Document Detail

Thioredoxin modulates activator protein 1 (AP-1) activity and p27Kip1 degradation through direct interaction with Jab1.
MedLine Citation:
PMID:  15480426     Owner:  NLM     Status:  MEDLINE    
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.
Chae Young Hwang; Yeung Sook Ryu; Mi-Sun Chung; Kwang Dong Kim; Sung Sup Park; Suhn-Kee Chae; Ho Zoon Chae; Ki-Sun Kwon
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncogene     Volume:  23     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  2004 Nov 
Date Detail:
Created Date:  2004-11-26     Completed Date:  2004-12-17     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  8868-75     Citation Subset:  IM    
Center for Systems Biology, Korea Research Institute of Bioscience and Biotechnology, Taejon 305-333, Korea.
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MeSH Terms
Binding Sites
Cell Cycle Proteins / metabolism*
Cell Line
Cell Proliferation
Cyclin-Dependent Kinase Inhibitor p27
Cysteine / chemistry
DNA, Complementary / metabolism
DNA-Binding Proteins / metabolism*
Disease Progression
Fluorescence Resonance Energy Transfer
Gene Expression Regulation
Genes, Reporter
Glutathione Transferase / metabolism
Hela Cells
Intracellular Signaling Peptides and Proteins
Neoplasms / metabolism
Oligonucleotides, Antisense / chemistry
Peptide Hydrolases
Protein Binding
Recombinant Proteins / chemistry
Signal Transduction
Thioredoxins / metabolism*
Time Factors
Transcription Factor AP-1 / metabolism*
Transcription Factors / metabolism*
Transcriptional Activation
Tumor Suppressor Proteins / metabolism*
Two-Hybrid System Techniques
Reg. No./Substance:
0/Cell Cycle Proteins; 0/DNA, Complementary; 0/DNA-Binding Proteins; 0/Disulfides; 0/Intracellular Signaling Peptides and Proteins; 0/Oligonucleotides, Antisense; 0/Recombinant Proteins; 0/Transcription Factor AP-1; 0/Transcription Factors; 0/Tumor Suppressor Proteins; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; 52-90-4/Cysteine; 52500-60-4/Thioredoxins; EC Transferase; EC 3.4.-/Peptide Hydrolases; EC 3.4.-.-/COPS5 protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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