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          Institute: MPI für molekulare Genetik     Collection: Department of Vertebrate Genomics     Display Documents

ID: 271601.0, MPI für molekulare Genetik / Department of Vertebrate Genomics
Nuclear Oncoprotein Prothymosin {alpha} Is a Partner of Keap1: Implications for Expression of Oxidative Stress-Protecting Genes
Authors:Karapetian, Ruben N.; Evstafieva, Alexandra G.; Abaeva, Irina S.; Chichkova, Nina V.; Filonov, Grigoriy S.; Rubtsov, Yuri P.; Sukhacheva, Elena A.; Melnikov, Sergey V.; Schneider, Ulrich; Wanker, Erich E.; Vartapetian, Andrey B.
Date of Publication (YYYY-MM-DD):2005-02
Title of Journal:Molecular and Cellular Biology (Washington, DC)
Journal Abbrev.:Mol Cell Biol
Issue / Number:3
Start Page:1089
End Page:1099
Copyright:© 2005, American Society for Microbiology
Review Status:not specified
Audience:Experts Only
Abstract / Description:Animal cells counteract oxidative stress and electrophilic attack through coordinated expression of a set of detoxifying and antioxidant enzyme genes mediated by transcription factor Nrf2. In unstressed cells, Nrf2 appears to be sequestered in the cytoplasm via association with an inhibitor protein, Keap1. Here, by using the yeast two-hybrid screen, human Keap1 has been identified as a partner of the nuclear protein prothymosin {alpha}. The in vivo and in vitro data indicated that the prothymosin {alpha}-Keap1 interaction is direct, highly specific, and functionally relevant. Furthermore, we showed that Keap1 is a nuclear-cytoplasmic shuttling protein equipped with a nuclear export signal that is important for its inhibitory action. Prothymosin {alpha} was able to liberate Nrf2 from the Nrf2-Keap1 inhibitory complex in vitro through competition with Nrf2 for binding to the same domain of Keap1. In vivo, the level of Nrf2-dependent transcription was correlated with the intracellular level of prothymosin {alpha} by using prothymosin {alpha} overproduction and mRNA interference approaches. Our data attribute to prothymosin {alpha} the role of intranuclear dissociator of the Nrf2-Keap1 complex, thus revealing a novel function for prothymosin {alpha} and adding a new dimension to the molecular mechanisms underlying expression of oxidative stress-protecting genes.
Comment of the Author/Creator:Email: varta@genebee.msu.su
External Publication Status:published
Document Type:Article
Communicated by:Hans Lehrach
Affiliations:MPI für molekulare Genetik
External Affiliations:Belozersky Institute of Physico-Chemical Biology, Moscow State University;
Shemiakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia;
Max Delbrueck Center for Molecular Medicine, Berlin, Germany
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