This recombinant mouse Keap1 protein is tagged with an N-terminal 6xHis-SUMO. It is generated by expressing the vector that contains the gene fragment encoding the 1-624aa of mouse Keap1 and the N-terminal 6xHis-SUMO-tag gene in E.coli. Its purity reaches over 90% as determined by SDS-PAGE. It is recommended for Keap1-associated epigenetics and nuclear signaling research.
Keap1 is a critical regulator of the Nrf2 signaling pathway, which plays a vital role in cellular defense against oxidative stress and inflammation. Under normal physiological conditions, Keap1 is an adaptor protein that binds to Nrf2 in the cytoplasm, facilitating its ubiquitination and subsequent proteasomal degradation. This process maintains low levels of Nrf2, thereby preventing excessive activation of antioxidant responses [1][2][3]. However, under oxidative stress, Keap1 undergoes conformational changes due to the modification of its cysteine residues, leading to the release of Nrf2. This release allows Nrf2 to translocate to the nucleus, where it activates the transcription of various antioxidant genes, including heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1) [4][5][6].
The Keap1-Nrf2 pathway is particularly significant in the context of various diseases, including diabetic kidney disease and cancer. Research has also indicated that Keap1 participates in multiple cellular processes, including autophagy and lipid metabolism [7][8].
References:
[1] J. Dong, Microrna-204-5p ameliorates renal injury via regulating keap1/nrf2 pathway in diabetic kidney disease, Diabetes Metabolic Syndrome and Obesity Targets and Therapy, vol. Volume 17, p. 75-92, 2024. https://doi.org/10.2147/dmso.s441082
[2] P. Ren, F. Qian, L. Fu, W. He, Q. He, J. Jinet al., Adipose-derived stem cell exosomes regulate nrf2/keap1 in diabetic nephropathy by targeting fam129b, Diabetology & Metabolic Syndrome, vol. 15, no. 1, 2023. https://doi.org/10.1186/s13098-023-01119-5
[3] K. Wu, J. Cui, & C. Klaassen, Beneficial role of nrf2 in regulating nadph generation and consumption, Toxicological Sciences, vol. 123, no. 2, p. 590-600, 2011. https://doi.org/10.1093/toxsci/kfr183
[4] P. Klemm, A. Rajendiran, A. Fragoulis, C. Wruck, A. Schippers, N. Wagneret al., Nrf2 expression driven by foxp3 specific deletion of keap1 results in loss of immune tolerance in mice, European Journal of Immunology, vol. 50, no. 4, p. 515-524, 2020. https://doi.org/10.1002/eji.201948285
[5] Y. Sogawa, H. Nagasu, S. Iwase, C. Ihoriya, S. Itano, A. Uchidaet al., Infiltration of m1, but not m2, macrophages is impaired after unilateral ureter obstruction in nrf2-deficient mice, Scientific Reports, vol. 7, no. 1, 2017. https://doi.org/10.1038/s41598-017-08054-2
[6] M. Nezu, T. Souma, L. Yu, T. Suzuki, D. Saigusa, S. Itoet al., Transcription factor nrf2 hyperactivation in early-phase renal ischemia-reperfusion injury prevents tubular damage progression, Kidney International, vol. 91, no. 2, p. 387-401, 2017. https://doi.org/10.1016/j.kint.2016.08.023
[7] K. Taguchi, N. Fujikawa, M. Komatsu, T. Ishii, M. Unno, T. Akaikeet al., Keap1 degradation by autophagy for the maintenance of redox homeostasis, Proceedings of the National Academy of Sciences, vol. 109, no. 34, p. 13561-13566, 2012. https://doi.org/10.1073/pnas.1121572109
[8] J. Xu, A. Donepudi, J. Moscovitz, & A. Slitt, Keap1-knockdown decreases fasting-induced fatty liver via altered lipid metabolism and decreased fatty acid mobilization from adipose tissue, Plos One, vol. 8, no. 11, p. e79841, 2013. https://doi.org/10.1371/journal.pone.0079841
