The JNK pathway modulates expression and phosphorylation of 4E-BP1 in MIN6 pancreatic b-cells under oxidative stress conditions

Ryu Tominaga, Suguru Yamaguchi, Chihiro Satake, Masahiro Usui, Yasuhiro Tanji, Keiichi Kondo, Hideki Katagiri, Yoshitomo Oka, Hisamitsu Ishihara

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10 Citations (Scopus)


Stress-mediated apoptosis may play a crucial role in loss of pancreatic β-cell mass, contributing to the development of diabetes. We have recently identified that translational control involving the translational suppressor eIF4E binding protein-1 (4E-BP1) which is important for βcell survival under endoplasmic reticulum (ER) stress. The Eif4ebp1 gene, encoding 4E-BP1, is a direct target of a transcription factor activating transcription factor-4 (ATF4), a master regulator of gene expression in stress responses. In the current study, we investigated 4EBP1 expression in mouse insulinoma line 6 (MIN6) cells treated with arsenite, an inducer of oxidative stress which is another contributor of βcell loss.We found that arsenite-induced 4E-BP1 expression level was lower than that induced by thapsigargin, an ER stress inducer, although ATF4 was similarly induced by these agents. The ratio of the dephosphorylated form of 4E-BP1, which has the highest activity, to phosphorylated forms was, however, greater in MIN6 cells treated with arsenite as compared to that in thapsigargin-treated cells. Arseniteinduced 4E-BP1 mRNA and protein expressions were augmented by simultaneous treatment with a c-Jun N-terminal kinase (JNK) specific inhibitor, SP600125. The agent also suppressed the level of the dephosphrylated form of 4E-BP1 in arsenite-treated MIN6 cells. Thus, JNK activated by oxidative stress is involved in the modulation of 4E-BP1 expression and phosphorylation in MIN6 cells, which may contribute to fine tuning of translational control under stress conditions.

Original languageEnglish
Pages (from-to)387-393
Number of pages7
JournalCell Biochemistry and Function
Issue number5
Publication statusPublished - 2010 Jul


  • 4E-BP1
  • ER stress
  • JNK
  • Oxidative stress
  • Pancreatic b-cells


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