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Open Access Research article

Transcriptional Regulation of TMP21 by NFAT

Shengchun Liu12*, Si Zhang2, Kelley Bromley-Brits2, Fang Cai2, Weihui Zhou2, Kun Xia3, Jill Mittelholtz2 and Weihong Song2*

Author Affiliations

1 Department of Surgery, The First Affiliated Hospital, Chongqing University of Medical Sciences, Chongqing 410006, China

2 Townsend Family Laboratories, Department of Psychiatry, Brain Research Center, Graduate Program in Neuroscience, The University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada

3 The State Key Lab of Medical Genetics of China, Central South University, Changsha, Hunan 410078, China

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Molecular Neurodegeneration 2011, 6:21  doi:10.1186/1750-1326-6-21

Published: 7 March 2011

Abstract

Background

TMP21 is a member of the p24 cargo protein family, which is involved in protein transport between the Golgi apparatus and ER. Alzheimer's Disease (AD) is the most common neurodegenerative disorder leading to dementia and deposition of amyloid β protein (Aβ) is the pathological feature of AD pathogenesis. Knockdown of TMP21 expression by siRNA causes a sharp increase in Aβ production; however the underlying mechanism by which TMP21 regulates Aβ generation is unknown, and human TMP21 gene expression regulation has not yet been studied.

Results

In this report we have cloned a 3.3-kb fragment upstream of the human TMP21 gene. The transcription start site (TSS) of the human TMP21 gene was identified. A series of nested deletions of the 5' flanking region of the human TMP21 gene were subcloned into the pGL3-basic luciferase reporter plasmid. We identified the -120 to +2 region as containing the minimal sequence necessary for TMP21 gene promoter activity. Gel shift assays revealed that the human TMP21 gene promoter contains NFAT response elements. Expression of NFAT increased TMP21 gene expression and inhibition of NFAT by siRNA reduced TMP21 gene expression.

Conclusion

NFAT plays a very important role in the regulation of human TMP21 gene expression. This study demonstrates that the human TMP21 gene expression is transcriptionally regulated by NFAT signaling.