl, KS ;

Roderick, HL ;

Bootman, MD ;

Berridge, MJ ;

Conway, SJ ;

Holmes, AB ;

Mignery, GA ;

Velez, P ;

Distelhorst, CW .

JOURNAL OF CELL BIOLOGY, 2004, 166 (02) :193-203

[6] The synthesis of membrane permeant derivatives of myo-inositol 1,4,5-trisphosphate [J].

Conway, Stuart J. ;

Thuring, Jan W. ;

Andreu, Sylvain ;

Kvinlaug, Brynn T. ;

Roderick, H. Llewelyn ;

Bootman, Martin D. ;

Holmes, Andrew B. .

AUSTRALIAN JOURNAL OF CHEMISTRY, 2006, 59 (12) :887-893

[7] The BCL2 family: Regulators of the cellular life-or-death switch [J].

Cory, S ;

Adams, JM .

NATURE REVIEWS CANCER, 2002, 2 (09) :647-656

[8] Cell death: Critical control points [J].

Danial, NN ;

Korsmeyer, SJ .

CELL, 2004, 116 (02) :205-219

[9] Bcl-2 and calcium: controversy beneath the surface [J].

Distelhorst, CW ;

Shore, GC .

ONCOGENE, 2004, 23 (16) :2875-2880

[10] Preassociation of calmodulin with voltage-gated Ca2+ channels revealed by FRET in single living cells [J].

Erickson, MG ;

Alseikhan, BA ;

Peterson, BZ ;

Yue, DT .

NEURON, 2001, 31 (06) :973-985

← 1 2 3 4 5 →