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  Nuclear Oncoprotein Prothymosin {alpha} Is a Partner of Keap1: Implications for Expression of Oxidative Stress-Protecting Genes

Karapetian, R. N., Evstafieva, A. G., Abaeva, I. S., Chichkova, N. V., Filonov, G. S., Rubtsov, Y. P., et al. (2005). Nuclear Oncoprotein Prothymosin {alpha} Is a Partner of Keap1: Implications for Expression of Oxidative Stress-Protecting Genes. Molecular and Cellular Biology (Washington, DC), 25(3), 1089-1099. doi:10.1128/MCB.25.3.1089-1099.2005.

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Item Permalink: https://hdl.handle.net/11858/00-001M-0000-0010-8705-B Version Permalink: https://hdl.handle.net/11858/00-001M-0000-0010-8706-9
Genre: Journal Article
Alternative Title : Mol Cell Biol

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Karapetian, Ruben N., Author
Evstafieva, Alexandra G., Author
Abaeva, Irina S., Author
Chichkova, Nina V., Author
Filonov, Grigoriy S., Author
Rubtsov, Yuri P., Author
Sukhacheva, Elena A., Author
Melnikov, Sergey V., Author
Schneider, Ulrich1, Author
Wanker, Erich E., Author
Vartapetian, Andrey B., Author
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1Max Planck Society, ou_persistent13              

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 Abstract: 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.

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Language(s): eng - English
 Dates: 2005-02
 Publication Status: Issued
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 Rev. Type: -
 Identifiers: eDoc: 271601
DOI: 10.1128/MCB.25.3.1089-1099.2005
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Title: Molecular and Cellular Biology (Washington, DC)
  Alternative Title : Mol Cell Biol
Source Genre: Journal
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Pages: - Volume / Issue: 25 (3) Sequence Number: - Start / End Page: 1089 - 1099 Identifier: ISSN: 0270-7306