INT197562

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Context Info
Confidence 0.63
First Reported 2006
Last Reported 2010
Negated 0
Speculated 1
Reported most in Body
Documents 16
Total Number 17
Disease Relevance 6.78
Pain Relevance 0.08

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

endoplasmic reticulum (KEAP1) nucleolus (KEAP1) nucleus (KEAP1)
cytoplasm (KEAP1)
Anatomy Link Frequency
fat 1
A549 1
lung 1
NL20 1
KEAP1 (Homo sapiens)
Pain Link Frequency Relevance Heat
Pain 9 53.12 Quite High
Osteoarthritis 8 52.64 Quite High
Glutamate 15 5.00 Very Low Very Low Very Low
Inflammation 14 5.00 Very Low Very Low Very Low
palliative 6 5.00 Very Low Very Low Very Low
Paracetamol 5 5.00 Very Low Very Low Very Low
cytokine 1 5.00 Very Low Very Low Very Low
Immobilon 1 5.00 Very Low Very Low Very Low
imagery 1 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Lung Cancer 326 99.84 Very High Very High Very High
Repression 14 99.80 Very High Very High Very High
Cancer 640 99.56 Very High Very High Very High
Malignant Neoplastic Disease 24 99.48 Very High Very High Very High
Non-small-cell Lung Cancer 144 98.88 Very High Very High Very High
Stress 117 92.20 High High
Nash(non-alcoholic Steatohepatitis) 1 72.64 Quite High
Disease 20 71.68 Quite High
Targeted Disruption 21 69.60 Quite High
Neuroblastoma 8 66.76 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
B activity (22), and we have shown here that depletion of SQSTM1 is associated with an induction of Keap1 and repression of Nrf2.
Positive_regulation (induction) of Keap1 associated with repression
1) Confidence 0.63 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878012 Disease Relevance 0.17 Pain Relevance 0
SQSTM1 was dispensable for the induction of the Keap1-Nrf2 pathway, as Nrf2 activation by tert-butylhydroquinone or iodoacetamide was not affected by RNAi depletion of SQSTM1.
Positive_regulation (induction) of Keap1-Nrf2
2) Confidence 0.63 Published 2010 Journal The Journal of Biological Chemistry Section Abstract Doc Link PMC2878012 Disease Relevance 0 Pain Relevance 0
Furthermore, RNA interference (RNAi) depletion of SQSTM1 resulted in an increase in the protein level of Keap1 and a concomitant decrease in the protein level of Nrf2 in the absence of changes in Keap1 or Nrf2 mRNA levels.
Positive_regulation (increase) of Keap1
3) Confidence 0.63 Published 2010 Journal The Journal of Biological Chemistry Section Abstract Doc Link PMC2878012 Disease Relevance 0 Pain Relevance 0
Total NRF2 level was also higher in cancer cells, suggesting that there was increased stabilization of NRF2 in the absence of functional KEAP1.
Positive_regulation (absence) of KEAP1 associated with cancer
4) Confidence 0.50 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 0.92 Pain Relevance 0
, an extremely abundant nuclear oncoprotein, has been recently demonstrated to be an intranuclear dissociator of NRF2–KEAP1 complex and to upregulate expression of NRF2 target genes [36,37].
Positive_regulation (upregulate) of KEAP1
5) Confidence 0.50 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 0.77 Pain Relevance 0
Here we report a systematic analysis of the KEAP1 genomic locus in lung cancer patients and cell lines that revealed deletion, insertion, and missense mutations in functionally important domains of KEAP1 and a very high percentage of loss of heterozygosity at 19p13.2, suggesting that biallelic inactivation of KEAP1 in lung cancer is a common event.
Positive_regulation (inactivation) of KEAP1 in lung associated with lung cancer
6) Confidence 0.50 Published 2006 Journal PLoS Medicine Section Abstract Doc Link PMC1584412 Disease Relevance 0.80 Pain Relevance 0
We also sequenced KEAP1 in four non-malignant (normal) human lung epithelial cell lines (BEAS2B, NL20, HBE4, and NHBE) and found only the wild-type sequence (Table S3).


Positive_regulation (sequenced) of KEAP1 in NL20 associated with malignant neoplastic disease
7) Confidence 0.50 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 1.16 Pain Relevance 0
To determine the functional consequences of tumor-derived mutations on KEAP1 activity and resultant increases in NRF2 activity, we generated cDNAs harboring the same mutations seen in tumor cell lines, A549 (G333C) and H1435 (L413R).
Positive_regulation (increases) of KEAP1 in A549 associated with cancer
8) Confidence 0.46 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 0.98 Pain Relevance 0
The identification of KEAP1 mutations in a subset of NSCLC samples and the association between loss of functional KEAP1 and increased NRF2 activity extends the emerging paradigm whereby increased expression of antioxidants, detoxification enzymes, and drug transporters favors malignant progression and renders tumors resistant to chemotherapy.
Positive_regulation (increased) of KEAP1 associated with malignant neoplastic disease, cancer and non-small-cell lung cancer
9) Confidence 0.46 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 1.11 Pain Relevance 0
Under conditions of Nrf2 activation, the elevated expression of SQSTM1 may enable the targeting of Keap1 for degradation via autophagy, which in turn may (i) further contribute to the activation of Nrf2 and/or (ii) represent a means by which modified/inactivated Keap1 is removed/recycled to restore homeostasis in the pathway (Fig. 5).
Spec (may) Positive_regulation (enable) of Keap1
10) Confidence 0.46 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878012 Disease Relevance 0.38 Pain Relevance 0.08
In light of the observation of Komatsu and colleagues that ectopic expression of SQSTM1 causes a decrease in the ubiquitination of Nrf2, and in turn an increase in the total cellular level of the transcription factor (23), it is plausible that the decrease in total cellular level of Nrf2 following siRNA depletion of SQSTM1 reported here is due to an increase in Keap1-directed ubiquitination of Nrf2, facilitated by the higher basal level of Keap1.
Positive_regulation (increase) of Keap1-directed
11) Confidence 0.46 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878012 Disease Relevance 0.07 Pain Relevance 0
For example, the synthetic triterpenoid CDDO-Im has been shown to reduce hepatic lipid accumulation in mice on a high fat diet through activation of Keap1/Nrf2 signalling [49].
Positive_regulation (activation) of Keap1 in fat
12) Confidence 0.45 Published 2010 Journal Journal of Proteomics Section Body Doc Link PMC2891861 Disease Relevance 0.21 Pain Relevance 0
In si-SQSTM1-transfected cells, however, the half-life of Keap1 almost doubled to 21.1 h (Fig. 3D), indicating that siRNA depletion of SQSTM1 causes an increase in the basal protein level of Keap1 by slowing its rate of degradation.
Positive_regulation (increase) of Keap1
13) Confidence 0.42 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878012 Disease Relevance 0 Pain Relevance 0
The increased protein level of Keap1 in cells depleted of SQSTM1 by RNAi was linked to a decrease in its rate of degradation; the half-life of Keap1 was almost doubled by RNAi depletion of SQSTM1.
Positive_regulation (increased) of Keap1
14) Confidence 0.42 Published 2010 Journal The Journal of Biological Chemistry Section Abstract Doc Link PMC2878012 Disease Relevance 0 Pain Relevance 0
, so that induction of Keap1 results in a decrease in the activity of the NF-?
Positive_regulation (induction) of Keap1
15) Confidence 0.42 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878012 Disease Relevance 0.16 Pain Relevance 0
As with tBHQ, oridonin treatment was also effective in enhancing ubiquitination of Keap1 (Figure 3A, center panel).
Positive_regulation (enhancing) of Keap1
16) Confidence 0.33 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0 Pain Relevance 0
However, in this study, while spectrophotometric assays of absorbance shifts were used to support the conclusion that Keap1 is modified by sulforaphane, no direct evidence was presented for covalent labeling of Keap1.
Positive_regulation (modified) of Keap1
17) Confidence 0.16 Published 2007 Journal BMC Cancer Section Body Doc Link PMC2071920 Disease Relevance 0.06 Pain Relevance 0

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