The forkhead transcription factor foxo1 bridges the JNK pathway and the transcription factor PDX-1 through its intracellular translocation

被引:225
作者
Kawamori, D [1 ]
Kaneto, H [1 ]
Nakatani, Y [1 ]
Matsuoka, T [1 ]
Matsuhisa, M [1 ]
Hori, M [1 ]
Yamasaki, Y [1 ]
机构
[1] Osaka Univ, Grad Sch Med, Dept Internal Med & Therapeut A8, Suita, Osaka 5650871, Japan
关键词
D O I
10.1074/jbc.M508510200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
It has been shown that oxidative stress and activation of the c-Jun N-terminal kinase (JNK) pathway induce the nucleocytoplasmic translocation of the pancreatic transcription factor PDX-1, which leads to pancreatic beta-cell dysfunction. In this study, we have shown that the forkhead transcription factor Foxo1/FKHR plays a role as a mediator between the JNK pathway and PDX-1. Under oxidative stress conditions, Foxo1 changed its intracellular localization from the cytoplasm to the nucleus in the pancreatic beta-cell line HIT-T15. The overexpression of JNK also induced the nuclear localization of Foxo1, but in contrast, suppression of JNK reduced the oxidative stress-induced nuclear localization of Foxo1, suggesting the involvement of the JNK pathway in Foxo1 translocation. In addition, oxidative stress or activation of the JNK pathway decreased the activity of Akt in HIT cells, leading to the decreased phosphorylation of Foxo1 following nuclear localization. Furthermore, adenovirus-mediated Foxo1 overexpression reduced the nuclear expression of PDX-1, whereas repression of Foxo1 by Foxo1-specific small interfering RNA retained the nuclear expression of PDX-1 under oxidative stress conditions. Taken together, Foxo1 is involved in the nucleocytoplasmic translocation of PDX-1 by oxidative stress and the JNK pathway.
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页码:1091 / 1098
页数:8
相关论文
共 59 条
[1]   FoxOs at the crossroads of cellular metabolism, differentiation, and transformation [J].
Accili, D ;
Arden, KC .
CELL, 2004, 117 (04) :421-426
[2]   The c-Jun NH2-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser307 [J].
Aguirre, V ;
Uchida, T ;
Yenush, L ;
Davis, R ;
White, MF .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (12) :9047-9054
[3]   Role of translocation in the activation and function of protein kinase B [J].
Andjelkovic, M ;
Alessi, DR ;
Meier, R ;
Fernandez, A ;
Lamb, NJC ;
Frech, M ;
Cron, P ;
Cohen, P ;
Lucocq, JM ;
Hemmings, BA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (50) :31515-31524
[4]  
[Anonymous], BIOCH BIOPHYS ACTA
[5]   Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1 [J].
Biggs, WH ;
Meisenhelder, J ;
Hunter, T ;
Cavenee, WK ;
Arden, KC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (13) :7421-7426
[6]   Biochemistry and molecular cell biology of diabetic complications [J].
Brownlee, M .
NATURE, 2001, 414 (6865) :813-820
[7]   Signal transduction by the JNK group of MAP kinases [J].
Davis, RJ .
CELL, 2000, 103 (02) :239-252
[8]   Pancreatic β-cell growth and survival in the onset of type 2 diabetes:: a role for protein kinase B in the Akt? [J].
Dickson, LM ;
Rhodes, CJ .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2004, 287 (02) :E192-E198
[9]   Transcribing pancreas [J].
Edlund, H .
DIABETES, 1998, 47 (12) :1817-1823
[10]   Phosphorylation-dependent nucleocytoplasmic shuttling of pancreatic duodenal homeobox-1 [J].
Elrick, LJ ;
Docherty, K .
DIABETES, 2001, 50 (10) :2244-2252