Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10750219 | Biochemical and Biophysical Research Communications | 2015 | 6 Pages |
Abstract
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, ÎGCN5, 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 ÎGCN5. These data revealed that GCN5 is involved in regulation of prolonged ER stress-induced apoptosis through controlling Bcl-2 gene expression.
Keywords
Bcl-2IRE1inositol-requiring protein 1B-cell lymphoma extra-largeGCN5XBP-1Bcl-xLGRP78C/EBP-homologous proteinER stressBaxCHOPX-box binding protein-1sagaApoptosisendoplasmic reticulumactivating transcription factor 4activating transcription factor 6B-cell lymphoma 2Gene targetingglucose-regulated protein 78protein kinase RNA-like ER kinasePERK
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Authors
Hidehiko Kikuchi, Futoshi Kuribayashi, Hitomi Mimuro, Shinobu Imajoh-Ohmi, Masami Nakayama, Yasunari Takami, Hideki Nishitoh, Tatsuo Nakayama,