INT110925

Context Info Confidence 0.49 First Reported 2002 Last Reported 2010 Negated 2 Speculated 1 Reported most in Body Documents 14 Total Number 17 Disease Relevance 6.22 Pain Relevance 1.98

cytosol (JUN) nucleoplasm (JUN) nuclear chromosome (JUN) aging (JUN) nucleus (JUN) DNA binding (JUN)

Anatomy Link Frequency macrophages 2 lymph node 2 chondrocytes 2 primary sensory neuron 2 JUN (Homo sapiens)

Pain Link Frequency Relevance Heat Kappa opioid receptor 3 100.00 lidocaine 6 99.62 opioid receptor 10 99.20 Analgesic 1 96.92 Neuritis 1 96.56 dorsal root ganglion 2 88.80 Nicotine 96 87.20 Paracetamol 3 86.48 local anesthetic 2 81.44 COX2 1 81.24

Disease Link Frequency Relevance Heat Metastasis 13 100.00 Hypoxia 5 99.90 Infection 82 99.58 Drug Induced Neurotoxicity 7 99.36 Apoptosis 425 98.98 Melanoma 73 98.80 Cancer 98 98.56 Dengue 3 96.72 Neuritis 1 96.56 Adhesions 3 95.84

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

METHODS: The authors used primary sensory neuron cultures and pheochromocytoma cell line cultures to detect time-dependent activation of the p38 MAPK or related pathways such as extracellular signal-regulated kinases and c-jun N-terminal kinases.

Positive_regulation (time-dependent) of Positive_regulation (activation) of c-jun in primary sensory neuron

1) Confidence 0.49 Published 2006 Journal Anesthesiology Section Body Doc Link 17065898 Disease Relevance 0 Pain Relevance 0

Phosphatidylinositol-3 kinase is distinctively required for mu-, but not kappa-opioid receptor-induced activation of c-Jun N-terminal kinase.

Positive_regulation (required) of Positive_regulation (activation) of c-Jun associated with kappa opioid receptor

2) Confidence 0.49 Published 2004 Journal J. Neurochem. Section Title Doc Link 15056283 Disease Relevance 0.08 Pain Relevance 0.47

Additional work by Hideshima et al revealed that bortezomib activation seemed to be dependent on the activation of c-Jun NH2-terminal kinase (JNK) and subsequently caspases-8 and caspase-3 that elicit DNA damage and apoptosis.

Positive_regulation (activation) of Positive_regulation (activation) of c-Jun associated with apoptosis

3) Confidence 0.49 Published 2010 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2990320 Disease Relevance 0.49 Pain Relevance 0.04

Neurotoxicity of lidocaine involves specific activation of the p38 mitogen-activated protein kinase, but not extracellular signal-regulated or c-jun N-terminal kinases, and is mediated by arachidonic acid metabolites.

Positive_regulation (mediated) of Positive_regulation (activation) of c-jun associated with drug induced neurotoxicity and lidocaine

4) Confidence 0.49 Published 2006 Journal Anesthesiology Section Title Doc Link 17065898 Disease Relevance 0.37 Pain Relevance 0.41

However, pBrBzGSCp(2) did not lead to tau "hyper"-phosphorylation despite activation of p38 mitogen-activated protein kinase and c-Jun NH(2)-terminal kinase but rather activated protein phosphatases 2 and induced tau dephosphorylation at the Ser(202)/Thr(205) and Ser(396)/Ser(404) epitopes.

Neg (not) Positive_regulation (lead) of Positive_regulation (activation) of c-Jun

5) Confidence 0.45 Published 2006 Journal J. Neurosci. Res. Section Abstract Doc Link 16555297 Disease Relevance 0.62 Pain Relevance 0.10

RESULTS: SC236 treatment induced apoptosis in gastric cancer cells and caused activation of p38 and stress-activated protein kinase/jun kinase, but down-regulated Akt/PKB.

Positive_regulation (caused) of Positive_regulation (activation) of jun

6) Confidence 0.45 Published 2006 Journal Digestion Section Body Doc Link 16641552 Disease Relevance 0.16 Pain Relevance 0

After binding of its ligand the tumor GnRH receptor couples to G-protein alphai and activates a variety of intracellular signaling mechanisms. (1) Through activation of a protein tyrosine phosphatase, autophosphorylation of growth factor receptors is reverted leading to an inhibition of mitogenic signaling and reduced cell proliferation. (2) Through activation of nuclear factor kappa B antiapoptotic mechanisms are induced protecting tumor cells from apoptosis induced, for example, by doxorubicin. (3) Through activation of the Jun kinase pathway AP-1 is induced, leading to cell cycle arrest in the G0/G1 phase.

Positive_regulation (induced) of Positive_regulation (activation) of Jun associated with cancer and apoptosis

7) Confidence 0.39 Published 2003 Journal Endocr. Relat. Cancer Section Abstract Doc Link 12790790 Disease Relevance 0.81 Pain Relevance 0.19

Hypoxia can promote lymph node metastasis via up-regulation of PLAUR [39], and up-regulation of HIF1a, JUN and PLAUR in our invasive cell lines hints at possible activation of JUN/AP1 and HIF/ARNT pathways in melanoma (Figure 5).

Positive_regulation (promote) of Spec (possible) Positive_regulation (activation) of JUN in lymph node associated with melanoma, hypoxia and metastasis

8) Confidence 0.29 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2794539 Disease Relevance 1.75 Pain Relevance 0

The NFAT inhibitory activity of AM404 seems to be quite specific since this compound did not interfere with the signaling pathways leading to AP-1 or NF-kappaB activation.

Positive_regulation (leading) of Positive_regulation (activation) of AP-1

9) Confidence 0.27 Published 2007 Journal Biochem. Pharmacol. Section Abstract Doc Link 17196940 Disease Relevance 0 Pain Relevance 0.24

B signaling pathways leading to the regulation of gene expression in chondrocytes include the activation of the transcription factors AP-1 and NF-?

Positive_regulation (activation) of Positive_regulation (factors) of AP-1 in chondrocytes

10) Confidence 0.27 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC1906809 Disease Relevance 0 Pain Relevance 0

Interestingly, MDM2 was induced in the U versus WT comparison in addition to the significant induction of JUN.

Positive_regulation (induced) of Positive_regulation (induction) of JUN

11) Confidence 0.16 Published 2010 Journal BMC Genomics Section Body Doc Link PMC2996966 Disease Relevance 0.44 Pain Relevance 0

However, we cannot rule out the possibility that a bacterial T3SS effector protein expressed intracellularly also contributes to the induction of JUN.

Positive_regulation (contributes) of Positive_regulation (induction) of JUN

12) Confidence 0.14 Published 2010 Journal BMC Genomics Section Body Doc Link PMC2996966 Disease Relevance 0.43 Pain Relevance 0.07

Despite the induction of p53-responsive genes, p53 itself was not induced in WTSTS or in WT cells most likely due to significant JUN induction since JUN represses p53.

Neg (not) Positive_regulation (induced) of Positive_regulation (induction) of JUN

13) Confidence 0.14 Published 2010 Journal BMC Genomics Section Body Doc Link PMC2996966 Disease Relevance 0.28 Pain Relevance 0

The proliferative effects of oxytocin appear to be Gq-linked and likely involve MAPK activation, leading to c-fos and c-jun induction.

Positive_regulation (leading) of Positive_regulation (induction) of c-jun

14) Confidence 0.08 Published 2010 Journal CNS Neuroscience & Therapeutics Section Body Doc Link PMC2972642 Disease Relevance 0 Pain Relevance 0.04

A recent study with human lung macrophages revealed an increase in MAPK phosphorylation and activation of the MAPK/AP-1 pathway caused by cigarette smoke [37].

Positive_regulation (increase) of Positive_regulation (activation) of AP-1 in macrophages

15) Confidence 0.07 Published 2010 Journal Respir Res Section Body Doc Link PMC2845563 Disease Relevance 0.17 Pain Relevance 0.32

But induction of the COX-2 promoter via AP-1 is very unlikely since there are no binding sites for AP-1 within the used COX-2 promoter fragment.

Positive_regulation (unlikely) of Positive_regulation (induction) of AP-1

16) Confidence 0.03 Published 2002 Journal BMC Mol Biol Section Body Doc Link PMC140029 Disease Relevance 0 Pain Relevance 0

IL-8 induction by DEN2V infection was associated with activation of NF- kappa B and activator protein-1 (AP-1) in HEK293A cells but only with activation of AP-1 in HepG2 cells.

Positive_regulation (activation) of Positive_regulation (activation) of AP-1 associated with infection

17) Confidence 0.02 Published 2006 Journal J. Infect. Dis. Section Abstract Doc Link 16544247 Disease Relevance 0.62 Pain Relevance 0.10

General Comments

This test has worked.