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叶酸受体 alpha 的核定位:作为转录因子的新作用。

Nuclear localization of folate receptor alpha: a new role as a transcription factor.

机构信息

Department of Pediatric Neurosurgery, Ann and Robert H Lurie Children's Hospital of Chicago Research Center and Northwestern University Feinberg School of Medicine, Chicago, IL 60614, USA.

出版信息

Sci Rep. 2012;2:980. doi: 10.1038/srep00980. Epub 2012 Dec 14.

DOI:10.1038/srep00980
PMID:23243496
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3522071/
Abstract

Folic acid (FA) has traditionally been associated with prevention of neural tube defects; more recent work suggests that it may also be involved in in the prevention of adult onset diseases. As the role of FA in human health and disease expands, it also becomes more critical to understand the mechanisms behind FA action. In this work we examined the hypothesis that folate receptor alpha (FRα) acts as a transcription factor. FRα is a GPI-anchored protein and a component of the caveolae fraction. The work described here shows that FRα translocates to the nucleus, where it binds to cis-regulatory elements at promoter regions of Fgfr4 and Hes1, and regulates their expression. The FRα recognition domain mapped to AT rich regions on the promoters. Until this time FRα has only been considered as a folate transporter, these studies describe a novel role for FRα as a transcription factor.

摘要

叶酸(FA)传统上与神经管缺陷的预防有关;最近的研究表明,它也可能参与成人发病疾病的预防。随着 FA 在人类健康和疾病中的作用不断扩大,了解 FA 作用的机制也变得更加关键。在这项工作中,我们检验了叶酸受体 alpha(FRα)作为转录因子的假说。FRα 是一种 GPI 锚定蛋白,也是 caveolae 部分的组成部分。这里描述的工作表明,FRα 易位到细胞核,在那里它与 Fgfr4 和 Hes1 启动子区域的顺式调节元件结合,并调节它们的表达。FRα 识别结构域映射到启动子上的富含 AT 的区域。到目前为止,FRα 仅被认为是叶酸转运体,这些研究描述了 FRα 作为转录因子的新作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99b2/3522071/590e4620578f/srep00980-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99b2/3522071/951a1bd48069/srep00980-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99b2/3522071/6987372413ac/srep00980-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99b2/3522071/90a9598835b3/srep00980-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99b2/3522071/590e4620578f/srep00980-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99b2/3522071/951a1bd48069/srep00980-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99b2/3522071/6987372413ac/srep00980-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99b2/3522071/90a9598835b3/srep00980-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99b2/3522071/590e4620578f/srep00980-f4.jpg

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Nuclear functions and subcellular trafficking mechanisms of the epidermal growth factor receptor family.
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