Characterization of NFE2L1-616, an isoform of nuclear factor-erythroid-2 related transcription factor-1 that activates antioxidant response element-regulated genes

Abstract The NFE2L1 transcription factor (aka Nrf1) is a basic leucine zipper protein that performs a critical role in the cellular stress response pathway. Here, we characterized a novel variant of NFE2L1 referred to as NFE2L1-616. The transcript encoding NFE2L1-616 is derived from an intronic prom...

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Main Authors: Daniel V. Ho, Kaylen G. Suryajaya, Kaitlyn Manh, Amanda N. Duong, Jefferson Y. Chan
Format: Article
Language:English
Published: Nature Portfolio 2023-11-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-47055-2
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author Daniel V. Ho
Kaylen G. Suryajaya
Kaitlyn Manh
Amanda N. Duong
Jefferson Y. Chan
author_facet Daniel V. Ho
Kaylen G. Suryajaya
Kaitlyn Manh
Amanda N. Duong
Jefferson Y. Chan
author_sort Daniel V. Ho
collection DOAJ
description Abstract The NFE2L1 transcription factor (aka Nrf1) is a basic leucine zipper protein that performs a critical role in the cellular stress response pathway. Here, we characterized a novel variant of NFE2L1 referred to as NFE2L1-616. The transcript encoding NFE2L1-616 is derived from an intronic promoter, and it has a distinct first exon than other reported full-length NFE2L1 isoforms. The NFE2L1-616 protein constitutively localizes in the nucleus as it lacks the N-terminal amino acid residues that targets other full-length NFE2L1 isoforms to the endoplasmic reticulum. The expression level of NFE2L1-616 is lower than other NFE2L1 isoforms. It is widely expressed across different cell lines and tissues that were examined. NFE2L1-616 showed strong transcriptional activity driving luciferase reporter expression from a promoter containing antioxidant response element. Together, the results suggest that NFE2L1-616 variant can function as a positive regulator in the transcriptional regulation of NFE2L1 responsive genes.
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spelling doaj.art-20d3dc802ade4991afe65c95e9fb180b2023-11-20T09:21:15ZengNature PortfolioScientific Reports2045-23222023-11-0113111210.1038/s41598-023-47055-2Characterization of NFE2L1-616, an isoform of nuclear factor-erythroid-2 related transcription factor-1 that activates antioxidant response element-regulated genesDaniel V. Ho0Kaylen G. Suryajaya1Kaitlyn Manh2Amanda N. Duong3Jefferson Y. Chan4Department of Laboratory Medicine and Pathology, University of California, IrvineDepartment of Laboratory Medicine and Pathology, University of California, IrvineDepartment of Laboratory Medicine and Pathology, University of California, IrvineDepartment of Laboratory Medicine and Pathology, University of California, IrvineDepartment of Laboratory Medicine and Pathology, University of California, IrvineAbstract The NFE2L1 transcription factor (aka Nrf1) is a basic leucine zipper protein that performs a critical role in the cellular stress response pathway. Here, we characterized a novel variant of NFE2L1 referred to as NFE2L1-616. The transcript encoding NFE2L1-616 is derived from an intronic promoter, and it has a distinct first exon than other reported full-length NFE2L1 isoforms. The NFE2L1-616 protein constitutively localizes in the nucleus as it lacks the N-terminal amino acid residues that targets other full-length NFE2L1 isoforms to the endoplasmic reticulum. The expression level of NFE2L1-616 is lower than other NFE2L1 isoforms. It is widely expressed across different cell lines and tissues that were examined. NFE2L1-616 showed strong transcriptional activity driving luciferase reporter expression from a promoter containing antioxidant response element. Together, the results suggest that NFE2L1-616 variant can function as a positive regulator in the transcriptional regulation of NFE2L1 responsive genes.https://doi.org/10.1038/s41598-023-47055-2
spellingShingle Daniel V. Ho
Kaylen G. Suryajaya
Kaitlyn Manh
Amanda N. Duong
Jefferson Y. Chan
Characterization of NFE2L1-616, an isoform of nuclear factor-erythroid-2 related transcription factor-1 that activates antioxidant response element-regulated genes
Scientific Reports
title Characterization of NFE2L1-616, an isoform of nuclear factor-erythroid-2 related transcription factor-1 that activates antioxidant response element-regulated genes
title_full Characterization of NFE2L1-616, an isoform of nuclear factor-erythroid-2 related transcription factor-1 that activates antioxidant response element-regulated genes
title_fullStr Characterization of NFE2L1-616, an isoform of nuclear factor-erythroid-2 related transcription factor-1 that activates antioxidant response element-regulated genes
title_full_unstemmed Characterization of NFE2L1-616, an isoform of nuclear factor-erythroid-2 related transcription factor-1 that activates antioxidant response element-regulated genes
title_short Characterization of NFE2L1-616, an isoform of nuclear factor-erythroid-2 related transcription factor-1 that activates antioxidant response element-regulated genes
title_sort characterization of nfe2l1 616 an isoform of nuclear factor erythroid 2 related transcription factor 1 that activates antioxidant response element regulated genes
url https://doi.org/10.1038/s41598-023-47055-2
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