Epigenetic control of mitochondrial cell death through PACS1-mediated regulation of BAX/BAK oligomerization
Details
Publication Year 2017, Volume 24, Issue #6, Page 961-970
Journal Title
Cell Death and Differentiation
Publication Type
Journal Article
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 radiation and etoposide, but remained sensitive to TRAIL receptor ligation. The mitochondria of protected cells failed to release cytochrome c as a result of perturbed oligomerization of BAX and BAK. We conclude that PCAF and ADA3 transcriptionally regulate PACS1 and that PACS1 is a key regulator of BAX/BAK oligomerization and the intrinsic (mitochondrial) pathway to apoptosis.Cell Death and Differentiation advance online publication, 6 January 2017; doi:10.1038/cdd.2016.119.
PubMed ID
28060382
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2017-01-10 12:24:14
Last Modified: 2018-07-04 11:36:21
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