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- Table of Contents
3 Citations
Facts about Kelch-like ECH-associated protein 1.
Targets PGAM5 for ubiquitination and degradation by the proteasome. .
Human | |
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Gene Name: | KEAP1 |
Uniprot: | Q14145 |
Entrez: | 9817 |
Belongs to: |
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KEAP1 family |
INrf2; INrf2MGC9454; Keap1; kelch-like ECH-associated protein 1; Kelch-like protein 19; KIAA0132MGC4407; KLHL19Cytosolic inhibitor of Nrf2; MGC10630; MGC1114; MGC20887
Mass (kDA):
69.666 kDA
Human | |
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Location: | 19p13.2 |
Sequence: | 19; NC_000019.10 (10486125..10503356, complement) |
Broadly expressed, with highest levels in skeletal muscle.
Cytoplasm. Nucleus. Mainly cytoplasmic (PubMed:15601839). In response to selective autophagy, relocalizes to inclusion bodies following interaction with SQSTM1/p62 (PubMed:20452972).
In this article, you'll learn why KEAP1 is a negative regulator of Nrf2 and why PPI inhibitors disrupt this interaction. It's also important to know the benefits of using Boster Bio's KEAP1 Marker. These tips will help you optimize your experiments and improve your results. While every experiment runs into problems, proper controls can help eliminate many causes of error. A Boster Bio troubleshooting guide will help you identify potential problems and solve them.
KEAP1 is a negative regulator in Boster Bio, where it controls the activity of Nrf2 in a variety of cellular situations. It is found to be expressed at increased levels in PBC and is omnipresent in the various cellular compartments. This protein is an important regulator of the Nrf2/Keap1 pathway, as it inhibits Nrf2 activity and acts as a postinduction repressor of Nrf2.
Nrf2-KEAP1 activity is necessary for proper cell functioning and redox homeostasis. By suppressing the activity of Nrf2, cells are more resistant to oxidative and reductive stress, and are more sensitive to various treatments, including radiation therapy. Keap1 is located in the cytoplasm and interacts with Nrf2 and KEAP1.
Several recent studies have demonstrated that the actions of KEAP1 and Nrf2 are neuroprotective. In a mouse model of multiple sclerosis, KEAP1 inhibited the expression of genes targeted by Nrf2, thereby increasing cell viability. Moreover, phosphorylation of p62 at Ser351 increased Keap1's binding affinity, resulting in increased levels of Nrf2 protein in the nucleus.
The function of Keap1 is not clear, but it is thought to play a role in focal adhesions and cell-cell junctions. It has also been shown to be present in fibrotic areas, as well as in nodules. The research team did not observe nuclear Keap1 expression in the neutrophils. A study published in Nature Communications in 2013 confirmed that Keap1 is a key regulator of Nrf2.
Keap1 is a negative regulator of Nrf2. In the context of pancreatic cancer, it is thought to be an important marker for the disease. Keap1 expression correlates with better survival in squamous non-small-cell lung cancer and a poor prognosis in triple-negative breast cancer. However, this protective role of Keap1 may not be as obvious as that of Nrf2, a positive regulator of Nrf2.
KEAP1 is a critical component of the Nrf2/Keap1 system in cellular redox homeostasis. KEAP1 destabilizes Keap1, which subsequently leads to accumulation of Nrf2. Eventually, Nrf2 accumulates in the nucleus, targeting the cis-acting antioxidant response element (CAR) to activate a set of genes. MicroRNAs and epigenetic mechanisms control the Nrf2/Keap1 signalling axis.
The expression of Nrf2 is highly elevated in PBC tissues. However, it is not elevated in tissues of patients with early PBC. However, the circulating redox balance is impaired in the early stages of the disease, which suggests that Nrf2 should be activated at an early stage. Furthermore, KEAP1 inactivates Nrf2 through binding to p62. Using this gene as a therapeutic target, this study investigated the Nrf2/KEAP1 axis in PBC patients.
KEAP1 is a negative regulator in Boster Bio. It requires two key amino acid sequences to bind Keap1 in Boster Bio. The sequences ETGE and DLG are essential for Keap1 to bind to Nrf2.
Among the potential targets of a novel chemotherapeutic, Keap1-Nrf2 PPI inhibitor, CPUY192018 inhibits the KEAP1-Nrf2 marker interaction. These inhibitors display cytoprotective effects in both mouse and NCM460 cells. They are potent in increasing Nrf2 signaling in intestinal cells. The intestinal epithelium is constantly exposed to diverse stressors and, as a result, becomes prone to oxidative damage. However, the Nrf2-ARE signaling pathway acts as a counteract to oxidative injury by preventing the cellular damage that is caused by oxidative stress.
Several classes of PPI inhibitors inhibit KEAP1-NRF2 interaction. The KEAP1-NRF2 PPI inhibitors interfere with direct interaction between KEAP1 and NRF2, and with KEAP1 and CUL3 as well. These inhibitors target the DEETGE motif of KEAP1 in the NRF2 binding pocket. The amino acid sequence DEETGE is essential for the interaction between NRF2 and KEAP1. It is fused to the Tat motif in human immunodeficiency virus and to the cleavage motif in calpain.
Inhibitors of KEAP1 inhibit the redox-regulated substrate adaptor protein NRF2. NRF2 acts as an essential regulator of cell proliferation and cell cycle arrest. However, when inhibited, KEAP1 reduces the ability of the nucleus to sequester de novo synthesized NRF2.
This study reveals that a mutation in the p62 functional domain is responsible for ALS and frontotemporal dementia. The mutation blocks KEAP1 from binding to NRF2 and prevents the NRF2 protein from entering the nucleus. These mutations result in decreased KEAP1-NRF2 interaction, which promotes apoptosis response and predisposition to cell death in response to ROS exposure.
In addition, the increased OS markers in the brain and peripheral tissues indicates a disorder of antioxidant defense and an imbalance between antioxidant defense. Understanding these changes could lead to novel therapeutic approaches for ALS. Furthermore, the PPI inhibitors disrupt the KEAP1 marker interaction and thereby inhibit the formation of apoptosis-associated proteins. These findings also indicate that KEAP1 inhibitors can block the activity of NRF2 in a number of cancer cell models.
However, KEAP1-NRF2 interactions are negatively regulated by several other factors. One of these is GSK-3b, a Ser/Thr protein kinase, which has been implicated in several metabolic processes, including glycogen metabolism and insulin signalling. By targeting these miRNAs, these inhibitors prevent KEAP1-NRF2 interaction. The inhibitors have also been associated with increased levels of reduced GSH in a number of cancer cell lines.
The benefits of using Boster's KEAP1, a marker for the KEAP1 protein, are numerous. For example, this marker can detect inflammatory kidney disease or toxic AVMs. In addition, Keap1 redistribution is a useful diagnostic tool for detecting IBM. Here are some of the main advantages of using Boster's KEAP1 marker:
NRF2 is a known cancer growth factor. Inhibition of NRF2 inhibits this receptor. However, safety and selectivity concerns remain. Moreover, cysteine is a ubiquitous constituent of human cells. Therefore, it is important to use Boster's KEAP1 marker in clinical research. Although this peptide can be detected in cancer cells, there are still many challenges that need to be overcome.
PMID: 14585973 by Zhang D.D., et al. Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress.
PMID: 15379550 by Strachan G.D., et al. Fetal Alz-50 clone 1 interacts with the human orthologue of the Kelch-like Ech-associated protein.
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