INT101832

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Context Info
Confidence 0.67
First Reported 2002
Last Reported 2010
Negated 1
Speculated 0
Reported most in Body
Documents 16
Total Number 16
Disease Relevance 7.41
Pain Relevance 0.12

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

cytosol (NFE2L2) plasma membrane (NFE2L2) nucleus (NFE2L2)
DNA binding (NFE2L2) cytoplasm (NFE2L2)
Anatomy Link Frequency
epithelial cells 4
nucleus 2
NFE2L2 (Homo sapiens)
Pain Link Frequency Relevance Heat
cINOD 11 69.28 Quite High
Inflammation 29 27.52 Quite Low
aspirin 10 5.00 Very Low Very Low Very Low
Glutamate 10 5.00 Very Low Very Low Very Low
palliative 7 5.00 Very Low Very Low Very Low
Paracetamol 5 5.00 Very Low Very Low Very Low
COX2 2 5.00 Very Low Very Low Very Low
adenocard 2 5.00 Very Low Very Low Very Low
metalloproteinase 2 5.00 Very Low Very Low Very Low
Pain 1 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Toxicity 76 100.00 Very High Very High Very High
Repression 8 100.00 Very High Very High Very High
Cancer 786 99.60 Very High Very High Very High
Lung Cancer 388 92.96 High High
Stress 75 87.52 High High
Death 104 85.52 High High
Targeted Disruption 8 85.32 High High
Adenocarcinoma 53 82.68 Quite High
Breast Cancer 24 78.08 Quite High
Non-small-cell Lung Cancer 168 76.92 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Consistent with this idea, over-expression of Nrf2 increased GCLC reporter gene expression and over-expression of KIAA0132 inhibited GCLC reporter gene activity as well as inhibited indomethacin-induced increases in the expression of GCLC.
Positive_regulation (over-expression) of Gene_expression (over-expression) of Nrf2
1) Confidence 0.67 Published 2002 Journal Free Radic. Biol. Med. Section Abstract Doc Link 11909699 Disease Relevance 0 Pain Relevance 0.12
Transfection of NRF2 siRNA in cancer cells decreased the NRF2 message by 80% and simultaneously downregulated the expression of NRF2 target genes (Figure 6B).
Positive_regulation (Transfection) of Gene_expression (Transfection) of NRF2 associated with cancer
2) Confidence 0.66 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 0.53 Pain Relevance 0
Conversely, inhibition of KEAP1 expression by siRNA induced the expression of NRF2-driven genes in BEAS2B cells (Figure 6C).


Positive_regulation (induced) of Gene_expression (expression) of NRF2
3) Confidence 0.66 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 0.47 Pain Relevance 0
Taken together, these results indicate that oridonin activates the Nrf2 pathway by inhibiting ubiquitination and degradation of Nrf2, leading to an increase in Nrf2 protein level and activation of the Nrf2-dependent response.


Positive_regulation (activation) of Gene_expression (level) of Nrf2 protein
4) Confidence 0.50 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.17 Pain Relevance 0
Taken together, these results indicate that oridonin activates the Nrf2 pathway by inhibiting ubiquitination and degradation of Nrf2, leading to an increase in Nrf2 protein level and activation of the Nrf2-dependent response.


Positive_regulation (activation) of Gene_expression (level) of Nrf2
5) Confidence 0.50 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.17 Pain Relevance 0
This decrease in Nrf2 protein level in response to high doses of oridonin is not due solely to cell toxicity because Keap1 or ?
Neg (not) Positive_regulation (because) of Gene_expression (level) of Nrf2 protein associated with toxicity
6) Confidence 0.50 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.75 Pain Relevance 0
Taken together, these results indicate that oridonin activates the Nrf2 pathway by inhibiting ubiquitination and degradation of Nrf2, leading to an increase in Nrf2 protein level and activation of the Nrf2-dependent response.


Positive_regulation (increase) of Gene_expression (level) of Nrf2
7) Confidence 0.50 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.17 Pain Relevance 0
Taken together, these results indicate that oridonin activates the Nrf2 pathway by inhibiting ubiquitination and degradation of Nrf2, leading to an increase in Nrf2 protein level and activation of the Nrf2-dependent response.


Positive_regulation (increase) of Gene_expression (level) of Nrf2 protein
8) Confidence 0.50 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.16 Pain Relevance 0
All four PT tissues harboring KEAP1 mutations showed increased NRF2 staining in the nucleus and cytoplasm (Figure 3A, part a).
Positive_regulation (increased) of Gene_expression (staining) of NRF2 in nucleus
9) Confidence 0.48 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 1.23 Pain Relevance 0
Increased NRF2 staining and NRF2-dependent enzyme activities in tumor samples with wild-type KEAP1 suggests that there are other possible mechanisms operating in tumor cells that contribute to increased stabilization and activation of NRF2 [11,36].
Positive_regulation (Increased) of Gene_expression (staining) of NRF2 associated with cancer
10) Confidence 0.48 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 0.72 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 Gene_expression (expression) of NRF2
11) Confidence 0.48 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 0.77 Pain Relevance 0
Increased NRF2 staining and NRF2-dependent enzyme activities in tumor samples with wild-type KEAP1 suggests that there are other possible mechanisms operating in tumor cells that contribute to increased stabilization and activation of NRF2 [11,36].
Positive_regulation (Increased) of Gene_expression (staining) of NRF2 associated with cancer
12) Confidence 0.48 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 0.72 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 Gene_expression (expression) of NRF2
13) Confidence 0.48 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 0.77 Pain Relevance 0
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 Gene_expression (repression) of Nrf2 associated with repression
14) Confidence 0.27 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878012 Disease Relevance 0.17 Pain Relevance 0
Curcumin exposure resulted in an increase in nuclear Nrf2 content in bronchial epithelial cells [60] and in increased expression of Nrf2 in renal epithelial cells [61].
Positive_regulation (increased) of Gene_expression (expression) of Nrf2 in epithelial cells
15) Confidence 0.21 Published 2004 Journal J Carcinog Section Body Doc Link PMC421747 Disease Relevance 0.30 Pain Relevance 0
Curcumin exposure resulted in an increase in nuclear Nrf2 content in bronchial epithelial cells [60] and in increased expression of Nrf2 in renal epithelial cells [61].
Positive_regulation (resulted) of Gene_expression (expression) of Nrf2 in epithelial cells
16) Confidence 0.21 Published 2004 Journal J Carcinog Section Body Doc Link PMC421747 Disease Relevance 0.32 Pain Relevance 0

General Comments

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