共查询到20条相似文献,搜索用时 15 毫秒
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Srinivasan S Bolick DT Hatley ME Natarajan R Reilly KB Yeh M Chrestensen C Sturgill TW Hedrick CC 《The Journal of biological chemistry》2004,279(30):31930-31936
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p38 mitogen-activated protein kinase plays an inhibitory role in hepatic lipogenesis 总被引:1,自引:0,他引:1
Xiong Y Collins QF An J Lupo E Liu HY Liu D Robidoux J Liu Z Cao W 《The Journal of biological chemistry》2007,282(7):4975-4982
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K Kotani W Ogawa Y Hino T Kitamura H Ueno W Sano C Sutherland D K Granner M Kasuga 《The Journal of biological chemistry》1999,274(30):21305-21312
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A role for both Ets and C/EBP transcription factors and mRNA stabilization in the MAPK-dependent increase in p21 (Cip-1/WAF1/mda6) protein levels in primary hepatocytes 下载免费PDF全文
Park JS Qiao L Gilfor D Yang MY Hylemon PB Benz C Darlington G Firestone G Fisher PB Dent P 《Molecular biology of the cell》2000,11(9):2915-2932
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Ikeda H Omoteyama K Yoshida K Nishi S Sakai M 《The Journal of biological chemistry》2006,281(10):6734-6741
The rat placental glutathione S-transferase (GST-P), an isozyme of glutathione S-transferase, is not expressed in normal liver but is highly induced at an early stage of chemical hepatocarcinogenesis and in hepatomas. Recently, we reported that the NF-E2 p45-related factor 2 (Nrf2)/MafK heterodimer binds to GST-P enhancer 1 (GPE1), a strong enhancer of the GST-P gene, and activates this gene in preneoplastic lesions and hepatomas. In addition to the positive regulation during hepatocarcinogenesis, negative regulatory mechanisms might work to repress GST-P in normal liver, but this remains to be clarified. In this work, we identify the CCAAT enhancer-binding protein alpha (C/EBPalpha) as a negative regulator that binds to GPE1 and suppresses GST-P expression in normal liver. C/EBPalpha binds to part of the GPE1 sequence, and the binding of Nrf2/MafK and C/EBPalpha to GPE1 is mutually exclusive. In a transient-transfection analysis, C/EBPalpha activated GPE1 in F9 embryonal carcinoma cells but strongly inhibited GPE1 activity in hepatoma cells. The expression of C/EBPalpha was specifically suppressed in GST-P-positive preneoplastic foci in the livers of carcinogentreated rats. A chromatin immunoprecipitation analysis showed that C/EBPalpha bound to GPE1 in the normal liver in vivo but did not bind in preneoplastic hepatocytes. Introduction of the C/EBPalpha gene fused with the estrogen receptor ligand-binding domain into hepatoma cells, and subsequent activation by beta-estradiol led to the suppression of endogenous GST-P expression. These results indicate that C/EBPalpha is a negative regulator of GST-P gene expression in normal liver. 相似文献