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TMBIM protein family: ancestral regulators of cell death

Oncogene volume 34, pages 269–280 (2015)Cite this article

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Abstract

The control of apoptosis in mammals has been historically associated with the activity of the BCL-2 family of proteins at the mitochondria. In the past years, a novel group of cell death regulators have emerged, known as the Transmembrane BAX Inhibitor-1 Motif-containing (TMBIM) protein family. This group of proteins is composed of at least six highly conserved members expressed in mammals, with homologs in insects, fish, plants, viruses and yeast. Different studies indicate that all TMBIM family members have inhibitory activities in different setting of apoptosis. Here, we overview and integrate possible mechanisms underlying the impact of the TMBIM protein family in the regulation of cell death, which include activities at diverse subcellular compartments, including death receptor regulation, modulation of endoplasmic reticulum (ER) calcium homeostasis, ER stress signaling, autophagy, reactive oxygen species production, among other effects. The possible intersection between the BCL-2 and TMBIM family in the control of cell death is also discussed, in addition to their implication in the progression of cancer.

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Acknowledgements

This work was funded by FONDEF D11I1007, Ring Initiative ACT1109, Millennium Institute No. P09-015-F, the Alzheimeŕs Association, FONDECYT No. 1100176, FONDECYT No. 1140549, ECOS CONICYT C13S02 CONICYT Grant USA2013-0003, the Muscular Dystrophy Association, ALS Therapy Alliance (CH) and FONDECYT No. 3130365 Post-doctoral grant (DRR).

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  1. Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile

    D Rojas-Rivera & C Hetz

  2. Center for Molecular Studies of the Cell, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile

    D Rojas-Rivera & C Hetz

  3. Harvard School of Public Health, Boston, MA, USA

    C Hetz

  4. Neurounion Biomedical Foundation, Santiago, Chile

    C Hetz

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  1. D Rojas-Rivera
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Rojas-Rivera, D., Hetz, C. TMBIM protein family: ancestral regulators of cell death. Oncogene 34, 269–280 (2015). https://doi.org/10.1038/onc.2014.6

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