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首页> 美国卫生研究院文献>Molecular Endocrinology >A Novel Role for the AAA ATPase Spastin as a HOXA10 Transcriptional Corepressor in Ishikawa Endometrial Cells
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A Novel Role for the AAA ATPase Spastin as a HOXA10 Transcriptional Corepressor in Ishikawa Endometrial Cells

机译：石川县子宫内膜细胞中AAA ATPase Spastin作为HOXA10转录共表达的新型作用。

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摘要

Homeobox A10 (HOXA10), a transcription factor required for uterine development and embryo receptivity, functions downstream of estrogen and progesterone in uterine endometrium. HOXA10 represses endometrial expression of empty spiracles homeobox 2 (EMX2), the human ortholog of Drosophila empty spiracles. The ATPases associated with various cellular activities (AAA) ATPase spastin has a well-characterized role in neurotransmitter trafficking. In this study, we characterize a novel role of spastin in transcriptional regulation. We identified spastin as a novel component of the HOXA10 transcriptional complex in Ishikawa nuclear extracts by immunoprecipitation and mass spectrophotometry. Using EMX2 as a model endometrial HOXA10 target gene, we show that the HOXA10-spastin corepressor complex bound the EMX2 promoter in chromatin immunoprecipitation assays. HOXA10 has been previously shown to repress endometrial EMX2 expression. We further observed that, although cotransfection of HOXA10 and spastin continued to repress endometrial EMX2-luciferase expression, the repression was reversed when spastin small interfering RNA was cotransfected with HOXA10. Mutations in the nuclear localization signal sequences of spastin abrogated not only its nuclear translocation but also its colocalization with HOXA10 as well as reversed EMX2-luciferase repression. Here, we describe a novel role for the AAA ATPase spastin in Ishikawa cells as a HOXA10 corepressor of EMX2. Uterine EMX2 levels are inversely related to embryo implantation rates. HOXA10 acts downstream of progesterone and has been shown to facilitate embryo implantation through regulation of endometrial EMX2 expression. Endometrial spastin, therefore, likely has a novel function downstream of estrogen and progesterone in implantation biology as a cofactor of HOXA10.
机译：Homeobox A10（HOXA10）是子宫发育和胚胎接受性所必需的转录因子，在子宫内膜中雌激素和孕激素的下游起作用。 HOXA10可以抑制果蝇空拟人的直系同源物空拟人同源盒2（EMX2）的子宫内膜表达。与各种细胞活动（AAA）ATPase spastin相关的ATPase在神经递质运输中具有很好的特征。在这项研究中，我们表征了spastin在转录调控中的新作用。我们通过免疫沉淀和质谱法将spastin鉴定为石川核提取物中HOXA10转录复合物的新型成分。使用EMX2作为模型子宫内膜HOXA10靶基因，我们证明了HOXA10-spastin的corepressor复合体在染色质免疫沉淀试验中结合了EMX2启动子。以前已显示HOXA10抑制子宫内膜EMX2表达。我们进一步观察到，尽管HOXA10和spastin的共转染继续抑制子宫内膜EMX2-荧光素酶的表达，但当spastin小干扰RNA与HOXA10共转染时，这种阻遏作用被逆转了。 Spastin的核定位信号序列中的突变不仅废除了其核易位，而且还废除了与HOXA10的共定位以及逆转的EMX2-荧光素酶阻遏作用。在这里，我们描述了石川细胞中AAA ATPase spastin作为EMX2的HOXA10核心抑制剂的新型作用。子宫EMX2水平与胚胎着床率成反比。 HOXA10在孕激素的下游起作用，并已显示可通过调节子宫内膜EMX2表达来促进胚胎植入。因此，子宫内膜spastin可能作为HOXA10的辅助因子，在植入生物学中在雌激素和孕酮的下游具有新功能。

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