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Human KEAP1 Protein expressed in HEK-293 Cells - ABIN2724103
Lieder, Reisen, Geppert, Sollberger, Beer, auf dem Keller, Schäfer, Detmar, Schneider, Werner: Identification of UV-protective activators of nuclear factor erythroid-derived 2-related factor 2 (Nrf2) by combining a chemical library screen with computer-based virtual screening. in The Journal of biological chemistry 2012
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Keap1 (Kelch-like ECH-associated protein 1) is an adaptor subunit of Cullin 3 (show CUL3 Proteins)-based E3 ubiquitin ligase (show MUL1 Proteins). Keap1 regulates the activity of Nrf2 (show GABPA Proteins) and acts as a sensor for oxidative and electrophilic stresses.
NRF2 (show GABPA Proteins) is regulated at protein level by proteasomal degradation via KEAP1. Data suggest that antioxidant-induced up-regulation of NRF2 (show GABPA Proteins) expression (a) overcomes KEAP1 regulation, (b) activates NRF2 (show GABPA Proteins) translocation to nucleus, and (c) activates antioxidant response element. (NRF2 (show GABPA Proteins) = nuclear factor [erythroid-derived 2]-like 2 protein; KEAP1 = Kelch-like ECH-associated protein 1)
Results indicate that microRNA miR (show MLXIP Proteins)-141 targets kelch like ECH associated protein 1 (Keap1) to activate NF-E2-related factor 2 (Nrf2 (show NFE2L2 Proteins)) signaling, which protects retinal pigment epithelium cells (RPEs) and retinal ganglion cells (RGCs) from UV radiation.
The authors show that O-GlcNAcylation of KEAP1 by OGT (show OGT Proteins) at serine 104 is required for the efficient ubiquitination and degradation of NRF2 (show GABPA Proteins).
Data indicate the role of kelch like ECH associated protein 1 (Keap1)/nuclear factor E2-related factor 2 (Nrf2 (show GABPA Proteins)) axis deregulation with potential new function as independent epigenetic prognostic marker in renal cell carcinoma (show MOK Proteins).
clinical cholangiocarcinoma samples displayed FoxO3 (show FOXO3 Proteins)-Keap1 down-regulation and Nrf2 (show GABPA Proteins) hyperactivation
the dual role of nuclear factor-erythroid 2 signaling in induction of colorectal cancer cell survival and death as well as the possibility of targeting nuclear factor-erythroid 2-kelch-like ECH-associated protein 1 axis as an advanced strategy in prevention and effective treatment of colorectal cancer patients have been discussed.
p97 (show EIF4G2 Proteins) negatively regulates NRF2 (show GABPA Proteins) through the canonical pathway by extracting ubiquitylated NRF2 (show GABPA Proteins) from the KEAP1-CUL3 (show CUL3 Proteins) E3 complex.
Using a combination of biochemical and mass spectrometry studies, the authors show that VP24 is a dimer in solution that directly binds to the Kelch domain of Kelch-like ECH-associated protein 1 (Keap1) to regulate nuclear factor (erythroid-derived 2)-like 2 (Nrf2 (show NFE2L2 Proteins)).
These data establish new functions for KEAP1 within the nucleus and identify MCM3 as a novel substrate of the KEAP1-CUL3-RBX1 E3 ligase.
the potency of 15d-PGJ2 as a signalling molecule (show GDF5 Proteins) in endothelial cells is significantly enhanced by the accumulation of the covalent adduct with 15d-PGJ2 and endogenous Keap1 over the time of exposure to the prostaglandin
These results suggest that the Keap1/Nrf2 (show NFE2L2 Proteins) axis plays a critical role in NFATc1 (show NFATC1 Proteins) expression and osteoclastogenic progression.
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 .
During cellular stress or electrolytic imbalance, cysteine residue modification in Keap1 induces Nrf2 (show NFE2L2 Proteins) release from the Nrf2 (show NFE2L2 Proteins)-Keap1 complex, which stabilizes Nrf2 (show NFE2L2 Proteins) and causes its nuclear translocation.
Results showed that in the basal state, the amount of Keap1 and Cul3 (show CUL3 Proteins) proteins were maintained at higher levels than that of Nrf2 (show NFE2L2 Proteins), and remained the same even under oxidative and electrophilic stimuli.
This study found that under oxidative stress induced (show SQSTM1 Proteins) by experimental periodontitis, the Nrf2 (show NFE2L2 Proteins)/antioxidant defense pathway was activated and could be visualized from the luciferase activity in the in Keap1-dependent oxidative stress detector-luciferase mice model.
Caffeic acid induces Nrf2 (show NFE2L2 Proteins) activation by decreasing the expression of its inhibitor protein Keap1 and blocking the binding of Nrf2 (show NFE2L2 Proteins) with Keap1.
Hepatocyte-specific deletion of Keap1 triggering constitutive Nrf2 (show NFE2L2 Proteins) activation shifts hepatic metabolism towards increased lipid catabolism, reduced liponeogenesis and activation of the pentose phosphate pathway.
findings reveal that Keap1 regulates cell migration by affecting the subcellular localization and activity of cortactin (show CTTN Proteins) independently of its role in oxidant stress responses.
chronic hyperglycemic conditions, Keap1 inhibition increased Nrf2 (show NFE2L2 Proteins) nuclear translocation, increased antioxidant gene expression, and reduced ROS (show ROS1 Proteins) production to normoglycemic levels.
conclusion, increased Keap1/Nrf2 (show NFE2L2 Proteins) 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.
mutation of either residual cysteine residue in Keap1a and Keap1b disrupted the ability of Keap1 to repress Nrf2 (show NFE2L2 Proteins), indicating that the presence of either Cys (show DNAJC5 Proteins)-273 or Cys (show DNAJC5 Proteins)-288 is sufficient for fish Keap1 molecules to fully function
study reports that the Keap1-Nrf2 (show NFE2L2 Proteins) system comprises discrete sensor sites, including the Keap1 cysteines Cys (show DNAJC5 Proteins)-151 and Cys (show DNAJC5 Proteins)-273, for a variety of Nrf2 (show NFE2L2 Proteins)-activating compounds
This gene encodes a protein containing KELCH-1 like domains, as well as a BTB/POZ domain. Kelch-like ECH-associated protein 1 interacts with NF-E2-related factor 2 in a redox-sensitive manner and the dissociation of the proteins in the cytoplasm is followed by transportation of NF-E2-related factor 2 to the nucleus. This interaction results in the expression of the catalytic subunit of gamma-glutamylcysteine synthetase. Two alternatively spliced transcript variants encoding the same isoform have been found for this gene.
kelch-like ECH-associated protein 1
, cytosolic inhibitor of Nrf2
, kelch-like family member 19
, kelch-like protein 19
, NRF2 cytosolic inhibitor
, ring canal protein