XIHbox 8, an endoderm-specific Xenopus homeodomain protein, is closely related to a mammalian insulin gene transcription factor.

XIHbox 8, an endoderm-specific Xenopus homeodomain protein, is closely related to a mammalian insulin gene transcription factor.
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XIHbox 8 是一种内胚层特异性爪蟾同源域蛋白,与哺乳动物胰岛素基因转录因子密切相关。

DOI:
10.1210/mend.8.6.7935494
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发表时间:
1994
影响因子:
--
通讯作者:
R. Stein
R. Stein
中科院分区:
医学2区
文献类型:
--
作者:
M. Peshavaria;L. Gamer;E. Henderson;G. Teitelman;C. Wright;R. Stein

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仅在胰岛β细胞中介导胰岛素基因表达的顺式作用序列位于核苷酸-340和-91之间的5 '侧翼区域内。我们已经在大鼠胰岛素II基因的-201/-196个碱基对处鉴定了一个进化上保守的富含A+ T的元件,该元件对于在β细胞中的有效表达是必需的。针对XIHbox 8蛋白的亲和纯化的抗体使主要的β-细胞激活因子复合物与-201/-196元件的结合超移位。XIHbox 8是爪蟾内胚层特异性同源结构域蛋白,其表达限于十二指肠和发育中的胰腺的内胚层细胞的核。针对XIHbox 8的抗体与存在于该DNA复合物中的47千道尔顿蛋白质特异性相互作用。免疫组织化学研究显示,几乎所有小鼠胰岛β细胞和胰岛α细胞和β细胞亚群的细胞核内均存在XIHbox 8样蛋白。这些结果与哺乳动物胰岛素基因在β细胞中表达所需的47千道尔顿的XIHbox 8相关同源异型蛋白的提议一致。用生长抑素转录因子-1(STF-1)(最近分离的哺乳动物XIHbox 8相关同源异型蛋白)的抗血清进行的实验表明,STF-1蛋白是非洲爪蟾XIHbox 8的哺乳动物同源物。
The cis-acting sequences that mediate insulin gene expression exclusively in pancreatic islet beta-cells are localized within the 5'-flanking region between nucleotides -340 and -91. We have identified an evolutionarily conserved, A+T-rich element at -201/-196 basepairs in the rat insulin II gene that is essential for efficient expression in beta-cells. Affinity-purified antibody to the XIHbox 8 protein super-shifted the major beta-cell-activator factor complex binding to the -201/-196 element. XIHbox 8 is a Xenopus endoderm-specific homeodomain protein whose expression is restricted to the nucleus of endodermal cells of the duodenum and developing pancreas. Antibody to XIHbox 8 specifically interacts with a 47-kilodalton protein present in this DNA complex. Immunohistochemical studies revealed XIHbox 8-like proteins within the nucleus of almost all mouse islet beta-cells and a subset of islet alpha- and beta-cells. These results are consistent with the proposal that an XIHbox 8-related homeoprotein of 47 kilodalton is required for expression of the mammalian insulin gene in beta-cells. Experiments conducted with antiserum raised to somatostatin transcription factor-1 (STF-1), a recently isolated mammalian XIHbox 8-related homeoprotein, indicate that the STF-1 protein is the mammalian homolog of Xenopus XIHbox 8.
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