IMR Press / FBL / Volume 12 / Issue 12 / DOI: 10.2741/2421

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Role of Bcl-2 family members on apoptosis: what we have learned from knock-out mice
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1 Apoptosis Signalling Group, Unitat de Biologia Cel.lular i Molecular. Institut Municipal d’Investigacio Medica (IMIM),Parc de Recerca Biomedica de Barcelona (PRBB) Aiguader, 88 08003 Barcelona, Spain
Academic Editor:Vicente Andres
Front. Biosci. (Landmark Ed) 2007, 12(12), 4722–4730; https://doi.org/10.2741/2421
Published: 1 May 2007
Abstract

B-cell lymphoma-2 (Bcl-2) family members have been demonstrated to play a crucial role in the regulation of apoptosis as mediators in between the apical stimuli sensing steps and the executory mechanisms of apoptosis. Deregulation of their role may subvert the homeostasis of a given tissue and collaborate in the genesis of a myriad of diseases characterised by exacerbated or insufficient apoptosis, including diseases such as neurodegenerative diseases or cancer. Structural studies have defined homology regions shared by the members of the family that are responsible of the network of interactions established amongst the members of the family. These proteins usually form heterodimers between the so called antiapoptotic multidomain members and the proapoptotic BH3-only proteins. As a consequence, mitochondrial apoptogenic proteins are released to the cytoplasm and the apoptotic signal proceeds towards the final, execution phase of the apoptotic process. The high complexity of the family (more than 20 members have been isolated) makes the study of individual proteins difficult. Genetic approaches have revealed a high degree of redundancy in the family. Only a few proteins belonging to the antiapoptotic group have been proven to be essential for correct embryonic development. Genetic inactivation in mice shows a dramatic phenotype characterised by massive cell death in multiple tissues during embryogenesis, which leads from very early up to perinatal death. This genetic evidence proves the importance of the members of the family for the regulation of apoptosis in order to achieve the proper development and homeostasis of tissues and organs.

Keywords
Apoptosis
Cell death
Knockout
Redundancy
Signalling
Bcl-2
Review
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