INT197569

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Context Info
Confidence 1.00
First Reported 2006
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 10
Total Number 11
Disease Relevance 3.11
Pain Relevance 0.10

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
nucleus 1
lung 1
NFE2L2 (Homo sapiens)
NFE2L2 - G364C (1)
Pain Link Frequency Relevance Heat
tolerance 3 86.64 High High
antidepressant 1 59.68 Quite High
anticonvulsant 1 57.00 Quite High
Paracetamol 7 43.68 Quite Low
Mechanosensation 1 43.00 Quite Low
Inflammation 11 34.64 Quite Low
Acute pain 1 33.52 Quite Low
Glutamate 3 19.12 Low Low
sSRI 3 5.00 Very Low Very Low Very Low
Pain 2 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Stress 59 99.28 Very High Very High Very High
Toxicity 108 95.08 Very High Very High Very High
Apoptosis 122 92.84 High High
Lung Cancer 68 90.28 High High
Cancer 163 89.80 High High
Death 128 89.32 High High
Adenocarcinoma 11 88.48 High High
Neuroblastoma 2 85.40 High High
Leukemia 14 85.08 High High
Heat Stress Disorders 1 75.92 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Under normal conditions, cells maintain low constitutive levels of Nrf2-target genes through constant ubiquitination and degradation of Nrf2, which is accomplished by the Keap1-dependent E3 ubiquitin ligase complex.
Protein_catabolism (degradation) of Nrf2
1) Confidence 1.00 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0 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.


Protein_catabolism (degradation) of Nrf2
2) Confidence 1.00 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.16 Pain Relevance 0
Similar to tBHQ, oridonin is able to block ubiquitination and degradation of Nrf2, resulting in the prolonged half-life of Nrf2.
Protein_catabolism (degradation) of Nrf2
3) Confidence 1.00 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.14 Pain Relevance 0
KEAP1 constitutively suppresses NRF2 activity</span> in the absence of stress; however, oxidants, xenobiotics, and electrophiles hamper the KEAP1-mediated proteasomal degradation of NRF2, which results in increased nuclear accumulation and, in turn, the transcriptional induction of target genes that ensure cell survival. [7,23] Recently, Padmanabhan et al. [24] reported a heterozygous somatic mutation (G430C) in KEAP1 in one lung cancer tumor and a G364C mutation in an adenocarcinoma and a small cell lung cancer cell line.
Protein_catabolism (degradation) of NRF2 (G364C) in lung associated with adenocarcinoma, stress, lung cancer and cancer
4) Confidence 0.95 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 0.74 Pain Relevance 0
Equal amounts of proteins were subjected to immunoblot analysis with Nrf2, Keap1, and ?
Protein_catabolism (analysis) of Nrf2
5) Confidence 0.89 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.24 Pain Relevance 0
Under normal conditions, cells maintain low constitutive levels of Nrf2-target genes through constant ubiquitination and degradation of Nrf2, which is accomplished by the Keap1-dependent E3 ubiquitin ligase complex.
Protein_catabolism (degradation) of Nrf2
6) Confidence 0.89 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0 Pain Relevance 0
Oridonin activated the Nrf2 signaling pathway at a low subtoxic dose and was able to stabilize Nrf2 by blocking Nrf2 ubiquitination and degradation, leading to accumulation of the Nrf2 protein and activation of the Nrf2-dependent cytoprotective response.
Protein_catabolism (degradation) of Nrf2
7) Confidence 0.66 Published 2008 Journal Environ Health Perspect Section Abstract Doc Link PMC2535615 Disease Relevance 0.26 Pain Relevance 0
Similar to tert-butylhydroquinone (tBHQ), it inhibits ubiquitination and degradation of Nrf2, resulting in stabilization of Nrf2 and activation of the Nrf2 signaling pathway.
Protein_catabolism (degradation) of Nrf2
8) Confidence 0.66 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.45 Pain Relevance 0
However, we have demonstrated that the ability of SQSTM1 to regulate the basal protein level of Nrf2 is also due to its capacity to alter the basal protein level of Keap1, by affecting its rate of degradation.
Protein_catabolism (degradation) of Nrf2
9) Confidence 0.35 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878012 Disease Relevance 0.09 Pain Relevance 0
Hence, Keap1 becomes saturated with Nrf2 that cannot be efficiently degraded, and thus newly synthesized Nrf2 is free to accumulate within the nucleus and transactivate antioxidant (or electrophile) response element-driven cytoprotective genes (8).
Protein_catabolism (degraded) of Nrf2 in nucleus
10) Confidence 0.35 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878012 Disease Relevance 0.08 Pain Relevance 0
Without such stresses, Nrf2 is normally repressed by the oxidative stress sensor Keap1 [38], which binds and degrades Nrf2 through the ubiquitin-proteasome system.
Protein_catabolism (degrades) of Nrf2 associated with stress
11) Confidence 0.05 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2822842 Disease Relevance 0.95 Pain Relevance 0.10

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