Journal article
Epigenetic control of mitochondrial cell death through PACS1-mediated regulation of BAX/BAK oligomerization
D Brasacchio, AE Alsop, T Noori, M Lufti, S Iyer, KJ Simpson, PI Bird, RM Kluck, RW Johnstone, JA Trapani
Cell Death and Differentiation | NATURE PUBLISHING GROUP | Published : 2017
DOI: 10.1038/cdd.2016.119
Abstract
PCAF and ADA3 associate within the same macromolecular complexes to control the transcription of many genes, including some that regulate apoptosis. Here we show that PCAF and ADA3 regulate the expression of PACS1, whose protein product is a key component of the machinery that sorts proteins among the trans-Golgi network and the endosomal compartment. We describe a novel role for PACS1 as a regulator of the intrinsic pathway of apoptosis and mitochondrial outer membrane permeabilization. Cells with decreased PACS1 expression were refractory to cell death mediated by a variety of stimuli that operate through the mitochondrial pathway, including human granzyme B, staurosporine, ultraviolet rad..
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Funding Acknowledgements
This study was supported by Program, Fellowship and Project grant support from the National Health and Medical Research Council (NHMRC) of Australia and the Cancer Council Victoria, Australia. We thank the Australian Cancer Research Foundation for supporting the Victorian Centre for Functional Genomics and the Australian Government's Education Investment Fund Super Science Initiative support of the Australian Phenomics Network.