論文 - 詳細
RRC ID | 63512 |
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著者 | Fujita H, Aratani S, Fujii R, Yamano Y, Yagishita N, Araya N, Izumi T, Azakami K, Hasegawa D, Nishioka K, Nakajima T. |
タイトル | Mitochondrial ubiquitin ligase activator of NF-κB regulates NF-κB signaling in cells subjected to ER stress. |
ジャーナル | Int J Mol Med |
Abstract |
The nuclear factor-κB (NF-κB) transcription factor family members control various biological processes, such as apoptosis and proliferation. The endoplasmic reticulum (ER) has emerged as a major site of cellular homeostasis regulation. The accumulation of misfolded protein in the ER causes stress and ER stress-induced NF-κB activation to protect cells from apoptosis. In this study, we found a putative ER stress-response element (ERSE) on the promoter of mitochondrial ubiquitin ligase activator of NF-κB (MULAN), and that MULAN expression was upregulated by ER stress. MULAN specifically activated NF-κB dependent gene expression in an E3 ligase activity-dependent manner. The ectopic expression of MULAN induced the nuclear translocation of endogenous p65 and the degradation of IκB. Binding assay revealed that MULAN was associated with transforming growth factor β-activated kinase (TAK1). The knockdown of MULAN using siRNA inhibited the activation of NF-κB in the cells subjected to ER stress. The findings of our study indicate that MULAN is an E3 ligase that regulates NF-κB activation to protect cells from ER stress-induced apoptosis. |
巻・号 | 37(6) |
ページ | 1611-8 |
公開日 | 2016-6-1 |
DOI | 10.3892/ijmm.2016.2566 |
PMID | 27082251 |
MeSH | Apoptosis / drug effects Base Sequence Endoplasmic Reticulum / drug effects Endoplasmic Reticulum / metabolism Endoplasmic Reticulum Stress / drug effects Endoplasmic Reticulum Stress / genetics* Gene Expression Regulation HEK293 Cells HeLa Cells Humans I-kappa B Kinase / genetics I-kappa B Kinase / metabolism MAP Kinase Kinase Kinases / genetics MAP Kinase Kinase Kinases / metabolism Mitochondria / drug effects Mitochondria / metabolism* Plasmids / chemistry Plasmids / metabolism Proteolysis / drug effects RNA, Small Interfering / genetics RNA, Small Interfering / metabolism Signal Transduction* Transcription Factor RelA / antagonists & inhibitors Transcription Factor RelA / genetics* Transcription Factor RelA / metabolism Transfection Tunicamycin / pharmacology Ubiquitin-Protein Ligases / antagonists & inhibitors Ubiquitin-Protein Ligases / genetics* Ubiquitin-Protein Ligases / metabolism |
IF | 3.098 |
リソース情報 | |
ヒト・動物細胞 | HeLa 293(RCB1637) |