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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
来源:
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.
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页码:335 / 346
页数:12
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