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

Vanda Boshnjaku; Kyu Won Shim; Takao Tsurubuchi; Shunsuke Ichi; Elise V. Szany; Guifa Xi; Barbara Mania-Farnell; David G. McLone; Tadanori Tomita; C. Shekhar Mayanil

doi:10.1038/srep00980

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

Vanda Boshnjaku, Kyu Won Shim, Takao Tsurubuchi, Shunsuke Ichi, Elise V. Szany, Guifa Xi, Barbara Mania-Farnell, David G. McLone, Tadanori Tomita, C. Shekhar Mayanil^*

^*Corresponding author for this work

Neurological Surgery

Research output: Contribution to journal › Article › peer-review

82 Scopus citations

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.

Original language	English (US)
Article number	980
Journal	Scientific reports
Volume	2
DOIs	https://doi.org/10.1038/srep00980
State	Published - 2012

Funding

This work was supported by the State of Illinois Excellence in Academic Medicine award (C. S. M.), a Grant from the Spastic Paralysis Research Foundation of Illinois-Eastern Iowa District of Kiwanis (C. S. M. and D. G. M.), the Spina Bifida Association and CHCRC Pilot Grant award (C. S. M.). We thank Dr. R. Kageyama, Institute for Virus Research, Kyoto University Kyoto, Japan, for providing the Hes1 promoter-luciferase construct; Dr Shereen Ezzat, Departments of Medicine, Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada for providing Human FGFR4 promoter constructs; Dr Asok Antony, Indiana University Medical School, Indianapolis, IN, USA for providing the FRa expression construct in pcDNA3 and GST-FRa plasmids; and William Goossens, manager of the Microscopy and Imaging Facility at Children’s Hospital of Chicago Research Center for assistance with confocal microscopy. We thank Bio-Rad for their generous gift of Trans-Blot Turbo and the ChemiDocMP system.

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General

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/srep00980

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title = "Nuclear localization of folate receptor alpha: A new role as a transcription factor",

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.",

author = "Vanda Boshnjaku and Shim, {Kyu Won} and Takao Tsurubuchi and Shunsuke Ichi and Szany, {Elise V.} and Guifa Xi and Barbara Mania-Farnell and McLone, {David G.} and Tadanori Tomita and Mayanil, {C. Shekhar}",

note = "Funding Information: This work was supported by the State of Illinois Excellence in Academic Medicine award (C. S. M.), a Grant from the Spastic Paralysis Research Foundation of Illinois-Eastern Iowa District of Kiwanis (C. S. M. and D. G. M.), the Spina Bifida Association and CHCRC Pilot Grant award (C. S. M.). We thank Dr. R. Kageyama, Institute for Virus Research, Kyoto University Kyoto, Japan, for providing the Hes1 promoter-luciferase construct; Dr Shereen Ezzat, Departments of Medicine, Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada for providing Human FGFR4 promoter constructs; Dr Asok Antony, Indiana University Medical School, Indianapolis, IN, USA for providing the FRa expression construct in pcDNA3 and GST-FRa plasmids; and William Goossens, manager of the Microscopy and Imaging Facility at Children{\textquoteright}s Hospital of Chicago Research Center for assistance with confocal microscopy. We thank Bio-Rad for their generous gift of Trans-Blot Turbo and the ChemiDocMP system.",

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AU - Tsurubuchi, Takao

AU - Ichi, Shunsuke

AU - Szany, Elise V.

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AU - Mania-Farnell, Barbara

AU - McLone, David G.

AU - Tomita, Tadanori

AU - Mayanil, C. Shekhar

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

Abstract

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ASJC Scopus subject areas

UN SDGs

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