RGD Reference Report - The Fbw7 tumor suppressor regulates nuclear factor E2-related factor 1 transcription factor turnover through proteasome-mediated proteolysis. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

The Fbw7 tumor suppressor regulates nuclear factor E2-related factor 1 transcription factor turnover through proteasome-mediated proteolysis.

Authors: Biswas, Madhurima  Phan, Diane  Watanabe, Momoko  Chan, Jefferson Y 
Citation: Biswas M, etal., J Biol Chem. 2011 Nov 11;286(45):39282-9. doi: 10.1074/jbc.M111.253807. Epub 2011 Sep 27.
RGD ID: 13464262
Pubmed: PMID:21953459   (View Abstract at PubMed)
PMCID: PMC3234752   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M111.253807   (Journal Full-text)

Nuclear factor E2-related factor 1 (Nrf1) is a basic leucine zipper transcription factor that plays important roles in cellular stress response and development. Currently, the mechanism regulating Nrf1 expression is poorly understood. We report here that Nrf1 is a short-lived protein that is targeted by F-box protein Fbw7, which is the substrate-specifying component of SCF (Skp1-Cul1-Fbox protein-Rbx1)-type ubiquitin ligase for degradation via the ubiquitin-proteasome pathway. We show that Fbw7 directly binds Nrf1 through a Cdc4 phosphodegron and that enforced expression of Fbw7 promotes the ubiquitination and degradation of Nrf1. Conversely, depletion of endogenous Fbw7 leads to decreased Nrf1 ubiquitination and accumulation of Nrf1 protein. Accordingly, expression of Fbw7 leads to down-regulation of antioxidant response element-driven gene activation, whereas disruption of Fbw7-mediated destabilization of Nrf1 leads to increased antioxidant response element-driven gene expression. Together, these data identify Fbw7 as a regulator of Nrf1 expression and reveal a novel function of Fbw7 in cellular stress response.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Fbxw7RatSCF-dependent proteasomal ubiquitin-dependent protein catabolic process involved_inISSUniProtKB:Q8VBV4PMID:21953459UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Fbxw7  (F-box and WD repeat domain containing 7)


Additional Information