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肝细胞核因子4α（NF-IL-6）是一种组织特异性转录激活因子，也是肝癌细胞增殖的抑制剂。

LAP (NF-IL-6), a tissue-specific transcriptional activator, is an inhibitor of hepatoma cell proliferation.

作者信息

Buck M, Turler H, Chojkier M

机构信息

Department of Medicine, Veterans' Affairs Medical Center, San Diego, CA.

出版信息

EMBO J. 1994 Feb 15;13(4):851-60. doi: 10.1002/j.1460-2075.1994.tb06328.x.

DOI:10.1002/j.1460-2075.1994.tb06328.x
PMID:7906646
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC394884/
Abstract

During postnatal liver development, LAP (NF-IL-6, C/EBP beta) expression and hepatocyte proliferation are mutually exclusive. In addition to transactivating liver-specific genes, LAP, but not C/EBP alpha, arrests the cell cycle before the G1/S boundary in hepatoma cells. LIP, a liver-inhibitory protein, which is translated from LAP mRNA lacking the activation domain of LAP, is not only ineffective in blocking hepatoma cell proliferation but also antagonizes the effect of LAP on the cell cycle. Deletion analysis indicated that this effect of LIP required only the DNA-binding and leucine zipper domains. In addition we found that integrity of the LAP dimerization and activation domains is indispensable for the arrest of cell proliferation induced by LAP. Thus, hepatocyte differentiation and its characteristic quiescent state may be modulated by the LAP/LIP ratio.

摘要

在出生后肝脏发育过程中，LAP（NF-IL-6，C/EBPβ）的表达与肝细胞增殖相互排斥。除了反式激活肝脏特异性基因外，LAP而非C/EBPα可在肝癌细胞的G1/S边界之前使细胞周期停滞。LIP是一种肝脏抑制蛋白，由缺乏LAP激活结构域的LAP mRNA翻译而来，它不仅无法有效阻断肝癌细胞增殖，还会拮抗LAP对细胞周期的作用。缺失分析表明，LIP的这种作用仅需要DNA结合域和亮氨酸拉链域。此外，我们发现LAP二聚化结构域和激活结构域的完整性对于LAP诱导的细胞增殖停滞是不可或缺的。因此，肝细胞分化及其特征性静止状态可能受LAP/LIP比例的调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b74/394884/ea6b1761ba1f/emboj00052-0128-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b74/394884/4ddde5df0275/emboj00052-0124-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b74/394884/6c6400900906/emboj00052-0125-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b74/394884/08a32ca31e8c/emboj00052-0125-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b74/394884/57ad3ee32fb4/emboj00052-0126-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b74/394884/ea6b1761ba1f/emboj00052-0128-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b74/394884/4ddde5df0275/emboj00052-0124-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b74/394884/6c6400900906/emboj00052-0125-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b74/394884/08a32ca31e8c/emboj00052-0125-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b74/394884/57ad3ee32fb4/emboj00052-0126-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b74/394884/ea6b1761ba1f/emboj00052-0128-a.jpg

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1
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Cancer Res. 1962 Aug;22:842-9.
2
Transactivation by NF-IL6/LAP is enhanced by phosphorylation of its activation domain.NF-IL6/LAP的反式激活作用通过其激活结构域的磷酸化得以增强。
Nature. 1993 Aug 5;364(6437):544-7. doi: 10.1038/364544a0.
3
A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples.
转录因子可变剪接异构体在肝细胞癌中的异常表达。
World J Hepatol. 2018 Oct 27;10(10):645-661. doi: 10.4254/wjh.v10.i10.645.
4
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Cell Death Dis. 2018 Oct 3;9(10):1023. doi: 10.1038/s41419-018-1072-1.
5
Liver-enriched activator protein 1 as an isoform of CCAAT/enhancer-binding protein beta suppresses stem cell features of hepatocellular carcinoma.富含肝脏的激活蛋白1作为CCAAT/增强子结合蛋白β的一种同工型，可抑制肝细胞癌的干细胞特征。
Cancer Manag Res. 2018 Apr 26;10:873-885. doi: 10.2147/CMAR.S160172. eCollection 2018.
6
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7
Conjunction of potential G-quadruplex and adjacent cis-elements in the 5' UTR of hepatocyte nuclear factor 4-alpha strongly inhibit protein expression.肝细胞核因子 4-α 5'UTR 中潜在 G-四联体和顺式元件的连接强烈抑制蛋白表达。
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8
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10
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4
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5
Transcriptional control of the murine albumin/alpha-fetoprotein locus during development.发育过程中小鼠白蛋白/甲胎蛋白基因座的转录调控
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6
The interplay of DNA-binding proteins on the promoter of the mouse albumin gene.DNA结合蛋白在小鼠白蛋白基因启动子上的相互作用。
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7
The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins.亮氨酸拉链：一类新型DNA结合蛋白共有的一种假设结构。
Science. 1988 Jun 24;240(4860):1759-64. doi: 10.1126/science.3289117.
8
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Genes Dev. 1987 Dec;1(10):1172-82. doi: 10.1101/gad.1.10.1172.
9
Existence of two populations of cyclin/proliferating cell nuclear antigen during the cell cycle: association with DNA replication sites.细胞周期中细胞周期蛋白/增殖细胞核抗原的两种群体的存在：与DNA复制位点的关联。
J Cell Biol. 1987 Oct;105(4):1549-54. doi: 10.1083/jcb.105.4.1549.
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