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Sumoylation impacts the transcriptional activity of Nrf2 and is necessary for its localization to promyelocytic leukemia nuclear bodies
Author(s) -
Theodore Melanie,
McIntosh Deneshia,
Kawai Yumiko,
Arinze Ifeanyi J.
Publication year - 2010
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.24.1_supplement.859.4
Subject(s) - sumo protein , transcription factor , promoter , transfection , promyelocytic leukemia protein , green fluorescent protein , transcription (linguistics) , reporter gene , microbiology and biotechnology , biology , keap1 , acute promyelocytic leukemia , gene , nuclear protein , chemistry , gene expression , ubiquitin , biochemistry , retinoic acid , linguistics , philosophy
The transcription factor Nrf2 (nuclear factor erythroid 2‐related factor 2) induces transcription of a variety of genes by binding to the antioxidant response element(s) (ARE) in target gene promoters. Covalent modification(s) that may impact the biology of Nrf2 after its separation from its inhibitor protein Keap1 are not well‐delineated. Using reporter gene assays and fluorescence imaging in HepG2 cells, we have explored the role of sumoylation in the biological action of Nrf2. In the presence of the SUMO‐specific protease SENP‐1, Nrf2‐induced transcription from ARE‐driven reporter gene constructs was greatly enhanced, suggesting that sumoylation inhibits Nrf2‐induced gene transcription. Treatment with the proteasome inhibitor MG‐132 directed green fluorescent protein‐Nrf2 (GFP‐Nrf2) to promyelocytic leukemia nuclear bodies (PML‐NBs); this treatment also induced co‐localization of GFP‐Nrf2 with red fluorescent protein‐SUMO‐1 (RFP‐SUMO‐1). This localization was abrogated by co‐transfection with an expression plasmid for SENP‐1. We interpret these results to mean that Nrf2 traffics to PML‐NBs in a SUMO‐dependent manner. The results also implicate sumoylation in the transcriptional action of Nrf2. Supported by NIH grants # SC1CA143985 and T32HL007737