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Title 

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

Authors 

Chae Young HwangYeung Sook RyuMi Sun ChungKwang Dong KimSung Sup ParkS K ChaeH Z ChaeKi Sun Kwon

Publisher 

Nature Publishing Group

Issue Date 

2004

Citation 

Oncogene, vol. 23, no. 55, pp. 8868-8875

Keywords 

cell cycleredox signalingtranscription coactivatortumor progressionbinding proteincyclin dependent kinase inhibitor 1Bprotein Jab1protein p27thioredoxintranscription factor AP 1

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.

ISSN 

0950-9232

Link 

http://dx.doi.org/10.1038/sj.onc.1208116

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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