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Phosphorylation of Nrf2 in the transcription activation domain by casein kinase 2 (CK2) is critical for the nuclear translocation and transcription activation function of Nrf2 in IMR-32 neuroblastoma cells.

Authors
Apopa-PL; He-X; Ma-Q
Source
J Biochem Mol Toxicol 2008 Feb; 22(1):63-76
NIOSHTIC No.
20033376
Abstract
The antioxidant-activated transcription factor Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) controls the induction of cytoprotective and detoxification genes against toxic materials and oxidative injuries. The signaling events leading to the activation of Nrf2 has not been clear; in particular, the role of phosphorylation in Nrf2 function remains controversial. We report that phenolic compounds, like antioxidant tert-butylhydroquinone (tBHQ) induced two forms of the Nrf2 protein in neuroblastoma cells (IMR-32), which migrated as distinctive bands on SDS-PAGE. In vitro treatment with lambda phosphatase eliminated the slower migrating form of Nrf2. The phosphorylated form of Nrf2 preferentially localized in the nucleus. Deletional analyses revealed that the transcription activation (TA) domain is phosphorylated. The TA domain is characterized by the presence of multiple conserved phosphorylation sites of CK2. Treatments with CK2 inhibitor DMAT blocked the induction of endogenous target genes of Nrf2 in cells and inhibited the TA activity of Nrf2. The findings demonstrated that phosphorylation of Nrf2 at the TA domains by CK2 is an integral component of Nrf2 activation.
Keywords
Cellular-function; Cellular-structures; Cell-differentiation; Cell-function; Cell-biology; Genetic-factors; Brain-disorders; Antioxidants; Antioxidation
Contact
Qiang Ma, Receptor Biology Laboratory, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV 26505
CODEN
JBMTFQ
Publication Date
20080201
Document Type
Journal Article; Academic/Scholarly
Email Address
qaml@cdc.gov
Fiscal Year
2008
NTIS Accession No.
NTIS Price
Issue of Publication
1
ISSN
1095-6670
NIOSH Division
HELD
Source Name
Journal of Biochemical and Molecular Toxicology
State
WV
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