Mitochondrial ubiquitin ligase activator of NF-κB regulates NF-κB signaling in cells subjected to ER stress

  • Authors:
    • Hidetoshi Fujita
    • Satoko Aratani
    • Ryouji Fujii
    • Yoshihisa Yamano
    • Naoko Yagishita
    • Natsumi Araya
    • Toshihiko Izumi
    • Kazuko Azakami
    • Daisuke Hasegawa
    • Kusuki Nishioka
    • Toshihiro Nakajima
  • View Affiliations

  • Published online on: April 14, 2016     https://doi.org/10.3892/ijmm.2016.2566
  • Pages: 1611-1618
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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.
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June-2016
Volume 37 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Fujita H, Aratani S, Fujii R, Yamano Y, Yagishita N, Araya N, Izumi T, Azakami K, Hasegawa D, Nishioka K, Nishioka K, et al: Mitochondrial ubiquitin ligase activator of NF-κB regulates NF-κB signaling in cells subjected to ER stress. Int J Mol Med 37: 1611-1618, 2016.
APA
Fujita, H., Aratani, S., Fujii, R., Yamano, Y., Yagishita, N., Araya, N. ... Nakajima, T. (2016). Mitochondrial ubiquitin ligase activator of NF-κB regulates NF-κB signaling in cells subjected to ER stress. International Journal of Molecular Medicine, 37, 1611-1618. https://doi.org/10.3892/ijmm.2016.2566
MLA
Fujita, H., Aratani, S., Fujii, R., Yamano, Y., Yagishita, N., Araya, N., Izumi, T., Azakami, K., Hasegawa, D., Nishioka, K., Nakajima, T."Mitochondrial ubiquitin ligase activator of NF-κB regulates NF-κB signaling in cells subjected to ER stress". International Journal of Molecular Medicine 37.6 (2016): 1611-1618.
Chicago
Fujita, H., Aratani, S., Fujii, R., Yamano, Y., Yagishita, N., Araya, N., Izumi, T., Azakami, K., Hasegawa, D., Nishioka, K., Nakajima, T."Mitochondrial ubiquitin ligase activator of NF-κB regulates NF-κB signaling in cells subjected to ER stress". International Journal of Molecular Medicine 37, no. 6 (2016): 1611-1618. https://doi.org/10.3892/ijmm.2016.2566