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: Edward F Greenberg, Andrew R Lavik, Clark W Distelhorst
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1843 Issue 10 Pg. 2205-10 (Oct 2014) ISSN: 0006-3002 [Print] Netherlands
• PMID: 24642270 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Inositol 1,4,5-Trisphosphate Receptors
• Proto-Oncogene Proteins c-bcl-2
• Inositol 1,4,5-Trisphosphate
• Calcium

Topics

• Apoptosis
• Calcium (metabolism)
• Calcium Signaling
• Cell Survival
• Endoplasmic Reticulum (metabolism)
• Gene Expression Regulation
• Humans
• Inositol 1,4,5-Trisphosphate (metabolism)
• Inositol 1,4,5-Trisphosphate Receptors (genetics, metabolism)
• Ion Channel Gating
• Ion Transport
• Lymphocytes (metabolism, pathology)
• Neoplasms (metabolism, pathology)
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)