1. Thioredoxin modulates activator protein 1 (AP-1) activity and p27Kip1 degradation through direct interaction with Jab1
- Author
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Chae Young Hwang, Yeung Sook Ryu, Ho Zoon Chae, Mi-Sun Chung, Suhn-Kee Chae, Sung Sup Park, Ki-Sun Kwon, and Kwang Dong Kim
- Subjects
Transcriptional Activation ,Cancer Research ,animal structures ,DNA, Complementary ,Time Factors ,Cell Cycle Proteins ,Biology ,Cell Line ,Thioredoxins ,Genes, Reporter ,Neoplasms ,Two-Hybrid System Techniques ,Coactivator ,Genetics ,Fluorescence Resonance Energy Transfer ,Humans ,Immunoprecipitation ,Cysteine ,Disulfides ,Molecular Biology ,Cell Proliferation ,Glutathione Transferase ,Binding Sites ,Kinase ,COP9 Signalosome Complex ,Binding protein ,Tumor Suppressor Proteins ,Intracellular Signaling Peptides and Proteins ,Cell cycle ,Cyclin-Dependent Kinase Inhibitor 1B ,Oligonucleotides, Antisense ,Prognosis ,Recombinant Proteins ,DNA-Binding Proteins ,Transcription Factor AP-1 ,Gene Expression Regulation ,Transcription Coactivator ,Mutation ,Cancer research ,Disease Progression ,Signal transduction ,Thioredoxin ,Oxidation-Reduction ,Cyclin-Dependent Kinase Inhibitor p27 ,HeLa Cells ,Peptide Hydrolases ,Protein Binding ,Signal Transduction ,Transcription Factors - Abstract
Thioredoxin (Trx) is a cellular redox enzyme that plays multiple roles in regulating cell growth and apoptosis. Jun activation domain-binding protein 1 (Jab1) was originally identified as a coactivator of activator protein 1 (AP-1) transcription and was also shown to promote degradation of the cyclin-dependent kinase inhibitor, p27Kip1. Recently, Jab1 expression was associated with the progression and poor prognosis of pituitary, epithelial ovarian, and breast cancers, suggesting that it plays a role in oncogenesis. Here, we report that Trx specifically interacts with and modulates the function of Jab1. Fluorescence resonance energy transfer and co-immunoprecipitation studies revealed that Trx and Jab1 colocalize and directly interact with each other. Further, Trx negatively regulates two important Jab1-controlled signaling pathways, activation of AP-1 transcription and degradation of p27Kip1, probably through a direct interaction between Trx and C-terminal of Jab1. The negative effect of Trx on AP-1 activity is Jab1-dependent, as it disappears when Jab1 levels are suppressed by an antisense approach. In addition, Trx competes with p27Kip1 for Jab1 binding. Taken together, our results suggest that Trx may regulate cell cycle and growth through a novel modulation of Jab1-mediated proliferation signals, further indicating that Trx may have the ability to control tumor progression.
- Published
- 2004