Nrf2 and oxidative stress-induced gene expression - Homo sapiens (human)

Curator(s): Peter D'Adamo

One of the rational and effective strategies for chemoprevention is the blockade of DNA damage caused by carcinogenic insult. This can be achieved either by reducing the formation of reactive carcinogenic species or stimulating their detoxification. A wide spectrum of xenobiotic metabolizing enzymes catalyze both phase I (oxidation and reduction) and phase II biotransformation (conjugation) reactions involved in carcinogen activation and/or deactivation. Several antioxidant-response element (ARE)-regulated gene products such as glutathione S-transferase, NAD(P)H:quinone oxidoreductase 1, UDP-glucuronosyltransferase, gamma-glutamate cysteine ligase, and hemeoxygenase-1 are known to mediate detoxification and/or to exert antioxidant functions thereby protecting cells from genotoxic damage. Nuclear factor (erythroid-derived 2)-like 2, also known as NFE2L2 or Nrf2, is a transcription factor that in humans is encoded by the NFE2L2 gene. NFE2L2 induces the expression of various genes including those that encode for several antioxidant enzymes, and it may play a physiological role in the regulation of oxidative stress. Investigational drugs that target NFE2L2 are of interest as potential therapeutic interventions for oxidative-stress related pathologies.    
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Nrf2 and oxidative stress-induced gene expression - Homo sapiens (human) cluster_NUCLEUS NUCLEUS node1 Reactive Oxygen Species (ROS) protein kinase C,alpha PRKCA node1->PRKCA ERK2 node1->ERK2 JNK1 node1->JNK1 p38 node1->p38 node2 4 PRKCA->node2 PRKCA P PRKCA->P node3 16 ERK2->node3 ERK2 ERK2->P node12 CREB1 JUN ATF4 FOS ERK2->node12 node4 11 node5 Nrf2 KEAP1 RBX1 CUL3 node5->node4 Nrf2~KEAP1~RBX1~CUL3 Q node5->Q P->Q node6 3 JNK1->P JNK1->node6 JNK1 JNK1->node12 node7 2 p38->P p38->node7 p38 p38->node12 node9 Nrf2 (1) Q->node9 +p kelch-like ECH-associated protein 1 KEAP1 Q->KEAP1 node8 10 node9->node8 Nrf2 (1) node11 Nrf2 (2) node9->node11 node10 10 node14 Detoxification/ ROS Breakdown node15 3 node16 node16->node14 node17 node17->node14 node18 node18->node14 node19 1 node20 node20->node14 node20->node19 node21 4 node22 node22->node14 node22->node21 node23 node23->node14 node24 2 node25 node25->node14 node25->node24 node27 1 KEAP1->node27 KEAP1 aldo-keto reductase family 7,member A2 (aflatoxin aldehyde reductase) AKR7A2 AKR7A2->node17 node13 ARE NFE2L2 bZIP node13->node18 node13->node20 node13->AKR7A2 glutamate-cysteine ligase,catalytic subunit GCLC node13->GCLC glutathione S-transferase alpha 2 GSTA2 node13->GSTA2 P450 (cytochrome) oxidoreductase POR node13->POR UDP glucuronosyltransferase 1 family,polypeptide A6 UGT1A6 node13->UGT1A6 GCLC->node25 GSTA2->node22 POR->node23 UGT1A6->node15 UGT1A6 UGT1A6->node16 node12->node13 node26 MAFK MAFF MAFG node26->node13 node11->node10 Nrf2 (2) node11->node13 print "