Render Target: STATIC
Render Timestamp: 2024-12-12T10:44:42.959Z
Commit: 611277b6de3cd1bb065350b6ef8d63df412b7185
XML generation date: 2024-09-27 18:08:07.728
Product last modified at: 2024-12-05T12:45:34.209Z
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PDP - Template Name: Polyclonal Antibody
PDP - Template ID: *******59c6464

KEAP1 (P586) Antibody #4678

Filter:
  • WB
  • IP

    Supporting Data

    REACTIVITY H M R
    SENSITIVITY Endogenous
    MW (kDa) 60-64
    SOURCE Rabbit
    Application Key:
    • WB-Western Blotting 
    • IP-Immunoprecipitation 
    Species Cross-Reactivity Key:
    • H-Human 
    • M-Mouse 
    • R-Rat 

    Product Information

    Product Usage Information

    Application Dilution
    Western Blotting 1:1000
    Immunoprecipitation 1:50

    Storage

    Supplied in 10 mM sodium HEPES (pH 7.5), 150 mM NaCl, 100 µg/ml BSA and 50% glycerol. Store at –20°C. Do not aliquot the antibody.

    Protocol

    Specificity / Sensitivity

    KEAP1 (P586) Antibody detects endogenous levels of total KEAP1 protein.

    Species Reactivity:

    Human, Mouse, Rat

    Source / Purification

    Polyclonal antibodies are produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Pro586 of human KEAP1 protein. Antibodies were purified by protein A and peptide affinity chromatography.

    Background

    The nuclear factor-like 2 (NRF2) transcriptional activator binds antioxidant response elements (ARE) of target gene promoter regions to regulate expression of oxidative stress response genes. Under basal conditions, the NRF2 inhibitor INrf2 (also called KEAP1) binds and retains NRF2 in the cytoplasm where it can be targeted for ubiquitin-mediated degradation (1). Small amounts of constitutive nuclear NRF2 maintain cellular homeostasis through regulation of basal expression of antioxidant response genes. Following oxidative or electrophilic stress, KEAP1 releases NRF2, thereby allowing the activator to translocate to the nucleus and bind to ARE-containing genes (2). The coordinated action of NRF2 and other transcription factors mediates the response to oxidative stress (3). Altered expression of NRF2 is associated with chronic obstructive pulmonary disease (COPD) (4). NRF2 activity in lung cancer cell lines directly correlates with cell proliferation rates, and inhibition of NRF2 expression by siRNA enhances anti-cancer drug-induced apoptosis (5).
    The NRF2 repressor KEAP1 contains an amino terminal BTB/POZ domain and a carboxyl terminal KELCH domain (6,7). The KELCH domain is required for interacting with NRF2 and the BTB/POZ domain functions in binding Cul3 E3 ubiquitin ligase (8-10). Under normal conditions, the complex leads to the cytoplasmic sequestration and ubiquitin-mediated proteasomal degradation of NRF2. Electrophilic modification of KEAP1 leads to disassociation of the NRF2/KEAP1 complex. KEAP1 also targets the down regulation of NF-κB activity by targeting IKKβ degradation (11). Mutation of the corresponding KEAP1 gene is seen in lung cancer cases and can lead to uncontrolled activation of NRF2 (12-14).
    For Research Use Only. Not For Use In Diagnostic Procedures.
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