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Upregulation of human PINK1 gene expression by NFκB signalling Duan, Xiaoling; Tong, Jade; Xu, Qin; Wu, Yili; Cai, Fang; Li, Tingyu; Song, Weihong

Abstract

Parkinson’s disease (PD) is one of the major neurodegenerative disorders. Mitochondrial malfunction is implicated in PD pathogenesis. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN)-induced putative kinase 1 (PINK1), a serine/threonine kinase, plays an important role in the quality control of mitochondria and more than 70 PINK1 mutations have been identified to cause early-onset PD. However, the regulation of PINK1 gene expression remains elusive. In the present study, we identified the transcription start site (TSS) of the human PINK1 gene using switching mechanism at 5’end of RNA transcription (SMART RACE) assay. The TSS is located at 91 bp upstream of the translation start site ATG. The region with 104 bp was identified as the minimal promoter region by deletion analysis followed by dual luciferase assay. Four functional cis-acting nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB)-binding sites within the PINK1 promoter were identified. NFκB overexpression led to the up-regulation of PINK1 expression in both HEK293 cells and SH-SY5Y cells. Consistently, lipopolysaccharide (LPS), a strong activator of NFκB, significantly increased PINK1 expression in SH-SY5Y cells. Taken together, our results clearly suggested that PINK1 expression is tightly regulated at its transcription level and NFκB is a positive regulator for PINK1 expression.

Item Metadata

Title
Upregulation of human PINK1 gene expression by NFκB signalling
Creator
Duan, Xiaoling; Tong, Jade; Xu, Qin; Wu, Yili; Cai, Fang; Li, Tingyu; Song, Weihong
Contributor
University of British Columbia. Djavad Mowafaghian Centre for Brain Health
Publisher
BioMed Central
Date Issued
2014-08-11
Description
Parkinson’s disease (PD) is one of the major neurodegenerative disorders. Mitochondrial malfunction is implicated in PD pathogenesis. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN)-induced putative kinase 1 (PINK1), a serine/threonine kinase, plays an important role in the quality control of mitochondria and more than 70 PINK1 mutations have been identified to cause early-onset PD. However, the regulation of PINK1 gene expression remains elusive. In the present study, we identified the transcription start site (TSS) of the human PINK1 gene using switching mechanism at 5’end of RNA transcription (SMART RACE) assay. The TSS is located at 91 bp upstream of the translation start site ATG. The region with 104 bp was identified as the minimal promoter region by deletion analysis followed by dual luciferase assay. Four functional cis-acting nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB)-binding sites within the PINK1 promoter were identified. NFκB overexpression led to the up-regulation of PINK1 expression in both HEK293 cells and SH-SY5Y cells. Consistently, lipopolysaccharide (LPS), a strong activator of NFκB, significantly increased PINK1 expression in SH-SY5Y cells. Taken together, our results clearly suggested that PINK1 expression is tightly regulated at its transcription level and NFκB is a positive regulator for PINK1 expression.
Subject
PINK1; Mitochondrial function; NFκB; Transcription
Genre
Article
Type
Text
Language
eng
Date Available
2015-08-25
Provider
Vancouver : University of British Columbia Library
Rights
Attribution 4.0 International (CC BY 4.0)
DOI
10.14288/1.0074638
URI
http://hdl.handle.net/2429/54623
Affiliation
Psychiatry, Department of; Non UBC; Medicine, Faculty of
Citation
Molecular Brain. 2014 Aug 11;7(1):57
Publisher DOI
10.1186/s13041-014-0057-y
Peer Review Status
Reviewed
Scholarly Level
Faculty
Copyright Holder
Duan et al.
Rights URI
http://creativecommons.org/licenses/by/4.0/
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DSpace

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Attribution 4.0 International (CC BY 4.0)