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Viewing BCL2 and cell death control from an evolutionary perspective

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Abstract

The last 30 years of studying BCL2 have brought cell death research into the molecular era, and revealed its relevance to human pathophysiology. Most, if not all metazoans use an evolutionarily conserved process for cellular self destruction that is controlled and implemented by proteins related to BCL2. We propose the anti-apoptotic BCL2-like and pro-apoptotic BH3-only members of the family arose through duplication and modification of genes for the pro-apoptotic multi-BH domain family members, such as BAX and BAK1. In that way, a cell suicide process that initially evolved as a mechanism for defense against intracellular parasites was then also used in multicellular organisms for morphogenesis and to maintain the correct number of cells in adults by balancing cell production by mitosis.

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Acknowledgements

We thank all of our current and past colleagues, and support from the Australian National Health and Medical Research Council (Program Grant 1016701 to both DLV and AS and Fellowships 1020136 to DLV and 1020363 to AS), the Leukemia and Lymphoma Society of America (LLS SCOR 7001-13 to both DLV and AS), the Cancer Council of Victoria (1052309), as well as operational infrastructure grants through the Australian Government Independent Research Institute Infrastructure Support Scheme (9000220) and the Victorian State Government Operational Infrastructure Support Program.

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  1. The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia

    Andreas Strasser & David L Vaux

  2. Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia

    Andreas Strasser & David L Vaux

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  1. Andreas Strasser
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  2. David L Vaux
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Correspondence to Andreas Strasser or David L Vaux.

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Strasser, A., Vaux, D. Viewing BCL2 and cell death control from an evolutionary perspective. Cell Death Differ 25, 13–20 (2018). https://doi.org/10.1038/cdd.2017.145

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