Nucleoredoxin, Glutaredoxin, and Thioredoxin Differentially Regulate NF-κB, AP-1, and CREB Activation in HEK293 Cells

Hirota, Kaoru; Matsui, Masanao; Murata, Miyahiko; Takashima, Yuichiro; Cheng, Fen; Itoh, Takafumi; Fukuda, Kazuhiko; Yodoi, Junji

doi:10.1006/bbrc.2000.3106

Cited by 184 publications

(101 citation statements)

References 26 publications

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“…In the pcDNA-X cells, a threefold increase in AP-1 DNA -binding activity was observed following IR ( Figure 3a, lanes 1 vs 4) while pcDNA-TRX-wt cells demonstrated a constitutive threefold increase in DNA-binding activity that increased slightly following IR exposure (lanes 2 vs 5). These results are similar to those observed by Hirota et al (2000a) using transient co-transfection assays and suggests that AP-1 activity is nearmaximally activated in cell lines overexpressing TRX. In contrast, no induction of AP-1 DNA-binding was observed in pcDNA-TRX-dm cells (lanes 3 vs 6) exposed to IR.…”

Section: Characterization Of Trx and Tr Overexpressing Cell Linessupporting

confidence: 88%

“…As such, pCXN2-myc-X, pCXN2-myc-TR-wt, and pCXN2-myc-mTR cells were harvested without and with exposure to IR and the nuclear immunoreactive TRX levels were determined. The pCXN2-myc-X cells without and with exposure to IR are shown (Figure 5a, lanes 1 vs 4) and demonstrated TRX nuclear translocation following IR exposure, as has been shown by others (Hirota et al, 1999(Hirota et al, , 2000aWei et al, 2000). This result is identical to that observed in the parental HeLa cell line exposed to IR (Wei et al, 2000) and acts as a positive control.…”

Section: Trx Nuclear Translocation Is Altered In Tr Overexpressing Cellssupporting

confidence: 81%

“…The role of TRX in the regulation of AP-1 DNAbinding activity following IR, as well as other environmental stress inducing agents (Hirota et al, 1999(Hirota et al, , 2000a, has been well established. However, the role of the critical cysteines in IR-induced induction of the AP-1 complex has not been investigated.…”

Section: Characterization Of Trx and Tr Overexpressing Cell Linesmentioning

confidence: 99%

“…One intracellular function of TRX is to activate protein-nucleic acid interactions of nuclear transcription factors via redox regulation (Hirota et al, 1999(Hirota et al, , 2000aWei et al, 2000). It has been previously shown that following exposure to IR (Wei et al, 2000) or other oxidants (Hirota et al, 1999(Hirota et al, , 2000a, TRX translocates into the nucleus, where it interacts with another redox-sensitive signaling protein, redox factor-1, and appears to regulate the nuclear transcription factor complex, AP-1.…”

Section: Introductionmentioning

confidence: 99%

“…It has been previously shown that following exposure to IR (Wei et al, 2000) or other oxidants (Hirota et al, 1999(Hirota et al, , 2000a, TRX translocates into the nucleus, where it interacts with another redox-sensitive signaling protein, redox factor-1, and appears to regulate the nuclear transcription factor complex, AP-1. The current study demonstrates the essential role of TR as a redox-sensitive signaling factor functioning upstream of TRX in the regulation of AP-1 activity and demonstrates that the active site cysteine residues are essential in mediating IR-induced activation as well as the regulation of stress-induced TRX nuclear translocation.…”

Section: Introductionmentioning

confidence: 99%

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Thioredoxin reductase regulates AP-1 activity as well as thioredoxin nuclear localization via active cysteines in response to ionizing radiation

et al. 2002

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A recently identified class of signaling factors uses critical cysteine motif(s) that act as redox-sensitive 'sulfhydryl switches' to reversibly modulate specific signal transduction cascades regulating downstream proteins with similar redox-sensitive sites. For example, signaling factors such as redox factor-1 (Ref-1) and transcription factors such as the AP-1 complex both contain redox-sensitive cysteine motifs that regulate activity in response to oxidative stress. The mammalian thioredoxin reductase-1 (TR) is an oxidoreductase selenocysteine-containing flavoprotein that also appears to regulate multiple downstream intracellular redoxsensitive proteins. Since ionizing radiation (IR) induces oxidative stress as well as increases AP-1 DNA-binding activity via the activation of Ref-1, the potential roles of TR and thioredoxin (TRX) in the regulation of AP-1 activity in response to IR were investigated. Permanently transfected cell lines that overexpress wild type TR demonstrated constitutive increases in AP-1 DNAbinding activity as well as AP-1-dependent reporter gene expression, relative to vector control cells. In contrast, permanently transfected cell lines expressing a TR gene with the active site cysteine motif deleted were unable to induce AP-1 activity or reporter gene expression in response to IR. Transient genetic overexpression of either the TR wild type or dominant-negative genes demonstrated similar results using a transient assay system. One mechanism through which TR regulates AP-1 activity appears to involve TRX sub-cellular localization, with no change in the total TRX content of the cell. These results identify a novel function of the TR enzyme as a signaling factor in the regulation of AP-1 activity via a cysteine motif located in the protein.

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Section: Characterization Of Trx and Tr Overexpressing Cell Linessupporting

confidence: 88%

Section: Trx Nuclear Translocation Is Altered In Tr Overexpressing Cellssupporting

confidence: 81%

Section: Characterization Of Trx and Tr Overexpressing Cell Linesmentioning

confidence: 99%