Differential splicing of the GHF1 primary transcript gives rise to two functionally distinct homeodomain proteins.
Differential splicing of the GHF1 primary transcript gives rise to two functionally distinct homeodomain proteins.
复制标题
GHF1 初级转录物的差异剪接产生两种功能不同的同源域蛋白。
DOI：
10.1002/j.1460-2075.1992.tb05285.x
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Karin,M
中科院分区：
文献类型：
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作者：
Theill,LE;Hattori,K;Lazzaro,D;Castrillo,JL;Karin,M
POU结构域蛋白GHF-1在三种类型的垂体细胞的生成、增殖和表型表达中起关键作用。GHF-1的部分功能是通过结合和反式激活生长激素(GH)和催乳素(PRL)基因的启动子以及GHF1基因本身的启动子来发挥作用。我们描述了GHF-1的一种自然存在的亚型，GHF-2，其中由于选择性剪接，额外的26个氨基酸被插入到蛋白质的激活域中。GHF-2保留了GHF-1的DNA结合活性，并能激活GH启动子，但失去了激活PRL和GHF1启动子的能力。这些结果表明，GHF-2可能在生长激素谱系分化过程中的差异靶基因激活中发挥作用。GHF-1和GHF-2转录本均在垂体前叶特异表达。对基因组GHF1基因的分析表明，GHF-1(和GHF-2)的大部分不同功能结构域是由不同的外显子编码的。基因片段复制和外显子改组可能有助于这种细胞类型特异的转录调控基因的进化。
The POU domain protein GHF‐1 has a critical role in generation, proliferation and phenotypic expression of three pituitary cell types. GHF‐1 functions in part by binding to and transactivating the promoters of both the growth hormone (GH) and prolactin (PRL) genes and that of the GHF1 gene itself. We describe a naturally occurring isoform of GHF‐1, GHF‐2, in which an additional 26 amino acids are inserted into the activation domain of the protein as a result of alternative splicing. GHF‐2 retains the DNA binding activity of GHF‐1 and can activate the GH promoter but has lost the ability to activate the PRL and GHF1 promoters. These results suggest that GHF‐2 may function in differential target gene activation during differentiation of the somatotrophic lineage. Both GHF‐1 and GHF‐2 transcripts are specifically expressed in the anterior pituitary. Analysis of the genomic GHF1 gene shows that most of the distinct functional domains of GHF‐1 (and GHF‐2) are encoded by separate exons. Gene segment duplication and exon shuffling may have contributed to the evolution of this cell type‐specific transcriptional regulatory gene.