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Bcl-2 and IP3 compete for the ligand-binding domain of IP3Rs modulating Ca2+ signaling output.

Ivanova H, Wagner LE 2nd, Tanimura A, Vandermarliere E, Luyten T, Welkenhuyzen K, Alzayady KJ, Wang L, Hamada K, Mikoshiba K, De Smedt H, Martens L, Yule DI, Parys JB, Bultynck G.

Cell Mol Life Sci. 2019 Oct;76(19):3843-3859. doi: 10.1007/s00018-019-03091-8. Epub 2019 Apr 16.


Fundamental insights into autosomal dominant polycystic kidney disease from human-based cell models.

Weydert C, Decuypere JP, De Smedt H, Janssens P, Vennekens R, Mekahli D.

Pediatr Nephrol. 2019 Oct;34(10):1697-1715. doi: 10.1007/s00467-018-4057-5. Epub 2018 Sep 13.


Constitutive IP3 signaling underlies the sensitivity of B-cell cancers to the Bcl-2/IP3 receptor disruptor BIRD-2.

Bittremieux M, La Rovere RM, Akl H, Martines C, Welkenhuyzen K, Dubron K, Baes M, Janssens A, Vandenberghe P, Laurenti L, Rietdorf K, Morciano G, Pinton P, Mikoshiba K, Bootman MD, Efremov DG, De Smedt H, Parys JB, Bultynck G.

Cell Death Differ. 2019 Mar;26(3):531-547. doi: 10.1038/s41418-018-0142-3. Epub 2018 Jun 13.


Polycystin-2-dependent control of cardiomyocyte autophagy.

Criollo A, Altamirano F, Pedrozo Z, Schiattarella GG, Li DL, Rivera-Mejías P, Sotomayor-Flores C, Parra V, Villalobos E, Battiprolu PK, Jiang N, May HI, Morselli E, Somlo S, de Smedt H, Gillette TG, Lavandero S, Hill JA.

J Mol Cell Cardiol. 2018 May;118:110-121. doi: 10.1016/j.yjmcc.2018.03.002. Epub 2018 Mar 6.


Reciprocal sensitivity of diffuse large B-cell lymphoma cells to Bcl-2 inhibitors BIRD-2 versus venetoclax.

Vervloessem T, Akl H, Tousseyn T, De Smedt H, Parys JB, Bultynck G.

Oncotarget. 2017 Dec 4;8(67):111656-111671. doi: 10.18632/oncotarget.22898. eCollection 2017 Dec 19.


A double point mutation at residues Ile14 and Val15 of Bcl-2 uncovers a role for the BH4 domain in both protein stability and function.

Monaco G, La Rovere R, Karamanou S, Welkenhuyzen K, Ivanova H, Vandermarliere E, Di Martile M, Del Bufalo D, De Smedt H, Parys JB, Economou A, Bultynck G.

FEBS J. 2018 Jan;285(1):127-145. doi: 10.1111/febs.14324. Epub 2017 Dec 2.


Everolimus halts hepatic cystogenesis in a rodent model of polycystic-liver-disease.

Temmerman F, Chen F, Libbrecht L, Vander Elst I, Windmolders P, Feng Y, Ni Y, De Smedt H, Nevens F, van Pelt J.

World J Gastroenterol. 2017 Aug 14;23(30):5499-5507. doi: 10.3748/wjg.v23.i30.5499.


DPB162-AE, an inhibitor of store-operated Ca2+ entry, can deplete the endoplasmic reticulum Ca2+ store.

Bittremieux M, Gerasimenko JV, Schuermans M, Luyten T, Stapleton E, Alzayady KJ, De Smedt H, Yule DI, Mikoshiba K, Vangheluwe P, Gerasimenko OV, Parys JB, Bultynck G.

Cell Calcium. 2017 Mar;62:60-70. doi: 10.1016/j.ceca.2017.01.015. Epub 2017 Feb 1.


The trans-membrane domain of Bcl-2α, but not its hydrophobic cleft, is a critical determinant for efficient IP3 receptor inhibition.

Ivanova H, Ritaine A, Wagner L, Luyten T, Shapovalov G, Welkenhuyzen K, Seitaj B, Monaco G, De Smedt H, Prevarskaya N, Yule DI, Parys JB, Bultynck G.

Oncotarget. 2016 Aug 23;7(34):55704-55720. doi: 10.18632/oncotarget.11005.


Altered mTOR signalling in nephropathic cystinosis.

Ivanova EA, van den Heuvel LP, Elmonem MA, De Smedt H, Missiaen L, Pastore A, Mekahli D, Bultynck G, Levtchenko EN.

J Inherit Metab Dis. 2016 May;39(3):457-464. doi: 10.1007/s10545-016-9919-z. Epub 2016 Feb 24.


Efficacy and safety of an adjunctive mGlu2 receptor positive allosteric modulator to a SSRI/SNRI in anxious depression.

Kent JM, Daly E, Kezic I, Lane R, Lim P, De Smedt H, De Boer P, Van Nueten L, Drevets WC, Ceusters M.

Prog Neuropsychopharmacol Biol Psychiatry. 2016 Jun 3;67:66-73. doi: 10.1016/j.pnpbp.2016.01.009. Epub 2016 Jan 20.


BAX inhibitor-1 is a Ca(2+) channel critically important for immune cell function and survival.

Lisak D, Schacht T, Gawlitza A, Albrecht P, Aktas O, Koop B, Gliem M, Hofstetter HH, Zanger K, Bultynck G, Parys JB, De Smedt H, Kindler T, Adams-Quack P, Hahn M, Waisman A, Reed JC, Hövelmeyer N, Methner A.

Cell Death Differ. 2016 Feb;23(2):358-68. doi: 10.1038/cdd.2015.115. Epub 2015 Oct 16.


Autophagy in renal diseases.

De Rechter S, Decuypere JP, Ivanova E, van den Heuvel LP, De Smedt H, Levtchenko E, Mekahli D.

Pediatr Nephrol. 2016 May;31(5):737-52. doi: 10.1007/s00467-015-3134-2. Epub 2015 Jul 4. Review.


Ryanodine receptors are targeted by anti-apoptotic Bcl-XL involving its BH4 domain and Lys87 from its BH3 domain.

Vervliet T, Lemmens I, Vandermarliere E, Decrock E, Ivanova H, Monaco G, Sorrentino V, Nadif Kasri N, Missiaen L, Martens L, De Smedt H, Leybaert L, Parys JB, Tavernier J, Bultynck G.

Sci Rep. 2015 Apr 15;5:9641. doi: 10.1038/srep09641.


Pharmacokinetic and pharmacodynamic characterisation of JNJ-40411813, a positive allosteric modulator of mGluR2, in two randomised, double-blind phase-I studies.

Salih H, Anghelescu I, Kezic I, Sinha V, Hoeben E, Van Nueten L, De Smedt H, De Boer P.

J Psychopharmacol. 2015 Apr;29(4):414-25. doi: 10.1177/0269881115573403. Epub 2015 Mar 3.


The BH4 domain of anti-apoptotic Bcl-XL, but not that of the related Bcl-2, limits the voltage-dependent anion channel 1 (VDAC1)-mediated transfer of pro-apoptotic Ca2+ signals to mitochondria.

Monaco G, Decrock E, Arbel N, van Vliet AR, La Rovere RM, De Smedt H, Parys JB, Agostinis P, Leybaert L, Shoshan-Barmatz V, Bultynck G.

J Biol Chem. 2015 Apr 3;290(14):9150-61. doi: 10.1074/jbc.M114.622514. Epub 2015 Feb 13.


A dual role for the anti-apoptotic Bcl-2 protein in cancer: mitochondria versus endoplasmic reticulum.

Akl H, Vervloessem T, Kiviluoto S, Bittremieux M, Parys JB, De Smedt H, Bultynck G.

Biochim Biophys Acta. 2014 Oct;1843(10):2240-52. doi: 10.1016/j.bbamcr.2014.04.017. Epub 2014 Apr 21. Review.


Bcl-2 binds to and inhibits ryanodine receptors.

Vervliet T, Decrock E, Molgó J, Sorrentino V, Missiaen L, Leybaert L, De Smedt H, Kasri NN, Parys JB, Bultynck G.

J Cell Sci. 2014 Jun 15;127(Pt 12):2782-92. doi: 10.1242/jcs.150011. Epub 2014 Apr 24.


Inositol 1,4,5-trisphosphate receptor-isoform diversity in cell death and survival.

Ivanova H, Vervliet T, Missiaen L, Parys JB, De Smedt H, Bultynck G.

Biochim Biophys Acta. 2014 Oct;1843(10):2164-83. doi: 10.1016/j.bbamcr.2014.03.007. Epub 2014 Mar 15. Review.


Measurement of intracellular Ca2+ release in intact cells using 45Ca2+.

Luyten T, Bultynck G, Parys JB, De Smedt H, Missiaen L.

Cold Spring Harb Protoc. 2014 Mar 1;2014(3):284-8. doi: 10.1101/pdb.prot073197.


Measurement of intracellular Ca2+ release in permeabilized cells using 45Ca2+.

Luyten T, Bultynck G, Parys JB, De Smedt H, Missiaen L.

Cold Spring Harb Protoc. 2014 Mar 1;2014(3):289-94. doi: 10.1101/pdb.prot073189.


Measurement of intracellular Ca2+ release in intact and permeabilized cells using 45Ca2+.

Missiaen L, Luyten T, Bultynck G, Parys JB, De Smedt H.

Cold Spring Harb Protoc. 2014 Mar 1;2014(3):263-70. doi: 10.1101/pdb.top066126.


Polycystin-1 but not polycystin-2 deficiency causes upregulation of the mTOR pathway and can be synergistically targeted with rapamycin and metformin.

Mekahli D, Decuypere JP, Sammels E, Welkenhuyzen K, Schoeber J, Audrezet MP, Corvelyn A, Dechênes G, Ong AC, Wilmer MJ, van den Heuvel L, Bultynck G, Parys JB, Missiaen L, Levtchenko E, De Smedt H.

Pflugers Arch. 2014 Aug;466(8):1591-604. doi: 10.1007/s00424-013-1394-x. Epub 2013 Nov 6.


Alpha-helical destabilization of the Bcl-2-BH4-domain peptide abolishes its ability to inhibit the IP3 receptor.

Monaco G, Decrock E, Nuyts K, Wagner LE 2nd, Luyten T, Strelkov SV, Missiaen L, De Borggraeve WM, Leybaert L, Yule DI, De Smedt H, Parys JB, Bultynck G.

PLoS One. 2013 Aug 30;8(8):e73386. doi: 10.1371/journal.pone.0073386. eCollection 2013.


Bax Inhibitor-1-mediated Ca2+ leak is decreased by cytosolic acidosis.

Kiviluoto S, Luyten T, Schneider L, Lisak D, Rojas-Rivera D, Welkenhuyzen K, Missaen L, De Smedt H, Parys JB, Hetz C, Methner A, Bultynck G.

Cell Calcium. 2013 Sep;54(3):186-92. doi: 10.1016/j.ceca.2013.06.002. Epub 2013 Jul 16.


IP3R2 levels dictate the apoptotic sensitivity of diffuse large B-cell lymphoma cells to an IP3R-derived peptide targeting the BH4 domain of Bcl-2.

Akl H, Monaco G, La Rovere R, Welkenhuyzen K, Kiviluoto S, Vervliet T, Molgó J, Distelhorst CW, Missiaen L, Mikoshiba K, Parys JB, De Smedt H, Bultynck G.

Cell Death Dis. 2013 May 16;4:e632. doi: 10.1038/cddis.2013.140.


mTOR-Controlled Autophagy Requires Intracellular Ca(2+) Signaling.

Decuypere JP, Kindt D, Luyten T, Welkenhuyzen K, Missiaen L, De Smedt H, Bultynck G, Parys JB.

PLoS One. 2013;8(4):e61020. doi: 10.1371/journal.pone.0061020. Epub 2013 Apr 2.


HA14-1, but not the BH3 mimetic ABT-737, causes Ca2+ dysregulation in platelets and human cell lines.

Akl H, Vandecaetsbeek I, Monaco G, Kauskot A, Luyten T, Welkenhuyzen K, Hoylaerts M, De Smedt H, Parys JB, Bultynck G.

Haematologica. 2013 Apr;98(4):e49-51. doi: 10.3324/haematol.2012.080598. Epub 2013 Feb 12. No abstract available.


Regulation of inositol 1,4,5-trisphosphate receptors during endoplasmic reticulum stress.

Kiviluoto S, Vervliet T, Ivanova H, Decuypere JP, De Smedt H, Missiaen L, Bultynck G, Parys JB.

Biochim Biophys Acta. 2013 Jul;1833(7):1612-24. doi: 10.1016/j.bbamcr.2013.01.026. Epub 2013 Feb 1. Review.


Polycystins and cellular Ca2+ signaling.

Mekahli D, Parys JB, Bultynck G, Missiaen L, De Smedt H.

Cell Mol Life Sci. 2013 Aug;70(15):2697-712. doi: 10.1007/s00018-012-1188-x. Epub 2012 Oct 18. Review.


Profiling of the Bcl-2/Bcl-X(L)-binding sites on type 1 IP(3) receptor.

Monaco G, Beckers M, Ivanova H, Missiaen L, Parys JB, De Smedt H, Bultynck G.

Biochem Biophys Res Commun. 2012 Nov 9;428(1):31-5. doi: 10.1016/j.bbrc.2012.10.002. Epub 2012 Oct 8.


Bax inhibitor-1 is a novel IP₃ receptor-interacting and -sensitizing protein.

Kiviluoto S, Schneider L, Luyten T, Vervliet T, Missiaen L, De Smedt H, Parys JB, Methner A, Bultynck G.

Cell Death Dis. 2012 Aug 9;3:e367. doi: 10.1038/cddis.2012.103. No abstract available.


Polycystin-1 and polycystin-2 are both required to amplify inositol-trisphosphate-induced Ca2+ release.

Mekahli D, Sammels E, Luyten T, Welkenhuyzen K, van den Heuvel LP, Levtchenko EN, Gijsbers R, Bultynck G, Parys JB, De Smedt H, Missiaen L.

Cell Calcium. 2012 Jun;51(6):452-8. doi: 10.1016/j.ceca.2012.03.002. Epub 2012 Mar 27.


Inositol 1,4,5-trisphosphate and its receptors.

Parys JB, De Smedt H.

Adv Exp Med Biol. 2012;740:255-79. doi: 10.1007/978-94-007-2888-2_11. Review.


The C terminus of Bax inhibitor-1 forms a Ca2+-permeable channel pore.

Bultynck G, Kiviluoto S, Henke N, Ivanova H, Schneider L, Rybalchenko V, Luyten T, Nuyts K, De Borggraeve W, Bezprozvanny I, Parys JB, De Smedt H, Missiaen L, Methner A.

J Biol Chem. 2012 Jan 20;287(4):2544-57. doi: 10.1074/jbc.M111.275354. Epub 2011 Nov 28.


Ins(1,4,5)P3 receptor-mediated Ca2+ signaling and autophagy induction are interrelated.

Decuypere JP, Welkenhuyzen K, Luyten T, Ponsaerts R, Dewaele M, Molgó J, Agostinis P, Missiaen L, De Smedt H, Parys JB, Bultynck G.

Autophagy. 2011 Dec;7(12):1472-89.


F508del-CFTR increases intracellular Ca(2+) signaling that causes enhanced calcium-dependent Cl(-) conductance in cystic fibrosis.

Martins JR, Kongsuphol P, Sammels E, Dahimène S, Aldehni F, Clarke LA, Schreiber R, de Smedt H, Amaral MD, Kunzelmann K.

Biochim Biophys Acta. 2011 Nov;1812(11):1385-92. doi: 10.1016/j.bbadis.2011.08.008. Epub 2011 Aug 30.


Selective regulation of IP3-receptor-mediated Ca2+ signaling and apoptosis by the BH4 domain of Bcl-2 versus Bcl-Xl.

Monaco G, Decrock E, Akl H, Ponsaerts R, Vervliet T, Luyten T, De Maeyer M, Missiaen L, Distelhorst CW, De Smedt H, Parys JB, Leybaert L, Bultynck G.

Cell Death Differ. 2012 Feb;19(2):295-309. doi: 10.1038/cdd.2011.97. Epub 2011 Aug 5.


STIM1 as a key regulator for Ca2+ homeostasis in skeletal-muscle development and function.

Kiviluoto S, Decuypere JP, De Smedt H, Missiaen L, Parys JB, Bultynck G.

Skelet Muscle. 2011 Apr 4;1(1):16. doi: 10.1186/2044-5040-1-16.


Ca(2+) signaling mechanisms of cell survival and cell death: an introduction.

De Smedt H, Verkhratsky A, Muallem S.

Cell Calcium. 2011 Sep;50(3):207-10. doi: 10.1016/j.ceca.2011.06.004. Epub 2011 Jul 7. No abstract available.


Endoplasmic-reticulum calcium depletion and disease.

Mekahli D, Bultynck G, Parys JB, De Smedt H, Missiaen L.

Cold Spring Harb Perspect Biol. 2011 Jun 1;3(6). pii: a004317. doi: 10.1101/cshperspect.a004317. Review.


IP(3) Receptors, Mitochondria, and Ca Signaling: Implications for Aging.

Decuypere JP, Monaco G, Missiaen L, De Smedt H, Parys JB, Bultynck G.

J Aging Res. 2011 Mar 8;2011:920178. doi: 10.4061/2011/920178.


Unraveling the role of polycystin-2/inositol 1,4,5-trisphosphate receptor interaction in Ca signaling.

Sammels E, Devogelaere B, Mekahli D, Bultynck G, Missiaen L, Parys JB, De Smedt H.

Commun Integr Biol. 2010 Nov;3(6):530-2. doi: 10.4161/cib.3.6.12751. Epub 2010 Nov 1.


Induction of Ca²+-driven apoptosis in chronic lymphocytic leukemia cells by peptide-mediated disruption of Bcl-2-IP3 receptor interaction.

Zhong F, Harr MW, Bultynck G, Monaco G, Parys JB, De Smedt H, Rong YP, Molitoris JK, Lam M, Ryder C, Matsuyama S, Distelhorst CW.

Blood. 2011 Mar 10;117(10):2924-34. doi: 10.1182/blood-2010-09-307405. Epub 2010 Dec 30.


The IP(3) receptor-mitochondria connection in apoptosis and autophagy.

Decuypere JP, Monaco G, Bultynck G, Missiaen L, De Smedt H, Parys JB.

Biochim Biophys Acta. 2011 May;1813(5):1003-13. doi: 10.1016/j.bbamcr.2010.11.023. Epub 2010 Dec 10. Review.


STIM1, but not STIM2, is required for proper agonist-induced Ca2+ signaling.

Decuypere JP, Monaco G, Kiviluoto S, Oh-hora M, Luyten T, De Smedt H, Parys JB, Missiaen L, Bultynck G.

Cell Calcium. 2010 Aug-Sep;48(2-3):161-7. doi: 10.1016/j.ceca.2010.08.003.


Pannexin channels in ATP release and beyond: an unexpected rendezvous at the endoplasmic reticulum.

D'hondt C, Ponsaerts R, De Smedt H, Vinken M, De Vuyst E, De Bock M, Wang N, Rogiers V, Leybaert L, Himpens B, Bultynck G.

Cell Signal. 2011 Feb;23(2):305-16. doi: 10.1016/j.cellsig.2010.07.018. Epub 2010 Aug 3. Review.


Intramolecular loop/tail interactions are essential for connexin 43-hemichannel activity.

Ponsaerts R, De Vuyst E, Retamal M, D'hondt C, Vermeire D, Wang N, De Smedt H, Zimmermann P, Himpens B, Vereecke J, Leybaert L, Bultynck G.

FASEB J. 2010 Nov;24(11):4378-95. doi: 10.1096/fj.09-153007. Epub 2010 Jul 15.


Polycystin-2 activation by inositol 1,4,5-trisphosphate-induced Ca2+ release requires its direct association with the inositol 1,4,5-trisphosphate receptor in a signaling microdomain.

Sammels E, Devogelaere B, Mekahli D, Bultynck G, Missiaen L, Parys JB, Cai Y, Somlo S, De Smedt H.

J Biol Chem. 2010 Jun 11;285(24):18794-805. doi: 10.1074/jbc.M109.090662. Epub 2010 Apr 7.


Intracellular Ca2+ storage in health and disease: a dynamic equilibrium.

Sammels E, Parys JB, Missiaen L, De Smedt H, Bultynck G.

Cell Calcium. 2010 Apr;47(4):297-314. doi: 10.1016/j.ceca.2010.02.001. Epub 2010 Mar 1. Review.


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