Thioredoxin modulates activator protein 1 (AP-1) activity and p27Kip1 degradation through direct interaction with Jab1

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Title
Thioredoxin modulates activator protein 1 (AP-1) activity and p27Kip1 degradation through direct interaction with Jab1
Author(s)
Chae Young Hwang; Yeung Sook Ryu; Mi Sun Chung; Kwang Dong Kim; Sung Sup Park; S K Chae; H Z Chae; Ki Sun Kwon
Bibliographic Citation
Oncogene, vol. 23, no. 55, pp. 8868-8875
Publication Year
2004
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.
Keyword
cell cycleredox signalingtranscription coactivatortumor progression
ISSN
0950-9232
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/sj.onc.1208116
Type
Article
Appears in Collections:
Aging Convergence Research Center > 1. Journal Articles
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