Search results for KEAP1

Showing 19 results out of 92

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Types

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Protein (3 results from a total of 3)

Identifier: R-HSA-976038
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: KEAP1: Q14145
Identifier: R-HSA-9766647
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: KEAP1: Q14145
Identifier: R-HSA-6782766
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: KEAP1: Q14145

DNA Sequence (1 results from a total of 1)

Identifier: R-HSA-8962726
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: ENSEMBL: ENSEMBL:ENSG00000079999

Reaction (5 results from a total of 70)

Identifier: R-HSA-9766645
Species: Homo sapiens
Compartment: cytosol
KEAP1 is ubiquitinated by the CUL3:RBX1 complex in an SQSTM1-dependent manner (Zhang et al, 2005). Ubiquitination of KEAP1 renders it a substrate for SQSTM1-dependent degradation through the selective autophagy pathway (Zhang et al, 2005; Taguchi et al, 2012).
Identifier: R-HSA-9766677
Species: Homo sapiens
Compartment: cytosol
SQSTM1 targets ubiquitinated cargo such as KEAP1 for degradation through the selective autophagy pathway. In addition to binding to the KEAP1, SQSTM1 also interacts with LC3 proteins that coat the forming autophagosome (Bjorkoy et al, 2005; Lee et al, 2017; Jain et al, 2010; reviewed in Jiang et al, 2015). Interaction between SQSTM1, ubiquitinated KEAP1 and LC3 proteins is enhanced through the binding of SESN1 and SESN2 proteins (Bae et al, 2013; Ro et al, 2014).
Identifier: R-HSA-9796040
Species: Homo sapiens
Compartment: nucleoplasm
NFE2L2 (NRF2) controls its own degradation by regulating the expression and induction of the INrf2 (KEAP1) gene. The antioxidant treatment of cells led to nuclear localization and stabilization of Nrf2 and induction of INrf2 gene expression (PMID: 17925401)
Identifier: R-HSA-9766687
Species: Homo sapiens
Compartment: cytosol
SESN1 and SESN2 are proteins with roles in oxidative stress response. Both SESN1 and SESN2 interact with SQSTM1 in the context of a KEAP1:CUL3:RBX1 complex to promote the degradation of KEAP1 by selective autophagy (Bae et al, 2013; Ro et al, 2014). SESN1 and SESN2 may increase the binding affinity of SQSTM1 for its KEAP1 substrate (Bae et al, 2013).
Identifier: R-HSA-9796050
Species: Homo sapiens
Compartment: nucleoplasm
NFE2L2 (NRF2) controls its own degradation by regulating the expression and induction of the INrf2 (KEAP1) gene. The antioxidant treatment of cells led to nuclear localization and stabilization of Nrf2 and induction of INrf2 gene expression (PMID: 17925401)

Pathway (3 results from a total of 3)

Identifier: R-HSA-9755511
Species: Homo sapiens
The KEAP1:NFE2L2 (KEAP1-NRF2, Kelch-like ECH-associated protein 1-Nuclear Factor (erythroid-derived 2)-like 2) regulatory pathway plays a central role in protecting cells against multiple homeostatic responses including adaptation to oxidative, inflammatory, metabolic, proteotoxic and xenobiotic stresses. The NFE2L2 transcriptome has been implicated in protection against many chronic diseases including cardiovascular, metabolic, neurodgenerative and respiratory diseases (reviewed in Cuadrado et al, 2018; Baird and Yamamoto, 2020). In cancer, NFE2L2 plays a critical role in the metabolic reprogramming, directing metabolic intermediates into the Warburg and pentose phosphate pathways to support proliferative growth and redox homeostasis (reviewed in He et al, 2020; Ge et al, 2020; Hayes et al, 2020; Kitamura and Hotomashi, 2018)

KEAP1 is a redox sensor that together with CUL3/RBX1 forms part of an E3 ubiquitin ligase, which tightly regulates the activity of the transcription factor NFE2L2 by targeting it for ubiquitination and proteasome-dependent degradation. Oxidative modifications or electrophile adduct formation with redox-sensitive cysteines within KEAP1 renders this protein unable to target bound NFE2L2 for ubiquitination and allows newly translated NFE2L2 to accumulate within the cell and translocate to the nucleus where it can promote its transcriptional program (reviewed in Cuadrado et al, 2019; Baird and Yamamoto, 2020).
Identifier: R-HSA-9759194
Species: Homo sapiens
Compartment: nucleoplasm
In response to chemical and other stressors, the constitutive degradation of NFE2L2 by the KEAP1:CUL3:26S proteasome system is disrupted, allowing NFE2L2 to accumulate. Stabilized NFE2L2 translocates to the nucleus where it binds to antioxidant response elements (AREs) in the promoters and enhancers of target genes to upregulate their expression (reviewed in Baird and Yamamoto, 2020).
Identifier: R-HSA-9762114
Species: Homo sapiens
In addition to KEAP1:CUL3-mediated degradation in the cytosol, NFE2L2 appears to also be subject to degradation by a BTRC:CUL1 E3 ligase (reviewed in Cuadrado, 2015; Baird and Yamamoto, 2020; Yamamoto et al, 2018). Degradation by the BTRC:CUL1 pathway is mediated by interaction with the NFE2L2 Neh6 domain, and is stimulated by GSK3B-mediated phosphorylation of the Neh6 DSGIS motif. GSK3B-dependent Neh6 phosphorylation is primed by the phosphorylation of a cluster of adjacent serines by unknown kinase(s) (Salazar et al, 2006; Rada et al, 2011; Rada et L, 2012; Rojo et al, 2012; Chen et al, 2017; reviewed in Baird and Yamamoto, 2020). Inhibitory phosphorylation of GSK3B by activated PI3K/AKT signaling relieves BTRC:CUL1-mediated NFE2L2 degradation and provides a biochemical link between activated PI3K signaling and increased NFE2L2 pathway activity (reviewed in Cuadrado, 2015; Baird and Yamamoto, 2020; Yamamoto et al, 2018).

Complex (5 results from a total of 13)

Identifier: R-HSA-8932333
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-9758078
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-9795984
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-9766644
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-8932286
Species: Homo sapiens
Compartment: cytosol

Set (2 results from a total of 2)

Identifier: R-HSA-6781778
Species: Homo sapiens
Compartment: cytosol, plasma membrane
Identifier: R-HSA-6782776
Species: Homo sapiens
Compartment: cytosol, plasma membrane
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