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Sumoylation of the transcription factor Nrf2 (739.3)
Author(s) -
Walters Treniqka,
Arinze Ifeanyi
Publication year - 2014
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.28.1_supplement.739.3
Subject(s) - sumo protein , transcription factor , keap1 , promoter , sumo enzymes , microbiology and biotechnology , transcription (linguistics) , biology , chemistry , gene , genetics , gene expression , ubiquitin , linguistics , philosophy
The transcription factor Nrf2 induces transcription by binding to the antioxidant response element(s) in target gene promoters, enabling oxidatively stressed cells to mount a response to oxidative stress in order to restore redox homeostasis. To act as a transcription factor, Nrf2 must be separated from its inhibitory protein Keap1. Post‐translational modifications (PTMs) that mediate separation of Nrf2 from Keap1 have been extensively studied but PTMs that impact its biology after this separation are just beginning to emerge. Using in vitro sumoylation assay and other methods, we demonstrated that Nrf2 is a SUMO‐targeted protein [Malloy et al. (2013) JBC 288, 14569‐14583]. Here, we have used three SUMO site‐predicting algorithms (SeeSUMO, SUMOsp and SUMOplot) to locate putative SUMO‐binding sites in mouse Nrf2. Three of the fifteen putative sumoylation sites identified by these algorithms have high probability scores on all three prediction algorithms. Using site‐directed mutagenesis, Co‐IP, and in vitro sumoylation assays, we investigated which of these sites is/are authentic for SUMO conjugation. We also assessed whether sumoylating Nrf2 impacts its transcriptional activity. Grant Funding Source : Supported by NIH grants SC1CA143985, 5T32 GM07628‐34 and CTSA award No.UL1TR000445 from the NCATS.