RRC ID 63512
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)