Gene interactions and pathways from curated databases and text-mining

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Pathways - manually collected, often from reviews:

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

Studies that report less than 10 interactions are marked with *

Text-mined interactions from Literome

Jeong et al., J Biol Chem 2005 : A novel NF-kappaB pathway involving IKKbeta and p65/RelA Ser-536 phosphorylation results in p53 Inhibition in the absence of NF-kappaB transcriptional activity
Gilmore , Oncogene 2006 : NF-kappaB signaling is primarily regulated by inhibitor kappaB ( IkappaB ) proteins and the IkappaB kinase complex through two major pathways : the canonical and non-canonical NF-kappaB pathways
Fazal et al., J Biol Chem 2009 : The effect of cofilin-1 depletion on NF-kappaB activity and ICAM-1 expression occurred downstream of IkappaBalpha degradation and was a result of impaired RelA/p65 nuclear translocation and consequently, RelA/p65 binding to DNA
Wu et al., J Cell Biochem 2010 : Activation of NF-kappaB by TNFalpha enhances p50/RelA binding to the NF-kappaB binding sites
Liden et al., J Biol Chem 1997 : Glucocorticoids inhibit NF-kappaB signaling by interfering with the NF-kappaB transcription factor RelA
Donepudi et al., J Immunol 2001 (Mast-Cell Sarcoma) : Moreover, exposure of P815 tumor cells to a cell-permeable peptide that selectively inhibits NF-kappaB activation by blocking the activation of the IkappaB-kinase complex was found to inhibit the L-PAM induced B7-1 mRNA accumulation, indicating that NF-kappaB activation is essential for the L-PAM induced B7-1 gene expression
Park et al., J Biol Chem 2003 : Heat shock protein 27 association with the I kappa B kinase complex regulates tumor necrosis factor alpha induced NF-kappa B activation
Matsushima et al., J Exp Med 2001 : Both nuclear factor (NF)-kappaB inducing kinase ( NIK ) and inhibitor of kappaB (IkappaB) kinase ( IKK ) have been implicated as essential components for NF-kappaB activation in response to many external stimuli
Thomas et al., Immunol Cell Biol 2006 : We found that NIT-1 cells are defective in the activation of nuclear factor-kappaB (NFkappaB) as a result of functionally deficient RelA activity, because overexpression of RelA protected NIT-1 cells from apoptosis
Rosato et al., J Biol Chem 2010 (Leukemia) : LBH-589 triggered p65/RelA activation, NF-kappaB dependent induction of Mn-SOD2, and ROS elimination
O'Mahony et al., J Biol Chem 2004 (Cell Transformation, Viral) : Human T-cell lymphotropic virus type 1 tax induction of biologically Active NF-kappaB requires IkappaB kinase-1 mediated phosphorylation of RelA/p65
Sasaki et al., Clin Cancer Res 2001 (Lymphatic Metastasis...) : There was a significant correlation between NF-kappaB activation ( nuclear translocation of RelA ) and expression of urokinase-type plasminogen activator, an invasion related factor and target of NF-kappaB in tumor cells ( rho = 0.393 ; P = 0.0013 )
Aggarwal et al., Mol Pharmacol 2006 (Neoplasm Metastasis) : Curcumin also suppressed NF-kappaB reporter activity induced by tumor necrosis factor receptor (TNFR)1, TNFR2, NF-kappaB inducing kinase, IkappaB kinase complex (IKK) , and the p65 subunit of NF-kappaB
Song et al., Proc Natl Acad Sci U S A 2006 : Because IRAK1 is upstream of TRAF6 in IL-1 activation of NF-kappaB, the potential role of IRAK1 in LMP1 mediated NF-kappaB activation through TRAF6 and inhibitor of kappaB (IkappaB) kinase ( IKK ) was initially investigated
Boersma et al., Science signaling 2008 : Transcriptional activation by NF-kappaB and chromatin remodeling by inhibitor of kappaB (IkappaB) kinase complex ( IKK ) have been linked to recall and reconsolidation of conditioned fear memories in the mammalian central nervous system
Duran et al., EMBO J 2003 : Essential role of RelA Ser311 phosphorylation by zetaPKC in NF-kappaB transcriptional activation
Channavajhala et al., J Biol Chem 2003 (MAP Kinase Signaling System) : This inhibition is specific to Cot, because Ras induced ERK and IkappaB kinase induced NF-kappaB activation are not significantly affected by hKSR-2 co-expression
Adli et al., J Biol Chem 2006 (Inflammation) : NF-kappaB activation downstream of lipopolysaccharide or cytokine stimulation is controlled by the IkappaB kinase complex , which contains IKKalpha and IKKbeta
Tucker et al., J Immunol 2007 : These findings demonstrate a key role for NF-kappaB2 in the regulation of RelA activation and suggest overlap in the function of NF-kappaB members in canonical and noncanonical pathway signaling
Wong et al., Clin Immunol 2006 : Fas ( CD95 ) ligation inhibits activation of NF-kappa B by targeting p65-Rel A in a caspase dependent manner
Mortaz et al., Biochem Pharmacol 2005 : We thus propose that the anti-inflammatory effects of ASA in mast cells are due to suppression of IkappaB kinase activity, thereby inhibiting subsequent phosphorylation and degradation of IkappaB-alpha, activation of NF-kappaB , and transcription of proinflammatory cytokines
Stark et al., Mol Cell Biol 2005 : Nucleolar sequestration of RelA ( p65 ) regulates NF-kappaB-driven transcription and apoptosis
Haddad et al., J Pharmacol Exp Ther 2002 (Inflammation...) : Whereas selective inhibition of PDEs 1, 3, and 4, by the action of 8-methoxymethyl-3-isobutyl-1-methylxanthine, amrinone, and rolipram, respectively, exhibited a tendency to augment the translocation of NF-kappaB ( 1 ) ( p50 ), RelA ( p65 ), RelB ( p68 ), and c-Rel ( p75 ), selective blockade of PDE 5, 6, and 9, by the action of 4- [ [ 3',4'- ( methylenedioxy ) benzyl ] amino ] -6-methoxyquinazoline and zaprinast, attenuated lipopolysaccharide-endotoxin (LPS) mediated NF-kappaB translocation
Kim et al., Mol Cancer Res 2008 (Glioma) : Here, we report that the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin ( 17-AAG ) blocks MMP-9 secretion and that HA-induced nuclear factor-kappaB (NF-kappaB) activation is mediated by IkappaB kinase , which phosphorylates the NF-kappaB inhibitor IkappaBalpha and promotes its degradation
Anest et al., Nature 2003 : NF-kappaB is a principal transcriptional regulator of diverse cytokine mediated processes and is tightly controlled by the IkappaB kinase complex ( IKK-alpha/beta/gamma )
Watanabe et al., Proc Natl Acad Sci U S A 2004 (MAP Kinase Signaling System) : The NF-kappaB translocation dependent pathway involves NF-kappaB inducing kinase-IkappaB kinase beta/gamma dependent phosphorylation and degradation of IkappaBalpha, whereas the NF-kappaB translocation independent pathway involves mitogen activated protein kinase ( MAPK ) /extracellular signal regulated kinase kinase kinase 1-dependent activation of MAPK kinase 3/6-p38 MAPK pathway
Ragheb et al., Biochem Biophys Res Commun 2008 (Disease Models, Animal...) : Interestingly, IkappaB-kinase beta (IKKbeta) dependent NF-kappaB was activated in hepatocytes from the fructose fed hamster as an indication for PKC activation
Huang et al., J Biol Chem 2004 : Activation of NFkappaB requires the activity of IkappaB kinase , a kinase complex that contains two catalytic subunits, IKKalpha and IKKbeta, and a non-enzymatic regulatory subunit, IKKgamma
Jue et al., J Korean Med Sci 1999 (Arthritis, Rheumatoid) : Aspirin and sodium salicylate inhibit activation of NF-KB by blocking IkappaB kinase , a key enzyme in NF-kappaB activation
Gil et al., Oncogene 2000 : Activation of NF-kappa B by the dsRNA dependent protein kinase, PKR involves the I kappa B kinase complex
Zhang et al., PloS one 2006 : Both phenotypes are rescued by injection of RNA encoding the anti-apoptotic protein Bcl-xL ; Bcl-xL 's effects are dependent upon IkappaB kinase mediated activation of the bipartite transcription factor NF-kappaB
Tanabe et al., Journal of neuroinflammation 2010 (Glioma) : Wedelolactone, an inhibitor of IkappaB kinase , suppressed both TNF-alpha induced IkappaB phosphorylation and NFkappaB phosphorylation at Ser 536 and Ser 468
Park et al., J Biol Chem 2004 : Fas associated factor-1 inhibits nuclear factor-kappaB (NF-kappaB) activity by interfering with nuclear translocation of the RelA ( p65 ) subunit of NF-kappaB
Uhlik et al., J Biol Chem 1998 : NF-kappaB inducing kinase and IkappaB kinase participate in human T-cell leukemia virus I Tax mediated NF-kappaB activation
Shultz et al., J Interferon Cytokine Res 2007 : Activation of NF-kappaB requires the inhibitor of kappaB (IkappaB) kinase ( IKK) complex, which is made up of two functional kinases, IKKalpha and IKKbeta, and the scaffolding protein IKKgamma
Geisler et al., Gastroenterology 2007 (Drug-Induced Liver Injury) : RelA/p65 is essential for TNF induced NF-kappaB activation in adult hepatocytes
Nitta et al., Cell Signal 2003 (Cell Transformation, Viral) : Addition therein of RelA, an active subunit of NF-kappaB, restored the NF-kappaB activation and cell death induction by LMP1, but RelA alone did not induce cell death
Wong et al., Shock 2002 (Hyperoxia...) : Hyperoxia prolongs tumor necrosis factor-alpha mediated activation of NF-kappaB : role of IkappaB kinase
Khoshnan et al., J Neurosci 2004 (Nerve Degeneration) : In inducible PC12 cells and in HD transgenic mice, mutant Htt activates the IkappaB kinase complex (IKK) , a key regulator of NF-kappaB
Lee et al., Biochem Pharmacol 2003 : Further analysis revealed that manassantins A and B dose-dependently suppressed not only the induced NF-kappaB activation by overexpression of RelA/p65 , but also transactivation activity of RelA/p65
Teruya et al., BMC microbiology 2007 : Collectively, these results suggest that L. pneumophila induces activation of NF-kappaB through an intracellular signaling pathway that involves NF-kappaB inducing kinase and IkappaB kinase , leading to IL-8 gene transcription, and that hsp90 acts as a crucial regulator in L. pneumophila induced IL-8 expression, presumably contributing to immune response in L. pneumophila
Fan et al., J Biol Chem 2009 (MAP Kinase Signaling System...) : The ability of Src to enhance SF stimulation of NF-kappaB activity was due, in part, to its ability to stimulate Akt and IkappaB kinase activity ; and Src mediated stimulation of NF-kappaB was due , in part, to a Rac1/MKK3/6/p38 pathway and was Akt dependent
Hehner et al., J Immunol 1999 : The antiinflammatory sesquiterpene lactone parthenolide inhibits NF-kappa B by targeting the I kappa B kinase complex
Fan et al., J Biol Chem 2009 : Overexpression of a RelA mutant with an arginine substitution for the lysine 195 residue dramatically inhibits RelA polyubiquitination and induces a stronger NF-kappaB activation compared with the wild type
Prajapati et al., J Biol Chem 2004 : Protein phosphatase 2Cbeta association with the IkappaB kinase complex is involved in regulating NF-kappaB activity
Wang et al., Cancer Cell 2007 (Carcinoma, Squamous Cell...) : LZAP directly bound to RelA, impaired serine 536 phosphorylation of RelA, increased HDAC association with RelA , inhibited basal and stimulated NF-kappaB transcriptional activity, and was found at the promoter of selective NF-kappaB-responsive genes
Zamanian-Daryoush et al., Mol Cell Biol 2000 : NF-kappaB activation by double-stranded-RNA activated protein kinase ( PKR ) is mediated through NF-kappaB inducing kinase and IkappaB kinase
Lamkanfi et al., J Biol Chem 2004 (MAP Kinase Signaling System) : We demonstrate that caspase-1 interacts with RIP2 and that dominant negative forms of RIP2 and IkappaB kinase complex-beta inhibit caspase-1 mediated NF-kappaB activation
Johannessen et al., J Gen Virol 2003 : Mutation of the TATA box had no effect on TNFalpha- or RelA/p65 mediated induction of NFkappaB-responsive promoters, indicating a specific st-ag effect on hTAF ( II ) 130/135
O'Shea et al., Biochem J 2010 : Thr435 phosphorylation regulates RelA ( p65 ) NF-kappaB subunit transactivation
Tudhope et al., J Immunol 2007 : The role of IkappaB kinase 2, but not activation of NF-kappaB , in the release of CXCR3 ligands from IFN-gamma stimulated human bronchial epithelial cells
Kim et al., Mol Pharmacol 2008 (Inflammation...) : Here, we demonstrate that the novel small-molecule benzoxathiole 6,6-dimethyl-2- ( phenylimino ) -6,7-dihydro-5H-benzo- [ 1,3 ] oxathiol-4-one ( BOT-64 ) inhibits NF-kappaB activation with an IC ( 50 ) value of 1 muM by blocking inhibitory kappaB(IkappaB) kinase beta ( IKKbeta ), and suppresses NF-kappaB regulated expression of inflammatory genes in lipopolysaccharide (LPS) activated RAW 264.7 macrophages
Rebholz et al., J Invest Dermatol 2008 (MAP Kinase Signaling System) : The biphasic NF-kappaB response was strictly dependent on the transactivating subunit RelA , as demonstrated by keratinocytes lacking RelA
Jijon et al., Cell Signal 2004 : These data demonstrate for the first time the presence of an IKKgamma independent NIK/p38 MAPK dependent signaling pathway that activates NF-kappaB and induces pro-inflammatory gene expression through RelA phosphorylation
Liu et al., J Biol Chem 2006 : Phosphorylation of IkappaB-beta enhances its association with p65/RelA causing an increase in NF-kappaB DNA binding activity
Zhang et al., Ann Surg Oncol 2007 (Adenocarcinoma...) : There was a positive correlation between NF-kappaB activation ( nuclear translocation of RelA ) and tumor clinicopathological features such as tumor grade, including T stages, N stages, and tumor, node, metastasis system stages, smoking status, and age
Pyo et al., J Neurosci Res 2010 (Neuroblastoma) : Suppression of NF-kappaB activation using transfection of the superrepressive mutant form of IkappaBalpha ( mIkappaBalpha ) inhibited nuclear RelA expression in both types of SOD1 cells, which increased glutamate excitotoxicity in wtSOD1 cells but not in mtSOD1 cells
Lederer et al., J Immunol 1996 : We demonstrate that IL-1 and TNF induce rapid nuclear translocation of p65(RelA) in T cell clones, whereas TCR induced NF-Kappa B activation in Th1 cells is delayed and may be longer in duration
Yang et al., J Biol Chem 2003 : The data show that RelA regulation of NF-kappaB-IkappaBalpha complex formation is IkappaBalpha phosphorylation dependent and that IkappaBalpha/NF-kappaB binding is dynamic and determined by concentration of the subunits
Eickhoff et al., J Biol Chem 2004 (Cytomegalovirus Infections) : A stable inhibitor of NF-kappaB ( IkappaB ) reverses the RICK inhibitory effect, and activation of NF-kappaB by IkappaB kinase beta expression is inhibitory to HCMV, demonstrating that NF-kappaB activation is part of a potent anti-HCMV response
Moon et al., Free Radic Biol Med 2006 : Results were supported by NF-kappaB activation as judged by reduced IkappaBalpha degradation and increased nuclear translocation of p65/RelA with LPS stimulation, serum deprivation, and PrxII deletion
Zingarelli et al., FASEB J 2002 (Myocardial Infarction...) : These events were preceded by degradation of inhibitor kappaBalpha ( IkappaBalpha ), activation of IkappaB kinase complex (IKK) and c-Jun-NH2-terminal kinase (JNK), and subsequently activation of nuclear factor-kappaB (NF-kappaB) and activator protein 1 (AP-1) as early as 15 min after reperfusion
Hagemann et al., J Exp Med 2008 (Neoplasms) : We show that macrophages are polarized via interleukin (IL)-1R and MyD88 to an immunosuppressive `` alternative '' phenotype that requires IkappaB kinase beta mediated NF-kappaB activation
Wang et al., J Neurosci 2010 : We found that downregulating the expression of RelA/p65 subunit of NF-kappaB or inhibiting NF-kappaB activity by overexpression of mutated form of IkappaB ( inhibitor kappaB ), which is resistant to proteolytic degradation and thus constitutively keeps NF-kappaB inactive in the cytoplasma, impeded the formation of AChR clusters in cultured C2C12 muscle cells stimulated by Agrin
Chan et al., Biochem Biophys Res Commun 2005 : Tpl2/COT1 was shown to participate in CD40 signaling based on the ability of a catalytically inactive mutant to suppress CD40 mediated IkappaB kinase activation and induction of NFkappaB-responsive promoters, without affecting signaling by TNF