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 maintains 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 N-terminal BTB/POZ domain and a C-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 IKKBeta degradation (11).
Applications:Suitable for use in Western Blot, Immunohistochemistry and ELISA.
Other applications not tested.
Recommended Dilution:Western Blot: 1:500-1:2000, incubate membrane with diluted primary antibody in TBS, 5% milk, 0.1% Tween 20 at 4°C with gentle shaking, overnight
Immunohistochemistry: 1:50-1:200ELISA (peptide): 1:20,000-1:40,000Optimal dilutions to be determined by the researcher.
Storage and Stability:May be stored at 4°C for short-term only.
Aliquot to avoid repeated freezing and thawing.
Store at -20°C.
Aliquots are stable for 12 months after receipt.
For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap.
仕様
Size:100ul
Host:rabbit
Source Antibody:human
Grade:Affinity Purified
Purity:Purified by immunoaffinity chromatography from serum.
Form:Supplied as a liquid in PBS, pH 7.4, 0.02% sodium azide, 50% glycerol.
Specificity:Recognizes endogenous levels of total human KEAP1. Species Crossreactivity: mouse and rat
Isotype:IgG
Calc Applications Abbrev:E IHC WB
Calc Crossreactivity:Hu Mo Rt
Immunogen:Synthetic peptide corresponding to human KEAP1.