LAP (NF-IL-6), A TISSUE-SPECIFIC TRANSCRIPTIONAL ACTIVATOR, IS AN INHIBITOR OF HEPATOMA-CELL PROLIFERATION
LAP (NF-IL-6), A TISSUE-SPECIFIC TRANSCRIPTIONAL ACTIVATOR, IS AN INHIBITOR OF HEPATOMA-CELL PROLIFERATION
复制标题
DOI：
10.1002/j.1460-2075.1994.tb06328.x
复制
发表时间：
1994-02-15
期刊：
影响因子：
11.4
通讯作者：
CHOJKIER, M
中科院分区：
文献类型：
--
作者：
BUCK, M;TURLER, H;CHOJKIER, M
在出生后肝脏发育期间，LAP（NF-IL-6、C/EBP β）表达和肝细胞增殖是相互排斥的。除了反式激活肝脏特异性基因，在肝癌细胞中，除了C/EBP α，在G（1）/S边界之前阻止细胞周期。LIP是一种肝脏抑制蛋白，它是由缺失了TGF-mRNA激活结构域的TGF-mRNA翻译而来的，它不仅不能有效地阻断肝癌细胞的增殖，而且还能拮抗TGF-mRNA对细胞周期的影响。缺失分析表明，LIP的这种作用只需要DNA结合和亮氨酸拉链结构域。此外，我们发现，β-二聚化和激活结构域的完整性是必不可少的，由β-二聚体诱导的细胞增殖的逮捕。因此，肝细胞分化和其特征性的静止状态可能是调制的β/LIP的比例。
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 G(1)/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.