Gene interactions and pathways from curated databases and text-mining

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PTGS2 — TP53

Protein-Protein interactions - manually collected from original source literature:

Studies that report less than 10 interactions are marked with *

Text-mined interactions from Literome

Zahner et al., J Biol Chem 2002 : These data suggest that COX-2 inhibits mesangial cell proliferation by a novel mechanism that is independent of prostaglandin synthesis, but involves p53 , p21 ( cip-1 ), and p27 ( kip-1 )
Han et al., EMBO J 2002 : We also found that p53 induced Cox-2 expression results from p53 mediated activation of the Ras/Raf/MAPK cascade, as demonstrated by suppression of Cox-2 induction in response to p53 by dominant negative Ras or Raf1 mutants ... Together, these results demonstrate that Cox-2 is induced by p53 mediated activation of the Ras/Raf/ERK cascade, counteracting p53 mediated apoptosis
Shigemasa et al., Int J Oncol 2003 (Adenocarcinoma...) : COX-2 overexpression in ovarian cancer cells might partly be caused by dysfunctional p53
Han et al., Mech Ageing Dev 2004 (Arthritis, Rheumatoid...) : The selective COX-2 inhibitor, NS-398, can inhibit the senescence associated increases of COX-2, PGE ( 2 ), p53 and MMP-1 expression, and the senescence associated decreases of PCNA, TIMP-1 and procollagen expression
Lee et al., Head Neck 2004 (Carcinoma, Squamous Cell...) : Effects of p53 or p27 overexpression on cyclooxygenase-2 gene expression in head and neck squamous cell carcinoma cell lines ... The effects of p53 or p27 gene transfer on COX-2 expression by adenoviral vector and the combined effects of p53 or p27 gene transfer and COX-2 inhibitor exposure on the proliferation of cancer cells were investigated in head and neck squamous cell carcinoma ( HNSCC ) cell lines ... Overexpression of p53 markedly downregulated the transcription of COX-2, but the overexpression of p27 did not affect COX-2 levels in HNSCC cell lines
Kim et al., Toxicological sciences : an official journal of the Society of Toxicology 2005 : In addition, 2,2',4,6,6'-PeCB stimulated COX-2 induction was reduced by the specific MAPK kinase ( MEK ) inhibitor, PD98059, and in p53-deficient cells, implying that COX-2 induction requires the activation of ERK1/2 MAPK and p53
Liu et al., J Biol Chem 2005 (Anoxia...) : To elucidate the effects of COX-2 on p53 in response to hypoxia, we transfected the COX-2 gene into the p53 positive, COX-2 negative MDA-PCa-2b human prostate cancer cell line ... Overexpression of COX-2 abrogated hypoxia induced p53 phosphorylation and promoted the binding of p53 to Mdm2 protein in hypoxic cells ... Finally, forced expression of COX-2 suppressed both basal and hypoxia induced p53 transcriptional activity, and this effect was mimicked by the addition of PGE2 to wild-type cells ... These results demonstrated a role for COX-2 in the suppression of hypoxia induced p53 activity via both direct effects and indirect modulation of Mdm2 activity
Corcoran et al., Oncogene 2005 (Breast Neoplasms...) : Here we report that the tumor suppressor p53 upregulates COX-2 expression and that COX-2 can in turn inhibit p53 dependent transcription ... Expression of exogenous COX-2 in p53 wild-type cells does not affect the cytoplasmic or nuclear levels of p53 , suggesting that COX-2 may not affect p53 turnover or subcellular localization ... Thus, p53 upregulates COX-2 and COX-2 in turn appears to negatively affect p53 activity via mechanisms that could involve physical interactions between COX-2 and p53 ... Based on our results, we propose that p53 dependent upregulation and activation of COX-2 appear to be yet another novel mechanism by which p53 could abate its own growth-inhibitory and apoptotic effects
Choi et al., Biochem Biophys Res Commun 2005 : COX-2 regulates p53 activity and inhibits DNA damage induced apoptosis ... We have previously shown that p53 induces cyclooxygenase-2 (COX-2) expression and COX-2 inhibits p53- or genotoxic stress induced apoptosis
Lee et al., Int J Gynecol Cancer 2006 (Adenocarcinoma...) : p53 may be responsible for the regulation of COX-2 expression
Ogino et al., Neoplasia (New York, N.Y.) 2006 (Colorectal Neoplasms) : Cyclooxygenase-2 (COX-2) overexpression and mutations of p53 ( a known COX-2 regulator ) are inversely associated with microsatellite instability-high ( MSI-H ) and CpG island methylator phenotype ( CIMP ) characterized by extensive promoter methylation, is associated with MSI-H
Atula et al., Oncol Rep 2006 (Carcinoma, Squamous Cell...) : COX-2 expression is suppressed by the wild-type but not by the mutant tumour suppressor gene TP53
Lim et al., Yonsei Med J 2007 (Adenocarcinoma...) : Existing evidence suggests that COX-2 expression is normally suppressed by wild-type p53 but not mutant p53, suggesting that loss of p53 function may result in the induction of COX-2 expression
Lin et al., J Cell Biochem 2008 (Head and Neck Neoplasms...) : Resveratrol induced nuclear COX-2 accumulation was dependent upon ERK1/2 activation, but not p53 activation ... Activation of p53 and p53 dependent apoptosis were blocked by the COX-2 inhibitor, NS398, and by transfection of cells with COX-2-siRNA ... Resveratrol-inducible nuclear accumulation of COX-2 is essential for p53 activation and p53 dependent apoptosis in these cancer cells
Hermanova et al., Eur J Gastroenterol Hepatol 2008 (Adenocarcinoma...) : The p53 dependent upregulation of COX-2 was proposed to be another mechanism by which p53 could abate its own growth-inhibitory and apoptotic effects
Zdanov et al., Biogerontology 2009 : p53 and ATF-2 partly mediate the overexpression of COX-2 in H ( 2 ) O ( 2 ) -induced premature senescence of human fibroblasts
Duarte et al., Cancer Lett 2009 (Carcinoma, Non-Small-Cell Lung...) : Role of p53 in the induction of cyclooxygenase-2 by cisplatin or paclitaxel in non-small cell lung cancer cell lines ... Therefore, we suggest that induction of COX-2 by cisplatin in NSCLC cell lines is dependent on p53
Choi et al., Biochim Biophys Acta 2009 : The p53 interacting region was critical for COX-2 mediated inhibition of p53 DNA binding and transcriptional activity as well as p53- and genotoxic stress induced apoptosis ... In addition, an active site mutant of COX-2 ( S516Q ) as well as wild-type COX-2 potently inhibited p53 transcriptional activity and genotoxic stress induced apoptosis
Gesser et al., Inflamm Res 2011 (Psoriasis) : The expression of p-p53 ( S15 ) was induced simultaneously with the inhibition of Cox-2
Park et al., Mol Carcinog 2012 (Colonic Neoplasms...) : HFD feeding increased tumor tissue levels of Ki67, cyclin A, cyclin D1, CDK2, Bcl-xL, and Bcl-2 ; reduced p53 levels and TUNEL positive apoptotic cells ; increased the levels of CD45, CD68, CD31, VEGF, P-VEGF receptor-2, iNOS, and COX-2 as well as hemoglobin content ; and increased the levels of HIF-1a, P-STAT3-Y705, P-STAT3-S727, P-I?B-a, P-p65, p65, P-c-Jun, P-Akt, P-ERK1/2, P-p38, and P-SAPK/JNK
Katkoori et al., Biotech Histochem 2013 (Prostatic Neoplasms) : Reduced COX-2 expression was found with decreased p53 in LNCaP and PC-3 cells that were exposed to = 20 µM of celecoxib for 72 h, but COX-2 expression was increased in DU145 cells
Dagouassat et al., Am J Respir Crit Care Med 2013 (Pulmonary Disease, Chronic Obstructive) : PGE2 acts either in a paracrine or autocrine fashion by a pathway involving EP2 and EP4 prostaglandin receptors, cyclooxygenase-2 dependent reactive oxygen species production and signaling, and consecutive p53 activation