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: PMID:24647116   (View Abstract at PubMed)
DOI: DOI:10.1016/j.tibs.2014.02.002   (Journal Full-text)

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.



Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BRCA1Humannuclear factor, erythroid 2 like 2 signaling pathway   TAS  RGD 
BTRCHumannuclear factor, erythroid 2 like 2 signaling pathway   TAS  RGD 
Brca1Ratnuclear factor, erythroid 2 like 2 signaling pathway   ISOBRCA1 (Homo sapiens) RGD 
Brca1Mousenuclear factor, erythroid 2 like 2 signaling pathway   ISOBRCA1 (Homo sapiens) RGD 
BtrcRatnuclear factor, erythroid 2 like 2 signaling pathway   ISOBTRC (Homo sapiens) RGD 
BtrcMousenuclear factor, erythroid 2 like 2 signaling pathway   ISOBTRC (Homo sapiens) RGD 
CDKN1AHumannuclear factor, erythroid 2 like 2 signaling pathway   TAS  RGD 
CHD6Humannuclear factor, erythroid 2 like 2 signaling pathway   TAS  RGD 
CREBBPHumannuclear factor, erythroid 2 like 2 signaling pathway   TAS  RGD 
CUL1Humannuclear factor, erythroid 2 like 2 signaling pathway   TAS  RGD 
CUL3Humannuclear factor, erythroid 2 like 2 signaling pathway   TAS  RGD 
Cdkn1aRatnuclear factor, erythroid 2 like 2 signaling pathway   ISOCDKN1A (Homo sapiens) RGD 
Cdkn1aMousenuclear factor, erythroid 2 like 2 signaling pathway   ISOCDKN1A (Homo sapiens) RGD 
Chd6Ratnuclear factor, erythroid 2 like 2 signaling pathway   ISOCHD6 (Homo sapiens) RGD 
Chd6Mousenuclear factor, erythroid 2 like 2 signaling pathway   ISOCHD6 (Homo sapiens) RGD 
CrebbpRatnuclear factor, erythroid 2 like 2 signaling pathway   ISOCREBBP (Homo sapiens) RGD 
CrebbpMousenuclear factor, erythroid 2 like 2 signaling pathway   ISOCREBBP (Homo sapiens) RGD 
Cul1Ratnuclear factor, erythroid 2 like 2 signaling pathway   ISOCUL1 (Homo sapiens) RGD 
Cul1Mousenuclear factor, erythroid 2 like 2 signaling pathway   ISOCUL1 (Homo sapiens) RGD 
Cul3Ratnuclear factor, erythroid 2 like 2 signaling pathway   ISOCUL3 (Homo sapiens) RGD 
Cul3Mousenuclear factor, erythroid 2 like 2 signaling pathway   ISOCUL3 (Homo sapiens) RGD 
DPP3Humannuclear factor, erythroid 2 like 2 signaling pathway   TAS  RGD 
Dpp3Ratnuclear factor, erythroid 2 like 2 signaling pathway   ISODPP3 (Homo sapiens) RGD 
Dpp3Mousenuclear factor, erythroid 2 like 2 signaling pathway   ISODPP3 (Homo sapiens) RGD 
GADD45GIP1Humannuclear factor, erythroid 2 like 2 signaling pathway   TAS  RGD 
Gadd45gip1Ratnuclear factor, erythroid 2 like 2 signaling pathway   ISOGADD45GIP1 (Homo sapiens) RGD 
Gadd45gip1Mousenuclear factor, erythroid 2 like 2 signaling pathway   ISOGADD45GIP1 (Homo sapiens) RGD 
IKBKBHumannuclear factor, erythroid 2 like 2 signaling pathway   TAS  RGD 
IkbkbRatnuclear factor, erythroid 2 like 2 signaling pathway   ISOIKBKB (Homo sapiens) RGD 
IkbkbMousenuclear factor, erythroid 2 like 2 signaling pathway   ISOIKBKB (Homo sapiens) RGD 
KEAP1Humannuclear factor, erythroid 2 like 2 signaling pathway   TAS  RGD 
Keap1Ratnuclear factor, erythroid 2 like 2 signaling pathway   ISOKEAP1 (Homo sapiens) RGD 
Keap1Mousenuclear factor, erythroid 2 like 2 signaling pathway   ISOKEAP1 (Homo sapiens) RGD 
MAFFHumannuclear factor, erythroid 2 like 2 signaling pathway   TAS  RGD 
MAFGHumannuclear factor, erythroid 2 like 2 signaling pathway   TAS  RGD 
MAFKHumannuclear factor, erythroid 2 like 2 signaling pathway   TAS  RGD 
MaffRatnuclear factor, erythroid 2 like 2 signaling pathway   ISOMAFF (Homo sapiens) RGD 
MaffMousenuclear factor, erythroid 2 like 2 signaling pathway   ISOMAFF (Homo sapiens) RGD 
MafgRatnuclear factor, erythroid 2 like 2 signaling pathway   ISOMAFG (Homo sapiens) RGD 
MafgMousenuclear factor, erythroid 2 like 2 signaling pathway   ISOMAFG (Homo sapiens) RGD 
MafkRatnuclear factor, erythroid 2 like 2 signaling pathway   ISOMAFK (Homo sapiens) RGD 
MafkMousenuclear factor, erythroid 2 like 2 signaling pathway   ISOMAFK (Homo sapiens) RGD 
NCOA3Humannuclear factor, erythroid 2 like 2 signaling pathway   TAS  RGD 
NFE2L2Humannuclear factor, erythroid 2 like 2 signaling pathway   TAS  RGD 
Ncoa3Ratnuclear factor, erythroid 2 like 2 signaling pathway   ISONCOA3 (Homo sapiens) RGD 
Ncoa3Mousenuclear factor, erythroid 2 like 2 signaling pathway   ISONCOA3 (Homo sapiens) RGD 
Nfe2l2Ratnuclear factor, erythroid 2 like 2 signaling pathway   ISONFE2L2 (Homo sapiens) RGD 
Nfe2l2Mousenuclear factor, erythroid 2 like 2 signaling pathway   ISONFE2L2 (Homo sapiens) RGD 
PALB2Humannuclear factor, erythroid 2 like 2 signaling pathway   TAS  RGD 
PGAM5Humannuclear factor, erythroid 2 like 2 signaling pathway   TAS  RGD 
Palb2Ratnuclear factor, erythroid 2 like 2 signaling pathway   ISOPALB2 (Homo sapiens) RGD 
Palb2Mousenuclear factor, erythroid 2 like 2 signaling pathway   ISOPALB2 (Homo sapiens) RGD 
Pgam5Ratnuclear factor, erythroid 2 like 2 signaling pathway   ISOPGAM5 (Homo sapiens) RGD 
Pgam5Mousenuclear factor, erythroid 2 like 2 signaling pathway   ISOPGAM5 (Homo sapiens) RGD 
RBX1Humannuclear factor, erythroid 2 like 2 signaling pathway   TAS  RGD 
RNF4Humannuclear factor, erythroid 2 like 2 signaling pathway   TAS  RGD 
Rbx1Ratnuclear factor, erythroid 2 like 2 signaling pathway   ISORBX1 (Homo sapiens) RGD 
Rbx1Mousenuclear factor, erythroid 2 like 2 signaling pathway   ISORBX1 (Homo sapiens) RGD 
Rnf4Ratnuclear factor, erythroid 2 like 2 signaling pathway   ISORNF4 (Homo sapiens) RGD 
Rnf4Mousenuclear factor, erythroid 2 like 2 signaling pathway   ISORNF4 (Homo sapiens) RGD 
SIAH2Humannuclear factor, erythroid 2 like 2 signaling pathway   TAS  RGD 
SKP1Humannuclear factor, erythroid 2 like 2 signaling pathway   TAS  RGD 
SQSTM1Humannuclear factor, erythroid 2 like 2 signaling pathway   TAS  RGD 
Siah2Ratnuclear factor, erythroid 2 like 2 signaling pathway   ISOSIAH2 (Homo sapiens) RGD 
Siah2Mousenuclear factor, erythroid 2 like 2 signaling pathway   ISOSIAH2 (Homo sapiens) RGD 
Skp1Ratnuclear factor, erythroid 2 like 2 signaling pathway   ISOSKP1 (Homo sapiens) RGD 
Skp1Mousenuclear factor, erythroid 2 like 2 signaling pathway   ISOSKP1 (Homo sapiens) RGD 
Sqstm1Ratnuclear factor, erythroid 2 like 2 signaling pathway   ISOSQSTM1 (Homo sapiens) RGD 
Sqstm1Mousenuclear factor, erythroid 2 like 2 signaling pathway   ISOSQSTM1 (Homo sapiens) RGD 
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  (NFE2 like bZIP transcription factor 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)
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  (NFE2 like bZIP transcription factor 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