Galarneau L, Paré J F, Allard D, Hamel D, Levesque L, Tugwood J D, Green S, Bélanger L
Le Centre de Recherche en Cancérologie de 1' Université Laval, L' Hôtel-Dieu de Québec, Canada.
Mol Cell Biol. 1996 Jul;16(7):3853-65. doi: 10.1128/MCB.16.7.3853.
The alpha1-fetoprotein (AFP) gene is located between the albumin and alpha-albumin genes and is activated by transcription factor FTF (fetoprotein transcription factor), presumed to transduce early developmental signals to the albumin gene cluster. We have identified FTF as an orphan nuclear receptor of the Drosophila FTZ-F1 family. FTF recognizes the DNA sequence 5'-TCAAGGTCA-3', the canonical recognition motif for FTZ-F1 receptors. cDNA sequence homologies indicate that rat FTF is the ortholog of mouse LRH-1 and Xenopus xFF1rA. Rodent FTF is encoded by a single-copy gene, related to the gene encoding steroidogenic factor 1 (SF-1). The 5.2-kb FTF transcript is translated from several in-frame initiator codons into FTF isoforms (54 to 64 kDa) which appear to bind DNA as monomers, with no need for a specific ligand, similar KdS (approximately equal 3 x 10(-10) M), and similar transcriptional effects. FTF activates the AFP promoter without the use of an amino-terminal activation domain; carboxy-terminus-truncated FTF exerts strong dominant negative effects. In the AFP promoter, FTF recruits an accessory trans-activator which imparts glucocorticoid reactivity upon the AFP gene. FTF binding sites are found in the promoters of other liver-expressed genes, some encoding liver transcription factors; FTF, liver alpha1-antitrypsin promoter factor LFB2, and HNF-3beta promoter factor UF2-H3beta are probably the same factor. FTF is also abundantly expressed in the pancreas and may exert differentiation functions in endodermal sublineages, similar to SF-1 in steroidogenic tissues. HepG2 hepatoma cells seem to express a mutated form of FTF.
甲胎蛋白（AFP）基因位于白蛋白基因和α-白蛋白基因之间，由转录因子FTF（胎蛋白转录因子）激活，推测该转录因子将早期发育信号传导至白蛋白基因簇。我们已确定FTF是果蝇FTZ-F1家族的一个孤儿核受体。FTF识别DNA序列5'-TCAAGGTCA-3'，这是FTZ-F1受体的典型识别基序。cDNA序列同源性表明，大鼠FTF是小鼠LRH-1和非洲爪蟾xFF1rA的直系同源物。啮齿动物FTF由单拷贝基因编码，与编码类固醇生成因子1（SF-1）的基因相关。5.2kb的FTF转录本从几个读框内起始密码子翻译为FTF同工型（54至64kDa），这些同工型似乎以单体形式结合DNA，无需特定配体，具有相似的解离常数（约等于3×10⁻¹⁰M）和相似的转录效应。FTF无需使用氨基末端激活域即可激活AFP启动子；羧基末端截短的FTF发挥强烈的显性负效应。在AFP启动子中，FTF招募一种辅助反式激活因子，该因子赋予AFP基因糖皮质激素反应性。在其他肝脏表达基因的启动子中发现了FTF结合位点，其中一些基因编码肝脏转录因子；FTF、肝脏α1-抗胰蛋白酶启动子因子LFB2和HNF-3β启动子因子UF2-H3β可能是同一因子。FTF在胰腺中也大量表达，可能在内胚层亚谱系中发挥分化功能，类似于类固醇生成组织中的SF-1。HepG2肝癌细胞似乎表达一种突变形式的FTF。
