title: Bcl-2 regulation of the inositol 1,4,5-trisphosphate receptor and calcium signaling in normal and malignant lymphocytes: potential new target for cancer treatment.
abstract: The anti-apoptotic protein Bcl-2 is a versatile regulator of cell survival. Its interactions with its own pro-apoptotic family members are widely recognized for their role in promoting the survival of cancer cells. These interactions are thus being targeted for cancer treatment. Less widely recognized is the interaction of Bcl-2 with the inositol 1,4,5-trisphosphate receptor (InsP3R), an InsP3-gated Ca(2+) channel located on the endoplasmic reticulum. The nature of this interaction, the mechanism by which it controls Ca(2+) release from the ER, its role in T-cell development and survival, and the possibility of targeting it as a novel cancer treatment strategy are summarized in this review. This article is part of a Special Issue entitled: Calcium signaling in health and disease. Guest Editors: Geert Bultynck, Jacques Haiech, Claus W. Heizmann, Joachim Krebs, and Marc Moreau.
authors.affiliation: Division of Hematology/Oncology, Case Western Reserve University School of Medicine, Case Comprehensive Cancer Center, University Hospitals Case Medical Center, USA; MetroHealth Medical Center, USA. Electronic address: e.f.greenberg@gmail.com.
authors.forename: Edward F
authors.initials: EF
authors.lastname: Greenberg
authors.affiliation: Division of Hematology/Oncology, Case Western Reserve University School of Medicine, Case Comprehensive Cancer Center, University Hospitals Case Medical Center, USA. Electronic address: arl18@case.edu.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Lavik
authors.affiliation: Division of Hematology/Oncology, Case Western Reserve University School of Medicine, Case Comprehensive Cancer Center, University Hospitals Case Medical Center, USA. Electronic address: cwd@case.edu.
authors.forename: Clark W
authors.initials: CW
authors.lastname: Distelhorst
mesh_terms: D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002470:Cell Survival; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000378:metabolism*; D015640:Ion Channel Gating; D017136:Ion Transport; D008214:Lymphocytes / Q000378:metabolism* / Q000473:pathology; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D019253:Proto-Oncogene Proteins c-bcl-2; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium
keywords: Apoptosis; Bcl-2; Cancer; Chronic lymphocytic leukemia; Inositol 1,4,5-trisphosphate receptor; Lymphocyte