Mouse Kelch-like ECH-associated protein 1(KEAP1) ELISA kit

Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that regulates the response to oxidative stress by targeting NFE2L2/NRF2 for ubiquitination. KEAP1 acts as a key sensor of oxidative and electrophilic stress: in normal conditions, the BCR(KEAP1) complex mediates ubiquitination and degradation of NFE2L2/NRF2, a transcription factor regulating expression of many cytoprotective genes. In response to oxidative stress, different electrophile metabolites trigger non-enzymatic covalent modifications of highly reactive cysteine residues in KEAP1, leading to inactivate the ubiquitin ligase activity of the BCR(KEAP1) complex, promoting NFE2L2/NRF2 nuclear accumulation and expression of phase II detoxifying enzymes. In response to selective autophagy, KEAP1 is sequestered in inclusion bodies following its interaction with SQSTM1/p62, leading to inactivation of the BCR(KEAP1) complex and activation of NFE2L2/NRF2. The BCR(KEAP1) complex also mediates ubiquitination of SQSTM1/p62, increasing SQSTM1/p62 sequestering activity and degradation. The BCR(KEAP1) complex also targets BPTF and PGAM5 for ubiquitination and degradation by the proteasome.

1. Nrf2/Keap1 system regulates VSMC apoptosis during neointimal formation, thereby inhibiting neointimal hyperplasia after a vascular injury. PMID: 27198574
2. Renal tubular deletion of Keap1 promotes nephrogenic diabetes insipidus features, confirming that Nrf2 activation in developing tubular cells causes a water reabsorption defect. PMID: 28233855
3. By inhibiting binding of Keap1 to Nrf2. PMID: 30021365
4. these studies are the first to demonstrate that Brain ischemic preconditioning protects the blood-brain barrier against ischemic injury by generation of endogenous electrophiles and activation of the Nrf2 pathway through inhibition of Keap1- and GSK3beta-dependent Nrf2 degradation. PMID: 29775963
5. these results suggested that trehalose can function as a novel activator of the p62-Keap1/Nrf2 pathway, in addition to inducing autophagy. Therefore, trehalose may be useful to treat many chronic diseases involving oxidative stress and dysfunction of autophagy. PMID: 29241092
6. While injury tended to suppress these genes in wild-type mice, the suppression was attenuated or reversed in Keap1 hypomorphs, suggesting that protection in these mice was mediated by increased Nrf2 transcriptional activity. PMID: 27804998
7. These findings suggest that Keap1-Nrf2 system plays a key role in depression and that dietary intake of sulforaphane-rich food during juvenile stages and adolescence can confer stress resilience in adulthood. PMID: 27470577
8. these results indicated that inactivation of KEAP1 protein by epigallocatechin gallate may mediate epigallocatechin gallate function in activating NRF2 PMID: 28457936
9. the incidence, multiplicity and burden of Cutaneous squamous cell carcinomas that form in Keap1(flox/flox)/Nrf2(-/-) mice are much greater than in their Keap1(flox/flox)/Nrf2(+/+) counterparts, establishing Nrf2 activation as the protection mediator. PMID: 27216826
10. The p62-keap1-Nrf2 antioxidant pathway was primarily activated in the early stage of APAP hepatotoxicity. PMID: 29331651
11. Keap1 deletion in renal tubular cells results in an abnormal kidney development consistent with hydronephrosis. PMID: 27484495
12. serine 351 phosphorylation of p62 did not enhance its binding to Keap1 or stabilise the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor in this neuronal context. Nrf2 protein levels were markedly decreased despite transcriptional activation of the Nrf2 gene PMID: 28055010
13. These results suggest that the Keap1/Nrf2 axis plays a critical role in NFATc1 expression and osteoclastogenic progression. PMID: 28515152
14. Results show that Keap1 deficiency in long-term hematopoietic stem cells increases the number of multipotent progenitor cells in steady-state hematopoiesis, and impairs their hematopoietic regeneration capacity . PMID: 28674188
15. During cellular stress or electrolytic imbalance, cysteine residue modification in Keap1 induces Nrf2 release from the Nrf2-Keap1 complex, which stabilizes Nrf2 and causes its nuclear translocation. PMID: 28045693
16. This study found that under oxidative stress induced by experimental periodontitis, the Nrf2/antioxidant defense pathway was activated and could be visualized from the luciferase activity in the in Keap1-dependent oxidative stress detector-luciferase mice model. PMID: 27854327
17. Caffeic acid induces Nrf2 activation by decreasing the expression of its inhibitor protein Keap1 and blocking the binding of Nrf2 with Keap1. PMID: 26721592
18. Hepatocyte-specific deletion of Keap1 triggering constitutive Nrf2 activation shifts hepatic metabolism towards increased lipid catabolism, reduced liponeogenesis and activation of the pentose phosphate pathway. PMID: 26698665
19. findings reveal that Keap1 regulates cell migration by affecting the subcellular localization and activity of cortactin independently of its role in oxidant stress responses. PMID: 26602019
20. chronic hyperglycemic conditions, Keap1 inhibition increased Nrf2 nuclear translocation, increased antioxidant gene expression, and reduced ROS production to normoglycemic levels. PMID: 26647385
21. conclusion, increased Keap1/Nrf2 signaling in the liver is accompanied by repressed gluconeogenesis and lipogenesis that can, at least partially, explain the ameliorated diabetic phenotype in the Keap1-hypo mice. PMID: 26701603
22. Keap1 utilizes multiple cysteine residues specifically and/or collaboratively as sensors for the detection of a wide range of environmental stresses. PMID: 26527616
23. iron deficiency induced the nuclear translocation of Nrf2 via Keap1 degradation by autophagy and subsequently upregulated expression of HO-1. PMID: 25754743
24. These results strongly suggest that p62 plays a crucial role in preventing fenofibrate-induced cell death. PMID: 26282199
25. high-fat diet altered short-term glucose homeostasis to a greater degree in Keap-KD mice compared to C57BL/6 mice PMID: 23507082
26. Keap1 knockdown caused severe disruption in both the redox cycle and the cell cycle of replicating hepatocytes. PMID: 25483186
27. data confirm a role for GNOM in endoplasmic reticulum (ER)-Golgi trafficking and reveal that a GNL1/GNOM-mediated early secretory pathway selectively regulates PIN1 basal polarity establishment in a manner essential for normal plant development PMID: 24997191
28. Results implicate p62-dependent autophagic degradation of Keap1 by palmitate as a mechanism contributing to hepatocyte lipoapoptosis. PMID: 24769730
29. the high degree of selectivity of CDDO-me for the Nrf2:Keap1 signalling pathway. PMID: 24859727
30. Data indicate feedback activation of the kelch-like ECH-associated protein 1 (Keap1)-NF-E2-Related Factor 2 (Nrf2) pathway when the proteasome is impaired. PMID: 25049227
31. forced expression of WT mKeap1 restored the ability of oxaliplatin to activate the transcription factor. Cys(151) in Keap1 was required for the response stimulated by oxaliplatin. PMID: 24556415
32. Nrf2 activation by Keap1 knockdown attenuates glomerulosclerosis. These results indicate that the Nrf2-Keap1 system is a promising drug target for the treatment of chronic kidney diseases. PMID: 24523358
33. Keap1-Nrf2 complex prevents oxidative injury in ischemia/reperfusion-stressed orthotopic liver transplantation through Keap1 signaling, which negatively regulates Nrf2 pathway. PMID: 23867319
34. The bone marrow cells of Keap1-deficient mice showed enhanced granulocyte-monocyte differentiation and lower erythroid and lymphoid, suggesting granulocyte-monocyte lineage priming in Keap1-null HSCs. PMID: 24580727
35. Caloric restriction induced induction of fatty acid oxidation gene expression was augmented with Keap1 knockdown, which was associated with differential expression of several miRNAs implicated in fatty acid oxidation and lipid accumulation. PMID: 23884569
36. Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective autophagy. PMID: 24011591
37. Silencing of Keap1 in macrophages boosts induced transcription of Il-6 via NF-kappaB activation. PMID: 23906629
38. the Keap1/Nrf2 axis regulates RANKL-dependent osteoclastogenesis through modulation of intracellular ROS signaling via expression of cytoprotective enzymes. PMID: 23801334
39. Genetic activation of Nrf2 signaling by Keap1 gene hypomorphic knockdown (Keap1flox/-) markedly suppresses the onset of diabetes. PMID: 23716596
40. This study assigns a novel positive role of Keap1 in upregulating p62-mediated autophagic clearance of ubiquitin aggregates. PMID: 20495340
41. R-alpha-lipoic acid exerts a neuroprotective effect against oxidative stress in retinal neurons in vitro and in vivo by inducing HO-1 through Keap1/Nrf2 signaling. PMID: 23295186
42. the Keap1-C151-dependent mechanism of Nrf2 activation is protective, while p62-mediated activation or somatic mutations leading to persistent or prolonged Nrf2 activation comprise the side of Nrf2 that is expected to promote tumor growth and survival. PMID: 23589329
43. The Keap1-Nrf2 system regulates an important defense mechanism against upper aerodigestive tract carcinogenesis. PMID: 23250896
44. study discovered that the Nrf2/Keap1 pathway detects loss of loricrin and directly upregulates the expression of genes involved in the compensatory response, thus ensuring postnatal survival PMID: 23237955
45. HFD-induced obesity and lipid accumulation in white adipose tissue was decreased in Keap1-KD mice PMID: 22936178
46. The autophagy pathway maintains the integrity of the Keap1-Nrf2 system for the normal liver function by governing the Keap1 turnover PMID: 22872865
47. Morphological changes of the esophageal epithelium are associated with dynamic changes in gene expression. Nrf2/Keap1 pathway activity is required for maturation of mouse esophageal epithelium. PMID: 22567161
48. Activation of endogenous intracellular levels of Nrf2 by siRNA knockdown of Keap1 is sufficient to protect in models of oxidative stress and Parkinson's disease. PMID: 22342405
49. The p62-Nrf2-Nqo1 cascade functions to assure mammalian longevity by stabilizing mitochondrial integrity. PMID: 22222206
50. Induction of antioxidative stress protein keap1 after cerebral ischemia may play an important endogenous neuroprotective response. PMID: 21075092

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Cytoplasm. Nucleus.

KEGG: mmu:50868

STRING: 10090.ENSMUSP00000062467

UniGene: Mm.248266