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RELA — TP53
Pathways - manually collected, often from reviews:
-
OpenBEL Selventa BEL large corpus:
RELA
→
Complex of CREBBP-TP53
(decreases, CREBBP/TP53 Activity)
Wadgaonkar et al., J Biol Chem 1999*
Evidence: Nuclear competition for limiting amounts of CBP provides a novel mechanism for altering the balance between the expression of NF-kappaB-dependent proliferation or survival genes and p53-dependent genes
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FastForward regulation:
RELA
→
TP53
(transcriptional regulation, unknown)
Kirch et al., Oncogene 1999*, Pei et al., J Biol Chem 1999*, Qin et al., Mol Endocrinol 2002*
Evidence: DNABINDING
-
FastForward regulation:
RELA
→
TP53
(transcriptional regulation, unknown)
Qin et al., Mol Endocrinol 2002*
Evidence: DNABINDING
Text-mined interactions from Literome
Webster et al., Mol Cell Biol 1999
:
Moreover, endogenous, tumor necrosis factor alpha activated
NF-kappaB will
inhibit endogenous wild-type
p53 transactivation
Kirch et al., Oncogene 1999
:
Expression of human
p53 requires synergistic activation of transcription from the p53 promoter by AP-1,
NF-kappaB and Myc/Max
Park et al., Nephron 1999
:
Decrease in
NF-kappaB activity and
activation of
p53 induced by inhibition of interaction with ECM play roles in anoikis in SV-40 transformed collecting duct cells
Nakai et al., J Neurochem 2000
:
The present results provide additional support for the view that
NF-kappaB activation
contributes to c-Myc and
p53 induction and subsequent apoptosis in an excitotoxic model of Huntington 's disease
Shao et al., Oncogene 2000
(Adenocarcinoma...) :
Overexpression of the wild-type
p53 gene
inhibits NF-kappaB activity and synergizes with aspirin to induce apoptosis in human colon cancer cells ... In this study, to better understand the mechanism responsible for the p53 mediated apoptosis, the
effect of wild-type
p53 ( wt-p53 ) gene transfer on nuclear expression of
NF-kappaB was determined in human colon cancer cell lines ... A Western blot analysis of nuclear extracts demonstrated that
NF-kappaB protein levels in the nuclei were
suppressed by the transient expression of the
wt-p53 in a dose dependent manner
Haddad et al., Biochem Biophys Res Commun 2000
:
Sulfasalazine, a potent and specific inhibitor of
NF-kappaB , induced Bax at the expense of Bcl-2, in a
p53 dependent manner
Ryan et al., Nature 2000
:
Here we show that induction of
p53 causes an activation of
NF-kappaB that correlates with the ability of p53 to induce apoptosis ...
Activation of
NF-kappaB by
p53 was distinct from that mediated by tumour-necrosis factor-alpha and involved MEK1 and the activation of pp90rsk ... Inhibition of MEK1 blocked
activation of
NF-kappaB by
p53 and completely abrogated p53 induced cell death
Ikeda et al., Biochem Biophys Res Commun 2000
:
However, we found that the inhibition by RelA of p53 transcriptional activity is not completely restored by CBP/p300 overexpression and that a
p53 mutant can not
suppress RelA activity despite of its ability to bind CBP/p300
Ros et al., Hepatology 2001
(Carcinoma, Hepatocellular...) :
Because
p53 is up-regulated by TNF-alpha in an
NF-kappaB dependent manner and the Mdr1b promoter contains a p53 binding site, we used liver cells expressing a dominant negative p53 to show that TNF-alpha up-regulation of Mdr1b is independent of functional p53
Zhang et al., J Biol Chem 2001
:
Inhibition of cell cycle progression by the novel cyclophilin ligand sanglifehrin A is mediated through the
NFkappa B-dependent activation of
p53
Liao et al., Zhonghua Zhong Liu Za Zhi 2001
(Nasopharyngeal Neoplasms) :
Induction of
p53 expression could be
blocked by phosphorothiate analogs of antisense oligonucleotides to NF-kappa B p65 and LMP1, but not by
NF-kappa B p50
Tergaonkar et al., Cancer Cell 2002
:
IKK2 mediated effects required its kinase function and were abrogated by coexpression of the dominant negative IkappaBalphaM, implying a
role for
NFkappaB in blocking chemotherapy induced
p53 and cell death
de Erausquin et al., Mol Pharmacol 2003
:
Treatment of mesencephalic cultures with alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ( AMPA ) resulted in a number of changes that occurred selectively in dopaminergic neurons, including persistent elevation in intracellular Ca ( 2+ ) monitored with Fura-2, and a significant increase in intramitochondrial oxidation of dihydrorhodamine 123, probably associated with transient increase of mitochondrial permeability, cytochrome c release, nuclear translocation of
NF kappa B , and transcriptional
activation of the oncogene
p53
Shimada et al., Carcinogenesis 2003
(Prostatic Neoplasms) :
Inhibition of p38 or
NFkappaB resulted in suppression of
p53 induction and apoptosis
Rocha et al., Mol Cell Biol 2003
:
p53 represses cyclin D1 transcription through down regulation of Bcl-3 and
inducing increased association of the p52
NF-kappaB subunit with histone deacetylase 1
Lagunoff et al., Int Rev Immunol 2003
:
Virally encoded genes inhibit the activation of caspase-8 by the TNF receptor and Fas ; activate
NF-kappaB to
increase expression of antiapoptotic genes ; inhibit interferon response ; bind to
p53 , thereby blocking p53 dependent apoptosis ; and interact with other pro- and antiapoptotic cellular genes
Culmsee et al., J Neurosci 2003
(Brain Ischemia) :
In cultured neurons DNA damaging compounds
induced activation of
p53 , whereas
NF-kappaB activity declined significantly
Guo et al., Mol Cell Biol 2004
:
We found that ( i ) p19(Arf) or p53 deficiency led to a significant increase in PI 3-kinase activity, which in turn upregulated RhoA and Rac1 activities ; ( ii ) deletion of p19Arf or p53 led to an increase in cell growth rate that was in part dependent on RhoA, Rac1, and Cdc42 activities ; ( iii ) p19(Arf) or
p53 deficiency
caused an enhancement of the growth related transcription factor
NF-kappa B and cyclin D1 activities that are partly dependent on RhoA or Cdc42 but not on Rac1 ; ( iv ) forced expression of the activating mutants of Rac1, RhoA, or Cdc42 caused a hyperproliferative phenotype of the p19Arf ( -/- ) and p53 ( -/- ) cells and promoted transformation of both cells ; ( v ) RhoA appeared to contribute to p53 regulated cell proliferation by modulating cell cycle machinery, while hyperactivation of RhoA further suppressed a p53 independent apoptotic signal ; and ( vi ) multiple pathways regulated by RhoA, including that of Rho-kinase, were required for RhoA to fully promote the transformation of p53 ( -/- ) cells
Aleyasin et al., J Neurosci 2004
:
NF-kappaB inhibition also
reduced p53 transcripts and
p53 activity as measured by the p53-inducible messages, Puma and Noxa, implicating the p53 tumor suppressor in the mechanism of NF-kappaB mediated neuronal death ... Importantly,
p53 expression still induces death in the
presence of
NF-kappaB inhibition, indicating that p53 acts downstream of NF-kappaB
Bohuslav et al., J Biol Chem 2004
:
p53 induces
NF-kappaB activation by an IkappaB kinase independent mechanism involving phosphorylation of p65 by ribosomal S6 kinase 1 ... Here we describe the novel molecular mechanism through which
p53 and DNA damaging agents
activate NF-kappaB ...
NF-kappaB induction by
p53 does not occur through classical activation of the IkappaB kinases and degradation of IkappaBalpha
Fujioka et al., J Biol Chem 2004
:
Consequently,
NF-kappaB dependent
p53 activity induced the expression of p53 regulated genes PUMA and p21 ( waf1 ) as well as apoptosis ... Importantly, lack of RelA, IKK, and p53 as well as expression of a dominant negative IkappaBalpha ( IkappaBalphaM ) inhibited
NF-kappaB dependent
p53 activation and apoptosis
Nasr et al., Oncogene 2005
(Leukemia-Lymphoma, Adult T-Cell...) :
PS-341 treatment of these cells stabilized IkappaBalpha, IkappaBbeta, IkappaBvarepsilon, p21, p27 and
p53 proteins and selectively
inhibited Rel-A DNA binding
NF-kappaB complexes
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
Hidaka et al., J Exp Clin Cancer Res 2005
(Neoplasms) :
To analyze whether p53 status mediates IL-8 expression, the
effect of wild-type
p53 ( wt-p53 ) gene transfer on activation of
NF-kappaB was determined in both cell lines ... In contrast, luciferase reporter studies indicated that transcriptional activity of
NF-kappaB is
suppressed by transfection of
wt-p53 ... These results show that
wt-p53 gene transfer
inhibits IL-8 production and
NF-kappaB transcription activity in cancer cells and suggest that constitutive IL-8 production in cancer cells is associated with mutation of p53
Jeong et al., Oncogene 2005
(Cell Transformation, Viral) :
Activated AKT regulates
NF-kappaB activation,
p53 inhibition and cell survival in HTLV-1 transformed cells ... Blocking AKT with the PI3K/AKT inhibitor LY294002 or AKT SiRNA prevented
NF-kappaB activation and
inhibition of
p53 ... We suggest that AKT plays a role in the activation of prosurvival pathways in HTLV-1 transformed cells, possibly through
NF-kappaB activation and
inhibition of
p53 transcription activity
El Eter et al., Can J Physiol Pharmacol 2005
(Reperfusion Injury) :
Moreover, PDTC pretreatment abolished
p53 expression and
inhibited NF-kappaB translocation ... These results clearly demonstrate that
NF-kappaB activation and pro-apoptotic protein
p53 induction are involved in gastric I/R injury
Scian et al., Mol Cell Biol 2005
(Disease Progression) :
Tumor derived
p53 mutants
induce NF-kappaB2 gene expression
Gurova et al., Proc Natl Acad Sci U S A 2005
(Carcinoma, Renal Cell) :
Induction of
p53 by these compounds does not involve genotoxic stress and is
mediated by suppression of
NF-kappaB activity ... The results demonstrate, in principle, the possibility to kill cancer cells selectively through simultaneous inhibition of
NF-kappaB and
activation of
p53 by a single small molecule and suggest anticancer applications for the well known antimalaria drug quinacrine
Ko et al., FEBS Lett 2006
:
These data suggest that
NF-kappaB-dependency of the PAF induced increase in VEGF expression is
due to decreased
p53 activity, which is reciprocally regulated by increased NF-kappaB activity
Kikuchi et al., Oncogene 2006
:
Ectopic expression of NF-kappaB decreased a half-life of p73alpha by increasing its ubiquitination levels, and thereby inhibiting the transcriptional activity as well as proapoptotic function of p73alpha, whereas
NF-kappaB had undetectable effects on
p53
Armstrong et al., Neoplasia (New York, N.Y.) 2006
(Brain Neoplasms...) :
Moreover,
p53 is
necessary for
NF-kappaB activation because cells with inactive p53 were resistant to NF-kappaB mediated cell death
Minsavage et al., J Pharmacol Exp Ther 2007
:
Thus, disruption of
p53/p90RSK mediated
NF-kappaB signaling and activation of ARE/EpRE pathways may be effective strategies to delineate mechanisms of action of BFA induced inflammation and cell death signaling in immortalized versus normal skin systems
Armstrong et al., Neoplasia (New York, N.Y.) 2006
(Neuroblastoma) :
Moreover,
p53 is
necessary for
NF-kappaB activation because cells with inactive p53 were resistant to NF-kappaB mediated cell death
Weisz et al., Cancer Res 2007
(Breast Neoplasms...) :
We now report that cancer associated mutant
p53 can
augment the induction of
nuclear factor kappaB (NFkappaB) transcriptional activity in response to the cytokine tumor necrosis factor alpha (TNFalpha) ... Analysis of human head and neck tumors and lung tumors reveals a close correlation between the presence of abundant mutant
p53 proteins and the constitutive
activation of
NFkappaB
Liang et al., Brain Res 2007
(Nerve Degeneration...) :
Blockade of NF-kappaB nuclear translocation with recombinant cell-permeable peptide NF-kappaB SN50 inhibited
NF-kappaB nuclear translocation and
p53 induction
Plesnila et al., Cell Death Differ 2007
(Brain Injuries...) :
Delayed neuronal death after brain trauma involves
p53 dependent inhibition of
NF-kappaB transcriptional activity ... Inhibition of
p53 activity
resulted in the concomitant increase in
NF-kappaB transcriptional activity and upregulation of NF-kappaB-target proteins, for example X-chromosomal linked inhibitor of apoptosis ( XIAP )
Pekar et al., Reproduction 2007
(Abnormalities, Multiple...) :
p53 regulates cyclophosphamide teratogenesis by controlling caspases 3, 8, 9 activation and
NF-kappaB DNA binding
Guzman et al., Blood 2007
(Leukemia, Myeloid, Acute) :
Molecular studies indicate the prevalent activities of DMAPT include induction of oxidative stress responses, inhibition of
NF-kappaB , and
activation of
p53
Mi et al., Mol Ther 2008
(Carcinoma, Non-Small-Cell Lung...) :
This Dox induced
NF-kappaB activation and subsequent chemoresistance is
dependent on expression of
p53
Lee et al., Int J Cancer 2008
(Carcinoma, Squamous Cell...) :
Greater modulation among HNSCC lines expressing low wt p53 than those over expressing mt p53 protein suggested that decreased
p53 expression might
enhance activation of
NF-kappaB , STAT3 and BCL-XL
Logunov et al., Oncogene 2008
(Cell Transformation, Neoplastic...) :
Cells incubated with media conditioned with different species of mycoplasma showed constitutive activation of
NF-kappaB and reduced
activation of
p53 , common characteristics of the majority of human tumor cells, with M. arginini having the strongest effect among the species tested
Kawauchi et al., Biochem Biophys Res Commun 2008
:
Activated
p53 induces
NF-kappaB DNA binding but suppresses its transcriptional activation ... Thus, activated
p53 may
suppress transcriptional activity of
NF-kappaB through inhibition of IKK and histone H3 kinase on DNA, suggesting a novel p53 mediated suppression system for tumorigenesis
Chen et al., J Immunol 2008
:
Proteasome inhibitors enhance TRAIL induced apoptosis through the intronic regulation of DR5 : involvement of
NF-kappa B and reactive oxygen species mediated
p53 activation
Rasmussen et al., Inflamm Res 2008
(Inflammation) :
We studied
NF-kappaB activation and the
induction of interleukin 8 (IL-8) and
p53 gene expression in an interleukin 1beta (IL-1beta) stimulated HepG2 cell line ...
NF-kappaB induced IL-8 and
p53 protein production was studied using specific siRNA, an IkappaB kinase 2 inhibitor, and mitogen activated protein kinase ( MAPK ) inhibitors
Króliczak et al., Acta biochimica Polonica 2008
(Neoplasms) :
Sp1 and
NFkappaB binding to the probes resembling their putative binding sites present in the S100A6 promoter was decreased in the
presence of wild type
p53
Tsoporis et al., J Biol Chem 2008
(Inflammation) :
These results demonstrate that S100A6 is induced by tumor necrosis factor-alpha via an
NF-kappaB dependent mechanism, serving a role in homeostasis to limit tumor necrosis factor-alpha induced apoptosis by regulating
p53 phosphorylation
Dey et al., Nat Rev Drug Discov 2008
(Neoplasms) :
Although drugs are being designed to selectively activate
p53 or
inhibit NF-kappaB , there is no concerted effort yet to deliberately make drugs that can simultaneously do both
Suzuki et al., Am J Respir Cell Mol Biol 2009
:
NF-kappaB inhibitors also
reduced p53 phosphorylation
Liu et al., J Immunol 2009
(Acute Lung Injury) :
These data demonstrate that
p53 regulates
NF-kappaB activity in inflammatory cells and suggest that modulation of p53 may have potential therapeutic benefits in acute inflammatory conditions, such as ALI
Rath et al., DNA Cell Biol 2009
(Lung Neoplasms) :
We show that expression of
wt-p53 from a recombinant adenovirus-p53 followed by treatment with 2-methoxyestradiol ( 2-ME ), an endogenous, nontoxic, estrogenic metabolite,
resulted in differential
NF-kappaB activation and inhibitor kappaB alpha ( IkappaB-alpha ) degradation in three different human lung cancer cell lines with different p53 phenotypes ... In contrast, either
adeno-p53 expression or 2-ME treatment
induced NF-kappaB activation in the p53 deleted H1299 cells, but H460 cells, containing wt-p53, did not show NF-kappaB activation under any of these conditions
Meylan et al., Nature 2009
(Adenocarcinoma...) :
Concomitant loss of
p53 ( also known as Trp53 ) and expression of oncogenic Kras ( G12D )
resulted in
NF-kappaB activation in primary mouse embryonic fibroblasts
Mangolini et al., Apoptosis 2010
(Polycystic Kidney, Autosomal Recessive) :
FC1-depletion also induced reduction in ERK1/2 kinase activation, upregulation of the pro-apoptotic protein
p53 and
activation of
NF-kappaB , a transcription factor which reduces apoptosis in many organs and tissues
Kamal et al., Bioorg Med Chem 2010
:
Therefore, the data generated suggests that these PBD conjugates activate
p53 and
inhibit NF-kappaB and thereby these compounds could be promising anticancer agents with better therapeutic potential for the suppression of tumours
Wang et al., Eur J Neurosci 2009
:
These results suggest that overstimulation of NMDA receptors can induce
NF-kappaB dependent expression of
p53
Schneider et al., Oncogene 2010
:
Experiments with knockout cells show that p65 and
p53 are both
required for enhanced
NF-kappaB activity during S-phase checkpoint activation involving ataxia-telangiectasia mutated and checkpoint kinase-1 ... Hence,
p53 is unexpectedly
necessary for
NF-kappaB mediated gene expression induced by atypical and classical stimuli
Li et al., Toxicological sciences : an official journal of the Society of Toxicology 2010
(Cell Transformation, Neoplastic) :
The repressive
effect of
NF-kappaB on
p53 by mot-2 is involved in human keratinocyte transformation induced by low levels of arsenite ... Together, the results suggest that the repressive
effect of
NF-kappaB on
p53 by mot-2 leads to genomic instability, which is involved in arsenite induced malignant transformation of human keratinocytes
Hong et al., Neuroscience bulletin 2010
(Brain Ischemia) :
In addition,
p53 disrupts
NF-kappaB binding to p300 and blocks NF-kappaB mediated survival signaling
Gudkov et al., J Clin Invest 2010
:
Progress in understanding differences in the mechanisms involved in the responses of normal and tumor cells to genotoxic stress has led to the development of new rational approaches to selective protection of normal cells, such as suppression of apoptosis by pharmacological inhibition of
p53 or
activation of
NF-kappaB
Johnson et al., Cancer Res 2011
:
Translocation of the NF-?B family member
RelA to mitochondria was
inhibited by
p53 by blocking an essential interaction with the HSP Mortalin
Ghose et al., PloS one 2011
(Huntington Disease) :
We conclude that ( i ) miR-125b and miR-150 target p53, which in turn regulates RelA/NFkB and miR-146a expressions ; ( ii ) reduced miR-125b and miR-150 expressions, increased p53 level and decreased
RelA/NFkB and miR-146a expressions originate from mutant HTT ( iii )
p53 directly or indirectly
regulates the expression of miR-146a
Fouad et al., Pak J Biol Sci 2011
(Necrosis) :
The regulation of
p53 expression is
mediated by the transcription factor
NF-kappaB
Sun et al., Mol Cell Biol 1995
:
Although a kappa B motif partially overlaps with this element and those genotoxic agents activate NF-kappa B, it does not play a major role in p53 genotoxic stress response :
NF-kappa B p65 expression did not induce significant p53 promoter activation, and NF-kappa B inhibitors ( N-acetyl cysteine and I kappa B alpha ) did not
inhibit genotoxic stress-inducible
p53 promoter activation
Wu et al., J Biol Chem 1994
:
NF-kappa B activation of
p53 ... Thus, we show that
NF-kappa B activates
p53 and that this activation is inducible by TNF-alpha ... Since NF-kappa B induction occurs as a response to stress and p53 arrests cells in G1/S, where repair may be initiated,
activation of
p53 by
NF-kappa B could be a mechanism by which cells can recover from stress
Hellin et al., Oncogene 1998
(Colonic Neoplasms) :
Under our conditions, the free radical scavengers NAC and PDTC were not able to block
NF-kappaB activation or
p53 induction , indicating that reactive oxygen intermediates were not involved in the cellular response to daunomycin stimulation
Taylor et al., Biochemistry (Mosc) 1998
(Acute-Phase Reaction...) :
iNOS expression requires the transcription factor
NF-kappaB and is
down-regulated by steroids, TGF-beta, the heat shock response,
p53 , and nitric oxide ( NO ) itself
Ravi et al., Cancer Res 1998
:
p53 mediated repression of nuclear factor-kappaB
RelA via the transcriptional integrator p300 ...
p53 mediated repression of
RelA is relieved by p300 overexpression and the increased RelA activity conferred by p53-deficiency is counteracted by either transactivation domain-deficient p300 fragments that bind RelA or a transdominant mutant of IkappaB alpha
Wadgaonkar et al., J Biol Chem 1999
:
Increased levels of the coactivator relieve
p53 mediated repression of
NF-kappaB activity and p65 mediated repression of p53 dependent gene expression