A novel protein overexpressed in hepatoma accelerates export of NF-κB from the nucleus and inhibits p53-dependent apoptosis

被引:66
作者
Higashitsuji, H
Higashitsuji, H
Nagao, T
Nonoguchi, K
Fujii, S
Itoh, K
Fujita, J
机构
[1] Kyoto Univ, Fac Med, Dept Clin Mol Biol, Sakyo Ku, Kyoto 6068507, Japan
[2] Kyoto Univ, Fac Med, Dept Gynecol & Obstet, Sakyo Ku, Kyoto 6068507, Japan
关键词
D O I
10.1016/S1535-6108(02)00152-6
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
NF-kappaB is a transcription factor that can protect from or contribute to apoptosis. Here we report identification of HSCO that binds to NF-kappaB and inhibits apoptosis. HSCO mRNA was overexpressed in 20 of 30 hepatocellular carcinomas analyzed. Overexpression of HSCO inhibited caspase 9 activation and apoptosis induced by DNA damaging agents, while it augmented apoptosis induced by TNFalpha. Like IkappaBalpha, HSCO inhibited NF-kappaB activity and abrogated p53-induced apoptosis. However, the underlying mechanism was different. HSCO is a nuclear-cytoplasmic shuttling protein, bound to ReIA NF-kappaB, and HSCO sequestered it in the cytoplasm by accelerating its export from the nucleus. These results suggest that overexpression of HSCO suppresses p53-induced apoptosis by preventing nuclear localization of NF-kappaB during signaling and thus contributes to hepatocarcinogenesis.
引用
收藏
页码:335 / 346
页数:12
相关论文
共 43 条
[41]   Identification of a novel inhibitor of nuclear factor-κB RelA-associated inhibitor [J].
Yang, JP ;
Hori, M ;
Sanda, T ;
Okamoto, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (22) :15662-15670
[42]   c-Myc sensitizes cells to tumor necrosis factor-mediated apoptosis by inhibiting nuclear factor κB transactivation [J].
You, ZB ;
Madrid, LV ;
Saims, D ;
Sedivy, J ;
Wang, CY .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (39) :36671-36677
[43]   Arabidopsis glyoxalase II contains a zinc/iron binuclear metal center that is essential for substrate binding and catalysis [J].
Zang, TM ;
Hollman, DA ;
Crawford, PA ;
Crowder, MW ;
Makaroff, CA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (07) :4788-4795