title: Protect and serve: Bcl-2 proteins as guardians and rulers of cancer cell survival.
abstract: It is widely accepted that anti-apoptotic Bcl-2 family members promote cancer cell survival by binding to their pro-apoptotic counterparts, thereby preventing mitochondrial outer membrane permeabilization (MOMP) and cytotoxic caspase activation. Yet, these proteins do not only function as guardians of mitochondrial permeability, preserving it, and maintaining cell survival in the face of acute or chronic stress, they also regulate non-apoptotic functions of caspases and biological processes beyond MOMP from diverse subcellular localizations and in complex with numerous binding partners outside of the Bcl-2 family. In particular, some of the non-canonical effects and functions of Bcl-2 homologs lead to an interplay with E2F-1, NFκB, and Myc transcriptional pathways, which themselves influence cancer cell growth and survival. We thus propose that, by feedback loops that we currently have only hints of, Bcl-2 proteins may act as rulers of survival signaling, predetermining the apoptotic threshold that they also directly scaffold. This underscores the robustness of the control exerted by Bcl-2 homologs over cancer cell survival, and implies that small molecules compounds currently used in the clinic to inhibit their mitochondrial activity may be not always be fully efficient to override this control.
authors: UMR 892 INSERM/6299 CNRS/Université de Nantes; Team 8 "Cell survival and tumor escape in breast cancer"; Institut de Recherche en Santé de l'Université de Nantes; Nantes, France.
authors: Frédérique
authors: F
authors: Braun
authors: Sophie
authors: S
authors: de Carné Trécesson
authors: Joséphine
authors: J
authors: Bertin-Ciftci
authors: Philippe
authors: P
authors: Juin
mesh_terms: D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002463:Cell Membrane Permeability; D050687:E2F1 Transcription Factor / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism
chemical_list: D050687:E2F1 Transcription Factor; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D020169:Caspases
keywords: Bcl-2 family; E2F-1; Myc; NF-κB; caspase
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