Lack of GCN5 remarkably enhances the resistance against prolonged endoplasmic reticulum stress-induced apoptosis through up-regulation of Bcl-2 gene expression.

Hidehiko Kikuchi, Futoshi Kuribayashi, Hitomi Mimuro, Shinobu Imajoh-Ohmi, Masami Nakayama, Yasunari Takami, Hideki Nishitoh, Tatsuo Nakayama

Biochemical and biophysical research communications 2015 Aug 7

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The endoplasmic reticulum (ER), a complex membrane structure, has important roles in all eukaryotic cells. Catastrophe of its functions would lead to ER stress that causes various diseases such as cancer, neurodegenerative diseases, diabetes and so on. Prolonged ER stress could trigger apoptosis via activation of various signal transduction pathways. To investigate physiological roles of histone acetyltransferase GCN5 in regulation of ER stress, we analyzed responses of homozygous GCN5-deficient DT40 mutants, ΔGCN5, against ER stress. GCN5-deficiency in DT40 caused drastic resistance against apoptosis induced by pharmacological ER stress agents (thapsigargin and tunicamycin). Pharmaceutical analysis using specific Bcl-2 inhibitors showed that the drastic resistance against prolonged ER stress-induced apoptosis is, in part, due to up-regulation of Bcl-2 gene expression in ΔGCN5. These data revealed that GCN5 is involved in regulation of prolonged ER stress-induced apoptosis through controlling Bcl-2 gene expression. Copyright © 2015 Elsevier Inc. All rights reserved.

Citation

Hidehiko Kikuchi, Futoshi Kuribayashi, Hitomi Mimuro, Shinobu Imajoh-Ohmi, Masami Nakayama, Yasunari Takami, Hideki Nishitoh, Tatsuo Nakayama. Lack of GCN5 remarkably enhances the resistance against prolonged endoplasmic reticulum stress-induced apoptosis through up-regulation of Bcl-2 gene expression. Biochemical and biophysical research communications. 2015 Aug 7;463(4):870-5