Table 2.
The interaction between Nrf2 and other signaling pathways.
| Pathways Interacting with Nrf2 | Inhibition/Stimulation Activity | Effect | Reference |
|---|---|---|---|
| Nuclear factor kappa light chain enhancer of activated B cells (NF-κB) | ↓ Nrf2 ↑ NF-κB | Enhanced Inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ) activity, degradation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) | [122] |
| ↑ Nrf2 ↑ Glutathione (GSH) ↓ p65 |
[123] | ||
| ↓ p65 ↑ Nrf2–CREB-binding protein (CBP) complex association |
Increased Nrf2 binding to CBP (cAMP response element-binding protein (CREB)-binding protein) | [115] | |
| Rac Family Small GTPase 1 (RAC1) → Nrf2 levels ↑ | Protective mechanism against the inflammation consequences | [124] | |
| Lipopolysaccharides (LPS) → Rac Family Small GTPase 1(RAC)1 → Nrf2-mediated Heme Oxygenase 1 (HO-1) ↑ | |||
| ↑ p62 ↑ Nrf2 | Modulation of antioxidant and inflammatory activities | [15] | |
| ↑ p62 ↑ Tumour Necrosis Factor α (TNFα) | |||
| Phosphoinositide 3-kinases (PI3K)/RAC-alpha serine/threonine-protein kinase (Akt) | ↓ Nrf2 ↓ Nicotinamide adenine dinucleotide phosphate (NAD(P)H) |
Proliferation of cancer cell lines with constitutive Nrf2 accumulation | [68,125,126] |
| ↑ PI3K ↑ Nrf2 | Pten deletion → Nrf2 function →antioxidant response elements (ARE)-driven gene expression by Nrf2 | ||
| ↑ PI3K/Akt ↑ Nrf2 | Modulation of the metabolic activity in the liver | ||
| ↑ PI3K/Akt ↑ Nrf2 | PI3K activation enhances the nuclear availability of Nrf2 | ||
| Notch 1 | ↑ Nrf2 ↑ Notch1 and Hes1 messenger RNA (mRNA) | Promotes proliferation, migration, invasion, cell cycle, and colony formation of Oral Squamous Cell Carcinoma (OSCC) cells | [120] |
| ↓ Nrf2 ↓ Notch1 and Hes1 mRNA | |||
| Wingless-Type MMTV Integration Site Family, Member 3A (WNT-3A) | ↑ Nrf2 ↑ WNT-3A ↑ HO-1 ↑ β-Catenin ↓ Axin1 |
Modulates hepatocyte metabolism | [127] |
| Kirsten Rat Sarcoma Viral Oncogene Homolog (K-Ras), v-Raf murine sarcoma viral oncogene homolog B (B-Raf), Myc | ↑ Nrf2 activity ↑ K-Ras |
Initiates pancreatic and lung tumorigenesis and proliferation | [128] |
| Proteosomal ubiquination | ↑ p62 ↑ Nrf2 | Kelch-like ECH-associated protein 1 (Keap1) inactivated; alterations of selective autophagy | [129] |
| B-Raf Proto-Oncogene, Serine/Threonine Kinase (MAPK) | ↑ p38 ↑ c-Jun N-terminal kinases (JNK) ↑ Nrf2 |
MEQ (mequindox) induced redox imbalance damage in the mouse liver | [130] |