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Phosphorylation of Tyrosine 568 Controls Nuclear Export of Nrf2

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Jain, Abhinav K., Jaiswal, Anil K.·2006·Journal of Biological Chemistry

Abstract

Nuclear factor Nrf 2, under normal conditions, is retained in the cytosol by INrf 2. Antioxidants and oxidants antagonize this interaction, resulting in the release of Nrf 2. Nrf 2 translocates to the nucleus binds to ARE and activates a battery of chemopreventive genes. Once this is achieved, Nrf 2 is exported out of the nucleus, binds with INrf 2, and degrades. Nrf 2 contains well defined signals that control nuclear import and export of Nrf 2. The present studies demonstrate that phosphorylation of tyrosine 568 is required for Crm1-mediated nuclear export and degradation of Nrf 2. Mutation of tyrosine 568 to alanine and phenylalanine resulted in the loss of interaction with Crm1 and abrogation of nuclear export of Nrf 2. Nrf 2Y568A is deficient in nuclear export and displays delayed degradation compared with wild-type Nrf 2. In addition, Src inhibitor PP2 caused nuclear accumulation of Nrf 2 in normal and hydrogen peroxide-treated cells but had no effect on localization of mutant Nrf 2Y568A. Further experiments with small interfering RNA revealed that Fyn phosphorylated Nrf 2Y568 leading to nuclear export and degradation of Nrf 2.

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Metadata

Authors
Jain, A. K., & Jaiswal, A. K.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2006-04
Volume
281
Issue
17
Pages
12132-12142
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2051520394
Cited by
172
References
5
FWCI
3.32
Type
journal article
Language
en
Status
Retracted
Open access
hybrid

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CoChat. (2026). Citation check: Phosphorylation of Tyrosine 568 Controls Nuclear Export of Nrf2. https://app.cochat.ai/papers/10.1074/jbc.m511198200
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Jain, A. K., & Jaiswal, A. K. (2006). Phosphorylation of Tyrosine 568 Controls Nuclear Export of Nrf2. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m511198200

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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