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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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Genre: Zeitschriftenartikel
Alternativer Titel : Mol Cell Biol

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Karapetian et al. - Mol Cell Biol.pdf (beliebiger Volltext), 602KB
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 Urheber:
Karapetian, Ruben N., Autor
Evstafieva, Alexandra G., Autor
Abaeva, Irina S., Autor
Chichkova, Nina V., Autor
Filonov, Grigoriy S., Autor
Rubtsov, Yuri P., Autor
Sukhacheva, Elena A., Autor
Melnikov, Sergey V., Autor
Schneider, Ulrich1, Autor
Wanker, Erich E., Autor
Vartapetian, Andrey B., Autor
Affiliations:
1Max Planck Society, ou_persistent13              

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 Zusammenfassung: 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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Sprache(n): eng - English
 Datum: 2005-02
 Publikationsstatus: Erschienen
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 Identifikatoren: eDoc: 271601
DOI: 10.1128/MCB.25.3.1089-1099.2005
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Titel: Molecular and Cellular Biology (Washington, DC)
  Alternativer Titel : Mol Cell Biol
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 25 (3) Artikelnummer: - Start- / Endseite: 1089 - 1099 Identifikator: ISSN: 0270-7306