The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Gregory A Mignery - One of the best experts on this subject based on the ideXlab platform.
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the bh4 domain of Bcl 2 inhibits er calcium release and apoptosis by binding the regulatory and coupling domain of the ip3 receptor
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Yi Ping Rong, Fei Zhong, Llewelyn H Roderick, Martin D Bootman, Gregory A Mignery, Geert Bultynck, Ademuyiwa S Aromolaran, Jan B Parys, Humbert De Smedt, Clark W DistelhorstAbstract:Although the presence of a BH4 domain distinguishes the antiapoptotic Protein Bcl-2 from its proapoptotic relatives, little is known about its function. BH4 deletion converts Bcl-2 into a proapoptotic Protein, whereas a TAT-BH4 fusion peptide inhibits apoptosis and improves survival in models of disease due to accelerated apoptosis. Thus, the BH4 domain has antiapoptotic activity independent of full-length Bcl-2. Here we report that the BH4 domain mediates interaction of Bcl-2 with the inositol 1,4,5-trisphosphate (IP3) receptor, an IP3-gated Ca2+ channel on the endoplasmic reticulum (ER). BH4 peptide binds to the regulatory and coupling domain of the IP3 receptor and inhibits IP3-dependent channel opening, Ca2+ release from the ER, and Ca2+-mediated apoptosis. A peptide inhibitor of Bcl-2-IP3 receptor interaction prevents these BH4-mediated effects. By inhibiting proapoptotic Ca2+ signals at their point of origin, the Bcl-2 BH4 domain has the facility to block diverse pathways through which Ca2+ induces apoptosis.
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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
Journal of Cell Biology, 2004Co-Authors: Ruirui Chen, Ignacio Valencia, Fei Zhong, Karen S Mccoll, Llewelyn H Roderick, Martin D Bootman, Michael J Berridge, Stuart J Conway, Andrew B Holmes, Gregory A MigneryAbstract:Inositol 1,4,5-trisphosphate (InsP3) receptors (InsP3Rs) are channels responsible for calcium release from the endoplasmic reticulum (ER). We show that the anti-apoptotic Protein Bcl-2 (either wild type or selectively localized to the ER) significantly inhibited InsP3-mediated calcium release and elevation of cytosolic calcium in WEHI7.2 T cells. This inhibition was due to an effect of Bcl-2 at the level of InsP3Rs because responses to both anti-CD3 antibody and a cell-permeant InsP3 ester were decreased. Bcl-2 inhibited the extent of calcium release from the ER of permeabilized WEHI7.2 cells, even at saturating concentrations of InsP3, without decreasing luminal calcium concentration. Furthermore, Bcl-2 reduced the open probability of purified InsP3Rs reconstituted into lipid bilayers. Bcl-2 and InsP3Rs were detected together in macromolecular complexes by coimmunoprecipitation and blue native gel electrophoresis. We suggest that this functional interaction of Bcl-2 with InsP3Rs inhibits InsP3R activation and thereby regulates InsP3-induced calcium release from the ER.
Guido Kroemer - One of the best experts on this subject based on the ideXlab platform.
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crosstalk between apoptosis and autophagy within the beclin 1 interactome
The EMBO Journal, 2010Co-Authors: Maria Chiara Maiuri, Alfredo Criollo, Guido KroemerAbstract:Although the essential genes for autophagy (Atg) have been identified, the molecular mechanisms through which Atg Proteins control 'self eating' in mammalian cells remain elusive. Beclin 1 (Bec1), the mammalian orthologue of yeast Atg6, is part of the class III phosphatidylinositol 3-kinase (PI3K) complex that induces autophagy. The first among an increasing number of Bec1-interacting Proteins that has been identified is the anti-apoptotic Protein Bcl-2. The dissociation of Bec1 from Bcl-2 is essential for its autophagic activity, and Bcl-2 only inhibits autophagy when it is present in the endoplasmic reticulum (ER). A paper in this issue of the EMBO Journal has identified a novel Protein, NAF-1 (nutrient-deprivation autophagy factor-1), that binds Bcl-2 at the ER. NAF-1 is a component of the inositol-1,4,5 trisphosphate (IP3) receptor complex, which contributes to the interaction of Bcl-2 with Bec1 and is required for Bcl-2 to functionally antagonize Bec1-mediated autophagy. This work provides mechanistic insights into how autophagy- and apoptosis-regulatory molecules crosstalk at the ER.
Martin D Bootman - One of the best experts on this subject based on the ideXlab platform.
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the bh4 domain of Bcl 2 inhibits er calcium release and apoptosis by binding the regulatory and coupling domain of the ip3 receptor
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Yi Ping Rong, Fei Zhong, Llewelyn H Roderick, Martin D Bootman, Gregory A Mignery, Geert Bultynck, Ademuyiwa S Aromolaran, Jan B Parys, Humbert De Smedt, Clark W DistelhorstAbstract:Although the presence of a BH4 domain distinguishes the antiapoptotic Protein Bcl-2 from its proapoptotic relatives, little is known about its function. BH4 deletion converts Bcl-2 into a proapoptotic Protein, whereas a TAT-BH4 fusion peptide inhibits apoptosis and improves survival in models of disease due to accelerated apoptosis. Thus, the BH4 domain has antiapoptotic activity independent of full-length Bcl-2. Here we report that the BH4 domain mediates interaction of Bcl-2 with the inositol 1,4,5-trisphosphate (IP3) receptor, an IP3-gated Ca2+ channel on the endoplasmic reticulum (ER). BH4 peptide binds to the regulatory and coupling domain of the IP3 receptor and inhibits IP3-dependent channel opening, Ca2+ release from the ER, and Ca2+-mediated apoptosis. A peptide inhibitor of Bcl-2-IP3 receptor interaction prevents these BH4-mediated effects. By inhibiting proapoptotic Ca2+ signals at their point of origin, the Bcl-2 BH4 domain has the facility to block diverse pathways through which Ca2+ induces apoptosis.
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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
Journal of Cell Biology, 2004Co-Authors: Ruirui Chen, Ignacio Valencia, Fei Zhong, Karen S Mccoll, Llewelyn H Roderick, Martin D Bootman, Michael J Berridge, Stuart J Conway, Andrew B Holmes, Gregory A MigneryAbstract:Inositol 1,4,5-trisphosphate (InsP3) receptors (InsP3Rs) are channels responsible for calcium release from the endoplasmic reticulum (ER). We show that the anti-apoptotic Protein Bcl-2 (either wild type or selectively localized to the ER) significantly inhibited InsP3-mediated calcium release and elevation of cytosolic calcium in WEHI7.2 T cells. This inhibition was due to an effect of Bcl-2 at the level of InsP3Rs because responses to both anti-CD3 antibody and a cell-permeant InsP3 ester were decreased. Bcl-2 inhibited the extent of calcium release from the ER of permeabilized WEHI7.2 cells, even at saturating concentrations of InsP3, without decreasing luminal calcium concentration. Furthermore, Bcl-2 reduced the open probability of purified InsP3Rs reconstituted into lipid bilayers. Bcl-2 and InsP3Rs were detected together in macromolecular complexes by coimmunoprecipitation and blue native gel electrophoresis. We suggest that this functional interaction of Bcl-2 with InsP3Rs inhibits InsP3R activation and thereby regulates InsP3-induced calcium release from the ER.
Fei Zhong - One of the best experts on this subject based on the ideXlab platform.
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the bh4 domain of Bcl 2 inhibits er calcium release and apoptosis by binding the regulatory and coupling domain of the ip3 receptor
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Yi Ping Rong, Fei Zhong, Llewelyn H Roderick, Martin D Bootman, Gregory A Mignery, Geert Bultynck, Ademuyiwa S Aromolaran, Jan B Parys, Humbert De Smedt, Clark W DistelhorstAbstract:Although the presence of a BH4 domain distinguishes the antiapoptotic Protein Bcl-2 from its proapoptotic relatives, little is known about its function. BH4 deletion converts Bcl-2 into a proapoptotic Protein, whereas a TAT-BH4 fusion peptide inhibits apoptosis and improves survival in models of disease due to accelerated apoptosis. Thus, the BH4 domain has antiapoptotic activity independent of full-length Bcl-2. Here we report that the BH4 domain mediates interaction of Bcl-2 with the inositol 1,4,5-trisphosphate (IP3) receptor, an IP3-gated Ca2+ channel on the endoplasmic reticulum (ER). BH4 peptide binds to the regulatory and coupling domain of the IP3 receptor and inhibits IP3-dependent channel opening, Ca2+ release from the ER, and Ca2+-mediated apoptosis. A peptide inhibitor of Bcl-2-IP3 receptor interaction prevents these BH4-mediated effects. By inhibiting proapoptotic Ca2+ signals at their point of origin, the Bcl-2 BH4 domain has the facility to block diverse pathways through which Ca2+ induces apoptosis.
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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
Journal of Cell Biology, 2004Co-Authors: Ruirui Chen, Ignacio Valencia, Fei Zhong, Karen S Mccoll, Llewelyn H Roderick, Martin D Bootman, Michael J Berridge, Stuart J Conway, Andrew B Holmes, Gregory A MigneryAbstract:Inositol 1,4,5-trisphosphate (InsP3) receptors (InsP3Rs) are channels responsible for calcium release from the endoplasmic reticulum (ER). We show that the anti-apoptotic Protein Bcl-2 (either wild type or selectively localized to the ER) significantly inhibited InsP3-mediated calcium release and elevation of cytosolic calcium in WEHI7.2 T cells. This inhibition was due to an effect of Bcl-2 at the level of InsP3Rs because responses to both anti-CD3 antibody and a cell-permeant InsP3 ester were decreased. Bcl-2 inhibited the extent of calcium release from the ER of permeabilized WEHI7.2 cells, even at saturating concentrations of InsP3, without decreasing luminal calcium concentration. Furthermore, Bcl-2 reduced the open probability of purified InsP3Rs reconstituted into lipid bilayers. Bcl-2 and InsP3Rs were detected together in macromolecular complexes by coimmunoprecipitation and blue native gel electrophoresis. We suggest that this functional interaction of Bcl-2 with InsP3Rs inhibits InsP3R activation and thereby regulates InsP3-induced calcium release from the ER.
Llewelyn H Roderick - One of the best experts on this subject based on the ideXlab platform.
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the bh4 domain of Bcl 2 inhibits er calcium release and apoptosis by binding the regulatory and coupling domain of the ip3 receptor
Proceedings of the National Academy of Sciences of the United States of America, 2009Co-Authors: Yi Ping Rong, Fei Zhong, Llewelyn H Roderick, Martin D Bootman, Gregory A Mignery, Geert Bultynck, Ademuyiwa S Aromolaran, Jan B Parys, Humbert De Smedt, Clark W DistelhorstAbstract:Although the presence of a BH4 domain distinguishes the antiapoptotic Protein Bcl-2 from its proapoptotic relatives, little is known about its function. BH4 deletion converts Bcl-2 into a proapoptotic Protein, whereas a TAT-BH4 fusion peptide inhibits apoptosis and improves survival in models of disease due to accelerated apoptosis. Thus, the BH4 domain has antiapoptotic activity independent of full-length Bcl-2. Here we report that the BH4 domain mediates interaction of Bcl-2 with the inositol 1,4,5-trisphosphate (IP3) receptor, an IP3-gated Ca2+ channel on the endoplasmic reticulum (ER). BH4 peptide binds to the regulatory and coupling domain of the IP3 receptor and inhibits IP3-dependent channel opening, Ca2+ release from the ER, and Ca2+-mediated apoptosis. A peptide inhibitor of Bcl-2-IP3 receptor interaction prevents these BH4-mediated effects. By inhibiting proapoptotic Ca2+ signals at their point of origin, the Bcl-2 BH4 domain has the facility to block diverse pathways through which Ca2+ induces apoptosis.
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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
Journal of Cell Biology, 2004Co-Authors: Ruirui Chen, Ignacio Valencia, Fei Zhong, Karen S Mccoll, Llewelyn H Roderick, Martin D Bootman, Michael J Berridge, Stuart J Conway, Andrew B Holmes, Gregory A MigneryAbstract:Inositol 1,4,5-trisphosphate (InsP3) receptors (InsP3Rs) are channels responsible for calcium release from the endoplasmic reticulum (ER). We show that the anti-apoptotic Protein Bcl-2 (either wild type or selectively localized to the ER) significantly inhibited InsP3-mediated calcium release and elevation of cytosolic calcium in WEHI7.2 T cells. This inhibition was due to an effect of Bcl-2 at the level of InsP3Rs because responses to both anti-CD3 antibody and a cell-permeant InsP3 ester were decreased. Bcl-2 inhibited the extent of calcium release from the ER of permeabilized WEHI7.2 cells, even at saturating concentrations of InsP3, without decreasing luminal calcium concentration. Furthermore, Bcl-2 reduced the open probability of purified InsP3Rs reconstituted into lipid bilayers. Bcl-2 and InsP3Rs were detected together in macromolecular complexes by coimmunoprecipitation and blue native gel electrophoresis. We suggest that this functional interaction of Bcl-2 with InsP3Rs inhibits InsP3R activation and thereby regulates InsP3-induced calcium release from the ER.
