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Mol Cell Biochem. 2010 Apr;337(1-2):53-63. doi: 10.1007/s11010-009-0285-0. Epub 2009 Oct 27.

c-Jun-NH2 terminal kinase (JNK)-mediates AP-1 activation by thioredoxin: phosphorylation of cJun, JunB, and Fra-1.

Author information

1
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. kdas@uams.edu

Abstract

Thioredoxin (Trx) is a small ubiquitous protein, which has been shown to be involved in redox-dependent cellular functions. In this article, we demonstrate that the increased level of Trx induces AP-1 DNA binding in a redox-dependent manner by activating JNK subgroup of MAPKs. The majority of AP-1 DNA binding complex was found to be composed of cJun, JunB, and Fra-1. Increased expression of Trx resulted in phosphorylation of cJun, Jun B, and Fra-1. Further, increased expression of Trx induced the phosphorylation of MKK4 and MKK7 which are upstream kinases of the JNK signaling cascade. In co-transfection studies, AP-1-dependent luciferase reporter vector and pcDNA3-Trx increased luciferase activity demonstrating that increased expression of Trx increases AP-1 transactivation. In addition, dominant-negative JNK kinase (dnJNK/MKK4) or dominant-negative JNK (dnJNK) inhibited Trx-mediated AP-1 transactivation, as well as AP-1 DNA binding. Furthermore, transfection of kinase-dead MEKK1, an initiating kinase of the JNK pathway inhibited Trx-mediated AP-1 transactivation and DNA binding, suggesting that MEKK1 may mediate Trx-induced AP-1 activation. In contrast, wild-type MEKK1 overexpression did not inhibit Trx-mediated AP-1 activation. Taken together, our data demonstrate that increased expression of Trx induces MKK4/MKK7-dependent JNK activation, resulting in enhanced DNA binding, and transactivation of AP-1 transcription factor.

PMID:
19859790
DOI:
10.1007/s11010-009-0285-0
[Indexed for MEDLINE]

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