INT125525

Context Info Confidence 0.45 First Reported 2005 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 7 Total Number 11 Disease Relevance 2.72 Pain Relevance 1.21

nucleoplasm (PRKDC) protein modification process (PRKDC) nucleus (PRKDC) enzyme binding (PRKDC) DNA binding (PRKDC) transcription factor binding (PRKDC)

Anatomy Link Frequency neurons 2 brain 2 neuronal 1 synapses 1 PRKDC (Homo sapiens)

Pain Link Frequency Relevance Heat amygdala 290 97.32 Pyramidal cell 40 94.24 nMDA receptor 125 91.04 Kinase C 4 90.04 agonist 19 87.04 Pain 18 79.84 withdrawal 45 72.80 Inflammation 19 72.12 adenocard 29 69.68 cINOD 3 66.80

Disease Link Frequency Relevance Heat Syndrome 107 99.24 Infection 8 98.12 Apoptosis 15 95.40 Increased Venous Pressure Under Development 12 90.40 Hyperplasia 1 88.00 Prostate Cancer 4 78.96 Autism 1570 78.92 INFLAMMATION 25 72.12 Cognitive Disorder 215 68.08 Targeted Disruption 39 63.36

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Western blot analysis with primary cortical neurons expressing mutant Htt showed that protein levels of Ku70 and Ku80 but not of DNA–PKcs transiently increased at day 1, decreased from day 1 to day 6 after infection, and returned to the initial level (Fig. 6, A–C).

Positive_regulation (increased) of DNA-PKcs in neurons associated with infection

1) Confidence 0.45 Published 2010 Journal The Journal of Cell Biology Section Body Doc Link PMC2867301 Disease Relevance 0.10 Pain Relevance 0

One key nuclear function of EGFR is phosphorylation and activation of DNA-dependent protein kinase (DNA-PK), an enzyme that is involved in repair of breaks in double-stranded DNA caused by radiation and chemotherapy.18,19 EGFR localizing to the nuclear compartment can also enter transcriptional complexes and bind to the promoter region of cyclin D1 to promote cell cycle progression and increase cellular proliferation.20 EGFR inhibition delays the repair of chemotherapy-induced DNA damage via modulation of DNA repair genes such as XRCC1 and ERCC1, which could explain some of the increased activity of cisplatin when combined with EGFR inhibitors such as cetuximab.21–23

Positive_regulation (activation) of DNA-dependent protein kinase associated with hyperplasia

2) Confidence 0.10 Published 2010 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2921255 Disease Relevance 0.24 Pain Relevance 0

Expression of constitutively active PKCs induced an increase in NF-kappa B transcriptional activity and NAG-1 protein levels in LNCaP cells.

Positive_regulation (Expression) of PKCs

3) Confidence 0.08 Published 2005 Journal J. Biol. Chem. Section Abstract Doc Link 15757899 Disease Relevance 0.44 Pain Relevance 0.26

Thus, downstream effects of conventional, Ca2+-activated PKCs include a direct phosphorylation of p47phox, which leads to membrane translocation of cytosolic components (Fig. 1).

Positive_regulation (activated) of PKCs

4) Confidence 0.03 Published 2008 Journal J Leukoc Biol Section Body Doc Link PMC2567897 Disease Relevance 0.06 Pain Relevance 0.07

At least 12 different PKC isoforms have been characterized so far, and these can be grouped into the following three subgroups: conventional PKCs (?

Positive_regulation (grouped) of PKCs

5) Confidence 0.03 Published 2008 Journal J Leukoc Biol Section Body Doc Link PMC2567897 Disease Relevance 0 Pain Relevance 0

This catalyzes the conversion of GTP to cGMP, which increases the activity of a series of cGMP-dependent protein kinases (PKCs), particularly the I?

Positive_regulation (increases) of PKCs

6) Confidence 0.03 Published 2010 Journal International Journal of Vascular Medicine Section Body Doc Link PMC3003984 Disease Relevance 0.16 Pain Relevance 0.07

The amygdala contains relatively higher numbers of inhibitory interneurons than in the neocortex and reducing inhibition may be more effective in causing hyper-functionality than hyper-connecting through glutamatergic synapses.

Positive_regulation (causing) of hyper-functionality in synapses associated with amygdala

7) Confidence 0.01 Published 2010 Journal Frontiers in Human Neuroscience Section Body Doc Link PMC3010743 Disease Relevance 0.37 Pain Relevance 0.36

In the brain, this common molecular syndrome is proposed to have a dual effect of causing hyper-reactivity and hyper-plasticity of microcircuits to produce hyper-functionality (Figure 5).

Positive_regulation (causing) of hyper-plasticity in brain associated with syndrome

8) Confidence 0.01 Published 2010 Journal Frontiers in Human Neuroscience Section Body Doc Link PMC3010743 Disease Relevance 0.56 Pain Relevance 0.03

In summary, the neuronal network response in VPA-treated offspring is greatly amplified, resulting in hyper-reactivity to network stimulation as a common denominator between several distinct brain regions (Figure 1).

Positive_regulation (resulting) of hyper-reactivity in neuronal

9) Confidence 0.01 Published 2010 Journal Frontiers in Human Neuroscience Section Body Doc Link PMC3010743 Disease Relevance 0.15 Pain Relevance 0.21

In the brain, this common molecular syndrome is proposed to have a dual effect of causing hyper-reactivity and hyper-plasticity of microcircuits to produce hyper-functionality (Figure 5).

Positive_regulation (causing) of hyper-reactivity in brain associated with syndrome

10) Confidence 0.01 Published 2010 Journal Frontiers in Human Neuroscience Section Body Doc Link PMC3010743 Disease Relevance 0.51 Pain Relevance 0.03

Several potential mechanisms can be excluded to underlie this hyper-reactivity, such as more excitable neurons or stronger excitatory synaptic connections, or changes in morphology.

Positive_regulation (underlie) of hyper-reactivity in neurons

11) Confidence 0.01 Published 2010 Journal Frontiers in Human Neuroscience Section Body Doc Link PMC3010743 Disease Relevance 0.14 Pain Relevance 0.19

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