ERBB receptor feedback inhibitor 1: Identification and regulation by estrogen in chickens
ERBB receptor feedback inhibitor 1: Identification and regulation by estrogen in chickens
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DOI：
10.1016/j.ygcen.2011.11.013
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发表时间：
2012-01-01
影响因子：
2.7
通讯作者：
Song, Gwonhwa
中科院分区：
文献类型：
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作者：
Ahn, Suzie E.;Jeong, Wooyoung;Song, Gwonhwa
ERBB受体反馈抑制剂1 （ERRFI1）是一种支架接头蛋白，在表皮生长因子受体（EGFR）细胞信号级联中起关键作用，是影响许多重要生理过程的负调节因子。最近有报道称，在小鼠体内，ERRFI1是子宫内膜响应雌激素调节组织稳态的关键调节因子。但是，我们对鸡体内的ERRFI1基因和激素调控知之甚少。因此，本研究克隆了ERRFI1基因，并分析了其在雌激素处理鸡的不同胚胎阶段、不同成体器官和输卵管中的差异表达谱。鸡ERRFI1具有2848个核苷酸的开放阅读框，编码465个氨基酸的蛋白，与哺乳动物ERRFI1蛋白具有相当大的同源性（>62%的同源性）。重要的是，ERRFI1 mRNA在鸡的各种器官中大量分布。然后，我们确定DES（二乙基己烯雌酚，一种合成的非甾体雌激素）在输卵管管腔和腺上皮细胞中主要诱导ERRFI1 mRNA和蛋白。此外，我们确定了microRNAs，特别是miR-2006、miR-429和miR-1639是否通过其3'UTR影响ERRFI1的表达，并发现它并不直接靶向ERRFI1 mRNA的3'UTR。因此，转录后调控不太可能影响鸡输卵管中ERRFI1的表达。综上所述，我们的研究结果表明ERRFI1是在鸡输卵管上皮细胞中表达的一种新的雌激素刺激基因，可能在鸡早期发育过程中对输卵管的生长和分化起重要作用。(C) 2011爱思唯尔公司版权所有。
The ERBB receptor feedback inhibitor 1 (ERRFI1) is a scaffolding adaptor protein, that plays a pivotal role in the epidermal growth factor receptor (EGFR) cell signaling cascade as a negative regulator affecting many important physiological processes. It was recently reported that ERRFI1 is a critical regulator of the response of the endometrium to estrogen regulation of tissue homeostasis in mice. But, very little is known about ERRFI1 and hormonal regulation of the ERRFI1 gene in chickens. Therefore, in the present study, ERRFI1 gene was cloned and its differential expression profile analyzed at different embryonic stages, in various adult organs, and in oviducts from estrogen-treated chickens. Chicken ERRFI1 has an open-reading frame of 2848 nucleotides that encode for a protein of 465 amino acids that has considerable homology to mammalian ERRFI1 proteins (>62% identity). Importantly, ERRFI1 mRNA is abundantly distributed in various organs from chickens. We then determined that DES (diethylstilbestrol, a synthetic nonsteroidal estrogen) induced ERRFI1 mRNA and protein predominantly in luminal and glandular epithelial cells of the oviduct. Further, we determined whether microRNAs, specifically miR-2006, miR-429 and miR-1639, influence ERRFI1 expression via its 3'UTR and found that it does not directly target the 3'UTR of ERRFI1 mRNA. Therefore, it is unlikely that post-transcriptional regulation influences ERRFI1 expression in the chicken oviduct. In conclusion, our results indicate that ERRFI1 is a novel estrogen-stimulated gene expressed in epithelial cells of the chicken oviduct that likely plays an important role in oviduct growth and differentiation during early development of the chicken. (C) 2011 Elsevier Inc. All rights reserved.