The tert-butylhydroquinone-mediated activation of the human thioredoxin gene reveals a novel promoter structure

Osborne, SA, Hawkes, HJK, Baldwin, BL, Alexander, KA, Svingen, T, Clarke, FM and Tonissen, KF (2006) The tert-butylhydroquinone-mediated activation of the human thioredoxin gene reveals a novel promoter structure. Biochemical Journal, 398 2: 269-277. doi:10.1042/BJ20060076


Author Osborne, SA
Hawkes, HJK
Baldwin, BL
Alexander, KA
Svingen, T
Clarke, FM
Tonissen, KF
Title The tert-butylhydroquinone-mediated activation of the human thioredoxin gene reveals a novel promoter structure
Journal name Biochemical Journal   Check publisher's open access policy
ISSN 0264-6021
Publication date 2006-09-01
Sub-type Article (original research)
DOI 10.1042/BJ20060076
Volume 398
Issue 2
Start page 269
End page 277
Total pages 9
Place of publication United Kingdom
Publisher Portland Press
Language eng
Formatted abstract
Thioredoxin is a redox-active protein that plays multiple roles in regulating cell growth, cell signalling and apoptosis. Here, we have demonstrated that a complex mechanism involving multiple regulatory elements is involved in the tBHQ [tert-butylhydroquinone or 2,5-di-(t-butyl)-1,4- hydroquinone]-mediated activation of the thioredoxin gene. Luciferase assays, utilizing various wild-type and mutated thioredoxin promoter fragments, revealed roles for the ORE (oxidative stress responsive element), ARE (antioxidant responsive element), three Sp1 (specificity protein 1)-binding sites and the TATA box in the activation of the thioredoxin gene by tBHQ. The ORE required the presence of the ARE to elicit its response, whereas the independent removal of three Sp1-binding sites and the TATA box also decreased activation of the thioredoxin gene, with mutation of the TATA box having the greatest effect. Real-time RT (reverse transcriptase)-PCR analysis also revealed varying roles for two TSSs (transcription start sites) in the activation of the thioredoxin gene by tBHQ. Transcription was initiated from both TSSs; however, different response rates and fold inductions were observed. Together, these results suggest that the thioredoxin gene is controlled by a novel arrangement of two overlapping core promoter regions, one containing a TATA box and the other TATA-less. Altering the intracellular levels of thioredoxin in a breast cancer cell line also influenced the induction of thioredoxin transcription in response to tBHQ. Stable transfections with a redox-inactive thioredoxin mutant produced 3.6 times higher induction levels of thioredoxin transcription compared with control cells, indicating an intrinsic form of control of promoter activity by the thioredoxin system itself. © 2006 Biochemical Society.
Keyword Antioxidant responsive element
Oxidative stress
Specificity protein 1 (Sp1)
Tert-butylhydroquinone
Thioredoxin
Transcriptional Activation
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 9 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 05 May 2011, 00:14:06 EST by Dr Terje Svingen on behalf of Institute for Molecular Bioscience