RGD Reference Report - The Nrf2 regulatory network provides an interface between redox and intermediary metabolism. - Rat Genome Database
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The Nrf2 regulatory network provides an interface between redox and intermediary metabolism.

Authors: Hayes, JD  Dinkova-Kostova, AT 
Citation: Hayes JD and Dinkova-Kostova AT, Trends Biochem Sci. 2014 Apr;39(4):199-218. doi: 10.1016/j.tibs.2014.02.002. Epub 2014 Mar 16.
RGD ID: 11535066
Pubmed: (View Article at PubMed) PMID:24647116
DOI: Full-text: DOI:10.1016/j.tibs.2014.02.002

Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2, also called Nfe2l2) is a transcription factor that regulates the cellular redox status. Nrf2 is controlled through a complex transcriptional/epigenetic and post-translational network that ensures its activity increases during redox perturbation, inflammation, growth factor stimulation and nutrient/energy fluxes, thereby enabling the factor to orchestrate adaptive responses to diverse forms of stress. Besides mediating stress-stimulated induction of antioxidant and detoxification genes, Nrf2 contributes to adaptation by upregulating the repair and degradation of damaged macromolecules, and by modulating intermediary metabolism. In the latter case, Nrf2 inhibits lipogenesis, supports beta-oxidation of fatty acids, facilitates flux through the pentose phosphate pathway, and increases NADPH regeneration and purine biosynthesis; these observations suggest Nrf2 directs metabolic reprogramming during stress.

Annotation

Molecular Pathway Annotations    
Objects Annotated

Genes (Rattus norvegicus)
Brca1  (BRCA1, DNA repair associated)
Btrc  (beta-transducin repeat containing E3 ubiquitin protein ligase)
Cdkn1a  (cyclin-dependent kinase inhibitor 1A)
Chd6  (chromodomain helicase DNA binding protein 6)
Crebbp  (CREB binding protein)
Cul1  (cullin 1)
Cul3  (cullin 3)
Dpp3  (dipeptidylpeptidase 3)
Gadd45gip1  (GADD45G interacting protein 1)
Ikbkb  (inhibitor of nuclear factor kappa B kinase subunit beta)
Keap1  (Kelch-like ECH-associated protein 1)
Maff  (MAF bZIP transcription factor F)
Mafg  (MAF bZIP transcription factor G)
Mafk  (MAF bZIP transcription factor K)
Ncoa3  (nuclear receptor coactivator 3)
Nfe2l2  (nuclear factor, erythroid 2-like 2)
Palb2  (partner and localizer of BRCA2)
Pgam5  (PGAM family member 5, mitochondrial serine/threonine protein phosphatase)
Rbx1  (ring-box 1)
Rnf4  (ring finger protein 4)
Siah2  (siah E3 ubiquitin protein ligase 2)
Skp1  (S-phase kinase-associated protein 1)
Sqstm1  (sequestosome 1)

Genes (Mus musculus)
Brca1  (breast cancer 1, early onset)
Btrc  (beta-transducin repeat containing protein)
Cdkn1a  (cyclin-dependent kinase inhibitor 1A (P21))
Chd6  (chromodomain helicase DNA binding protein 6)
Crebbp  (CREB binding protein)
Cul1  (cullin 1)
Cul3  (cullin 3)
Dpp3  (dipeptidylpeptidase 3)
Gadd45gip1  (growth arrest and DNA-damage-inducible, gamma interacting protein 1)
Ikbkb  (inhibitor of kappaB kinase beta)
Keap1  (kelch-like ECH-associated protein 1)
Maff  (v-maf musculoaponeurotic fibrosarcoma oncogene family, protein F (avian))
Mafg  (v-maf musculoaponeurotic fibrosarcoma oncogene family, protein G (avian))
Mafk  (v-maf musculoaponeurotic fibrosarcoma oncogene family, protein K (avian))
Ncoa3  (nuclear receptor coactivator 3)
Nfe2l2  (nuclear factor, erythroid derived 2, like 2)
Palb2  (partner and localizer of BRCA2)
Pgam5  (phosphoglycerate mutase family member 5)
Rbx1  (ring-box 1)
Rnf4  (ring finger protein 4)
Siah2  (siah E3 ubiquitin protein ligase 2)
Skp1  (S-phase kinase-associated protein 1)
Sqstm1  (sequestosome 1)

Genes (Homo sapiens)
BRCA1  (BRCA1 DNA repair associated)
BTRC  (beta-transducin repeat containing E3 ubiquitin protein ligase)
CDKN1A  (cyclin dependent kinase inhibitor 1A)
CHD6  (chromodomain helicase DNA binding protein 6)
CREBBP  (CREB binding protein)
CUL1  (cullin 1)
CUL3  (cullin 3)
DPP3  (dipeptidyl peptidase 3)
GADD45GIP1  (GADD45G interacting protein 1)
IKBKB  (inhibitor of nuclear factor kappa B kinase subunit beta)
KEAP1  (kelch like ECH associated protein 1)
MAFF  (MAF bZIP transcription factor F)
MAFG  (MAF bZIP transcription factor G)
MAFK  (MAF bZIP transcription factor K)
NCOA3  (nuclear receptor coactivator 3)
NFE2L2  (nuclear factor, erythroid 2 like 2)
PALB2  (partner and localizer of BRCA2)
PGAM5  (PGAM family member 5, mitochondrial serine/threonine protein phosphatase)
RBX1  (ring-box 1)
RNF4  (ring finger protein 4)
SIAH2  (siah E3 ubiquitin protein ligase 2)
SKP1  (S-phase kinase associated protein 1)
SQSTM1  (sequestosome 1)


Additional Information