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AMPK regulates nuclear trafficking of Nrf2 through phosphorylation
Author(s) -
Joo Min Sung,
Kim Won Dong,
Kim Sang Geon
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.864.14
Subject(s) - ampk , nuclear export signal , microbiology and biotechnology , phosphorylation , nuclear transport , protein kinase a , transcription factor , chemistry , nuclear localization sequence , cell nucleus , signal transduction , amp activated protein kinase , biology , nucleus , gene , biochemistry
Nrf2 is a key transcription factor for the induction of antioxidant genes. AMPK functions as a central regulator of cell survival in response to stressful stimuli. Nrf2 should be coordinated with the cell survival pathway controlled by AMPK, but so far the mechanistic connections remain undefined. This study investigated the regulatory role of AMPK in the nuclear trafficking of Nrf2 and its activity regulation. The network integrating neighbor molecules of AMPK and Nrf2 suggested direct interaction between AMPK and Nrf2. In a cell model, AMPK activation by AICAR treatment caused nuclear accumulation of Nrf2. In the in vitro kinase and peptide competition assays, AMPK directly phosphorylated Nrf2 at Ser550 residue located in the canonical nuclear export signal. Nrf2‐S550A mutation failed to be accumulated in the nucleus by AMPK activation. Leptomycin B, a nuclear export inhibitor, did not enhance nuclear accumulation of WT‐Nrf2 by AICAR. These results demonstrate that AMPK phosphorylates Nrf2 at Ser550 residue and thereby promotes nuclear accumulation of Nrf2 by preventing its nuclear export.