INT103282

Context Info Confidence 0.66 First Reported 2002 Last Reported 2009 Negated 0 Speculated 0 Reported most in Abstract Documents 12 Total Number 14 Disease Relevance 7.28 Pain Relevance 2.65

nucleoplasm (ATF4) DNA binding (ATF4) microtubule organizing center (ATF4) cytoplasm (ATF4) nucleus (ATF4) cytoskeleton (ATF4)

Anatomy Link Frequency reticulum 1 ATF4 (Homo sapiens)

Pain Link Frequency Relevance Heat tetrodotoxin 8 98.36 cINOD 28 94.24 Glutamate 1 90.24 Action potential 2 87.20 nMDA receptor 4 85.28 agonist 2 78.60 endometriosis 2 77.04 pain pelvic 2 75.72 Inflammation 21 75.00 Inflammatory response 4 65.12

Disease Link Frequency Relevance Heat Cancer 157 99.56 Stress 234 97.44 Apoptosis 100 96.24 Stomach Cancer 10 94.36 Starvation 2 93.80 Colon Cancer 40 91.88 Hypoxia 55 90.16 INFLAMMATION 35 79.96 Endometriosis 3 77.04 Drug Induced Neurotoxicity 6 75.96

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Event

Anatomy

Negation

Speculation

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Disease term

Experiments using siRNA and an intracellular Ca(2+) chelator revealed that Ca(2+)-dependent up-regulation of ATF4 and CHOP is involved in this up-regulation of PUMA.

Positive_regulation (up-regulation) of ATF4

1) Confidence 0.66 Published 2007 Journal Biochem. Biophys. Res. Commun. Section Abstract Doc Link 17368424 Disease Relevance 0.84 Pain Relevance 0.21

Both the ATF4 and ATF6 pathways were activated by celecoxib, and suppression of ATF4 and ATF6 mRNA expression by small interfering RNA (siRNA) inhibited the celecoxib-dependent up-regulation of ORP150.

Positive_regulation (activated) of ATF4

2) Confidence 0.64 Published 2007 Journal Mol. Pharmacol. Section Abstract Doc Link 17167033 Disease Relevance 0.70 Pain Relevance 0.08

The celecoxib-mediated up-regulation of S100P was suppressed by the transfection of cells with small interfering RNA for activating transcription factor 4 (ATF4), a transcription factor involved in the endoplasmic reticulum stress response.

Positive_regulation (activating) of ATF4 in reticulum associated with stress

3) Confidence 0.59 Published 2009 Journal J. Biol. Chem. Section Abstract Doc Link 19073601 Disease Relevance 0.79 Pain Relevance 0.32

Celecoxib increased the intracellular Ca2+ concentration, while 1,2-bis(2-aminophenoxy)ethane-N,N,N'N'-tetraacetic acid, an intracellular Ca2+ chelator, inhibited the upregulation of GRP78 and ATF4.

Positive_regulation (upregulation) of ATF4

4) Confidence 0.52 Published 2006 Journal Oncogene Section Abstract Doc Link 16205636 Disease Relevance 0.74 Pain Relevance 0.35

Celecoxib administration led to an increase in the intracellular concentration of Ca2+, whereas 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester, an intracellular Ca2+ chelator, inhibited the up-regulation of ORP150 and the activation of the ATF4 and ATF6 pathways.

Positive_regulation (activation) of ATF4

5) Confidence 0.43 Published 2007 Journal Mol. Pharmacol. Section Abstract Doc Link 17167033 Disease Relevance 0.85 Pain Relevance 0.06

-phosphorylation the translation of most mRNAs is inhibited, but paradoxically the translation of activating transcription factor 4 (ATF4) is increased.

Positive_regulation (activating) of ATF4

6) Confidence 0.40 Published 2007 Journal BMC Pharmacol Section Body Doc Link PMC2194763 Disease Relevance 0.92 Pain Relevance 0

These results suggest that the Ca2+-dependent activation of the PERK-eIF2alpha-ATF4 pathway is involved in the upregulation of ER chaperones by celecoxib.

Positive_regulation (activation) of ATF4

7) Confidence 0.38 Published 2006 Journal Oncogene Section Abstract Doc Link 16205636 Disease Relevance 0.58 Pain Relevance 0.24

phosphorylation promotes the induction of activating transcription factor 4 (ATF4) through a mechanism that relies upon unique features in its 5' untranslated region [54].

Positive_regulation (activating) of ATF4

8) Confidence 0.31 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2527015 Disease Relevance 0.42 Pain Relevance 0.03

phosphorylation promotes the induction of activating transcription factor 4 (ATF4) through a mechanism that relies upon unique features in its 5' untranslated region [54].

Positive_regulation (induction) of ATF4

9) Confidence 0.31 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2527015 Disease Relevance 0.42 Pain Relevance 0.03

Figure 3 (Panel A) shows an increase in the level of nuclear ATF4 in NHBE cells in response to CS treatment at 4 hrs post-exposure which diminishes by 7 hrs.

Positive_regulation (increase) of ATF4

10) Confidence 0.27 Published 2008 Journal BMC Cancer Section Body Doc Link PMC2527015 Disease Relevance 0.24 Pain Relevance 0

Several other redox-sensitive genes were upregulated after short-term exposure to the high concentration of curcumin, like AREG, ATF4, EGR1, FGFR1 (Table 2) [44].

Positive_regulation (upregulated) of ATF4

11) Confidence 0.25 Published 2004 Journal J Carcinog Section Body Doc Link PMC421747 Disease Relevance 0.17 Pain Relevance 0.05

Calcium/calmodulin-dependent protein kinase IV, the cAMP-responsive-element binding protein activating enzyme, was also activated by 2,3,7,8-tetrachlorodibenzo-p-dioxin in an activity-dependent manner.

Positive_regulation (activated) of cAMP-responsive-element binding protein

12) Confidence 0.10 Published 2008 Journal J. Neurochem. Section Abstract Doc Link 17973980 Disease Relevance 0.14 Pain Relevance 0.49

Furthermore, TTX and MK801 differentially affected the association of AhR and its transcriptional co-activator cAMP-responsive-element binding protein with the cytochrome P450 1A1 (cyp1A1) gene enhancer.

Positive_regulation (co-activator) of cAMP-responsive-element binding protein associated with tetrodotoxin

13) Confidence 0.07 Published 2008 Journal J. Neurochem. Section Abstract Doc Link 17973980 Disease Relevance 0.15 Pain Relevance 0.53

In addition, its action via progesterone response element cis-elements, PR appeared to inhibit trans-activation of a nuclear factor-kappaB-responsive element, further suppressing RANTES expression.

Positive_regulation (trans-activation) of factor-kappaB-responsive

14) Confidence 0.02 Published 2002 Journal J. Clin. Endocrinol. Metab. Section Abstract Doc Link 12050207 Disease Relevance 0.30 Pain Relevance 0.26

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