RGD Reference Report - The carboxy-terminal Neh3 domain of Nrf2 is required for transcriptional activation. - Rat Genome Database

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The carboxy-terminal Neh3 domain of Nrf2 is required for transcriptional activation.

Authors: Nioi, P  Nguyen, T  Sherratt, PJ  Pickett, CB 
Citation: Nioi P, etal., Mol Cell Biol. 2005 Dec;25(24):10895-906.
RGD ID: 8655528
Pubmed: PMID:16314513   (View Abstract at PubMed)
PMCID: PMC1316965   (View Article at PubMed Central)
DOI: DOI:10.1128/MCB.25.24.10895-10906.2005   (Journal Full-text)

Nrf2 is a transcription factor critical for the maintenance of cellular redox homeostasis. We have previously found that Nrf2 is a labile protein, and its activation in cells under stress involves mechanisms leading to its stabilization. As a modular protein, Nrf2 possesses distinct transactivation and DNA binding domains essential for its transcriptional activity. In this study, we found that the C-terminal "Neh3" domain of Nrf2 is also important for its activity. Deletion of the last 16 amino acids of the protein completely abolishes its ability to activate both reporter and endogenous gene expression. Using site-directed mutagenesis, we have identified a stretch of amino acids within this region that are essential for its activity and that are found to be conserved across species and among other members of the CNC-bZIP family. Importantly, deletion of the final 16 amino acids of Nrf2 does not influence its dimerizing capability, DNA binding activity, or subcellular localization, although it does increase the half-life of the protein. In addition, this region was found to be important for interaction with CHD6 (a chromo-ATPase/helicase DNA binding protein) in a yeast two-hybrid screen. RNA interference-mediated knockdown of CHD6 reduced both the basal and tert-butylhydroquinone-inducible expression of NQO1, a prototypical Nrf2 target gene. These data suggest that the Neh3 domain may act as a transactivation domain and that it is possibly involved in interaction with components of the transcriptional apparatus to affect its transcriptional activity.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cell redox homeostasis involved_inIMP 8655528PMID:16314513UniProt 
positive regulation of transcription by RNA polymerase II involved_inIMP 8655528PMID:16314513UniProt 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
nucleus located_inIDA 8655528PMID:16314513UniProt 

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Nfe2l2  (NFE2 like bZIP transcription factor 2)

Objects referenced in this article
Gene Mafk MAF bZIP transcription factor K Rattus norvegicus

Additional Information