Identifiers
HUGO:TP53
tumor protein p53
HUGO:TP53, HGNC:11998, ENTREZ:7157, UNIPROT:P04637, GENECARDS:GC17M007565
HUGO:TP53, HGNC:11998, ENTREZ:7157, UNIPROT:Q9NP68
HUGO:TP53 HGNC:11998 ENTREZ:7157 UNIPROT:P04637
HUGO:TP53 HGNC:11998 ENTREZ:7157 UNIPROT:P04637 GENECARDS:TP53 REACTOME:69487 KEGG:7157 ATLASONC:P53ID88 WIKI:TP53
Maps_Modules
HMC:ACTIVATING_INVASION_AND_METASTASIS
EMT Senescence / EMT_REGULATORS
EMT Senescence / SENESCENCE
EMT Senescence / MITOCHONDRIA_OXIDATIVE_STRESS
HMC:SUSTAINING_PROLIFERATIVE_SIGNALLING
Cell Cycle DNA Repair / G1_S_CHECKPOINT
Cell Cycle DNA Repair / G2_M_CHECKPOINT
HMC:RESISTING_CELL_DEATH
HMC:DEREGULATING_CELLULAR_ENERGETICS
Regulated Cell Death / ANTIOXIDANT_RESPONSE
Regulated Cell Death / APOPTOSIS
Regulated Cell Death / STARVATION_AUTOPHAGY
Regulated Cell Death / DEATH_RECEPTOR_PATHWAYS
Regulated Cell Death / DNA_DAMAGE_RESPONSE
Regulated Cell Death / MOMP_REGULATION
Regulated Cell Death / RCD_GENES
Regulated Cell Death / PENTOSE_PHOSPHATE_PATHWAY
HMC:EVADING_GROWTH_SUPPRESSORS
Survival / MAPK
Survival / PI3K_AKT_MTOR
Survival / WNT_CANONICAL
Survival / WNT_NON_CANONICAL
References
PMID:21518799
p53 activates MIR200C
PMID:21483453
p53 activates microRNAs
PMID:21336307
p53 activates MIR34
PMID:17823410
PMID:6396087, PMID:21340684, PMID:20457558, PMID:20182602, PMID:20066118
NATURAL_KILLER
PMID:22754780, PMID:21764762
Wild-type p53, but not mutant p53 interacts with UDLPs promoters and induces UDLP2 and UDLP1 expression in tumor cells and increases tumor immunogenicity.
UDLPs activate NKG2D* signaling in NK cells.Induction of wtp53 expression in tumor cells leads to their enhanced recognition by primary NK cells in a NKG2D-dependent manner.
PMID:22102694
Activation of p53 by Nutlin3a resulted in upregulation of Mir34a/c expression and decreased ULBP2 expression in several tumor models (but not in the all models).
P53 is a nuclear P38 target.
PMID:20506250
PMID:10721693
PMID:19459846
References
mo_re6:( motility ) PMID:21084277 PMID:19945467 PMID:29435006
References
mo_re6:( motility ) PMID:21084277 PMID:19945467 PMID:29435006
References
mo_re22:( motility ) PMID:29435006
mo_re37:( motility ) PMID:18471976
mo_re20:( motility ) PMID:21053359 PMID:18471976 PMID:21084277 PMID:23178297 PMID:20609352 PMID:22073279 PMID:22970020 PMID:21811102 PMID:25139404 PMID:24403062 PMID:27526109 PMID:27222233
References
em_emtc_emtc_re427( EMT Senescence ):
PMID:12667443
p53 induces apoptosis by target gene regulation and transcription-independent signaling.
A fraction of induced p53 translocates to the mitochondria of apoptosing tumor cells. Targeting p53 to mitochondria is sufficient to launch apoptosis.
Evidence that p53 translocation to the mitochondria occurs in vivo in irradiatedthymocytes was shown.
Further, p53 can directly induce permeabilization of the outer mitochondrial membrane by forming complexes with the protective BCL2L1, resulting in cytochrome c release.
p53 binds to BCL2L1 via its DNA binding domain.
Tumor-derived transactivation-deficient mutants of p53 concomitantly lose the ability to interact with BCL2L1 and promote cytochrome c release.
em_emtc_emtc_re434( EMT Senescence ):
PMID:14963330
Cytosolic localization of endogenous p53 was necessary and sufficient for apoptosis.
p53 directly activated the pro-apoptotic BCL2 protein Bax in the absence of other proteins to permeabilize mitochondria and engage the apoptotic program.
em_emtc_emtc_re437( EMT Senescence ):
PMID:15077116
p53 has a direct signalling role at mitochondria in the induction of apoptosis
p53 interacts with the pro- apoptotic mitochondrial membrane protein Bak. Interaction of p53 with Bak causes oligomerization and thus activation of Bak and release of cytochrome c from mitochondria.
Formation of the p53???Bak complex coincides with loss of an interaction between Bak and the anti-apoptotic Bcl2-family member Mcl1.
These results are consistent with a model in which p53 and Mcl1 have opposing effects on mitochondrial apoptosis by interacting with, and modulating the activity of, the death effector Bak.
em_re1544( EMT Senescence ):
PMID:18281283
production of NF-kappaB2 p52 is not tumorigenic but predisposes mice to inflammatory autoimmune disease by repressing Bim expression
References
em_emtc_emtc_re275( EMT Senescence ):
PMID:9618481
-Smad4 transactivated the proximal p21 promoter 1.3-fold
-Smad2 transactivated the proximal p21 promoter 3-fold
-Smad2/4 transactivated the proximal p21 promoter 12-fold
-Smad3 transactivated the proximal p21 promoter 25-fold
-Smad3/Smad2 transactivated the proximal p21 promoter 40-fold
-Smad3/Smad4 transactivated the proximal p21 promoter 110-fold
-Smad2/Smad3/Smad4 transactivated the proximal p21 promoter 140-fold
Smad proteins act as Transcriptional Activators via functional interactions with the Transcription factor Sp1
PMID:12545156
Myc represses differentiation-induced p21 expression via Miz-1-dependent interaction with the p21 core promoter
Myc binds the p21 core promoter in vitro through interaction with Miz-1
Myc and Miz-1 interact with the p21 promoter in vivo
PMID:15155580
Snail regulates cell-cycle progression and survival:
Snail regulates components of the early to late G1 transition and the G1/S checkpoint.
Snail represses Cyclin D2 transcription and increases p21/Cip1 transcription.
PMID:17550342
SNAI2 induces p21CIP1 (CDKN1A) expression
PMID:23869868
PMID:23140366
p53 transactivate p21
PMID:11283614
Myc: an ubiquitous mediator of cell growth and proliferation
Myc can both activate and repress transcription, depending on the nature of associated factors
TGFB downregulates Myc to cause cell cycle arrest.
TGFB activates p15INK4B and/or p21CIP1 (inhibitor of CDKs) ==> CDK inhibition by TGFB
TGFB downregulates cdc25A (a phosphatase, activator of CDKs) ==> CDK inhibition by TGFB
PMID:2191300
Interaction of an NF-kappa B-like factor with a site upstream of the c-myc promoter.
PMID??:28536364
c-myc is transcriptionally upregulated by NF-??B
PMID:20027199
MYC induces DNA damage throuh an increase in ROS production, innapropriate DNA synthesis and abrogation of DNA repair
PMID:20713526
MYC supress the activity of anti-apoptotic BCL2 and BCLXL (BCL2L1) genes
PMID??:20713526
MYC in complex with CDK2 alone inhibit senescence through the inhibition of p16 and p21 expression as well as TERT and BMI1 expression increase. MYC in complex with CDK2 and p27KIP1 induces senescence through the expression increase of p16 and p21 as well as TERT and BMI1 expression decrease. WRN inhibit MYC induced senescence.
PMID??: PMID:17055429
MYC stimulate P53 and ARF
em_re1572( EMT Senescence ):
PMID:17533374
HIF-1 and NF-kappaB upregulates CXCR1 and CXCR2 expression
Chemokine receptor CXCR2 is transactivated by p53
References
ce_re34:( Cell Cycle DNA Repair ) PMID:19788416
ce_re226( Cell Cycle DNA Repair ):
BRCA1 up-regulates transcription of GADD45 in p53 independed manner:
PMID:10367887, PMID:10962562
PMID:19004803, PMID:12496474
p53 enhances transcription of GADD45:
PMID:9892649, PMID:10779360
p53 regulated global genomic NER at the level of DNA damage recognition involving GADD45, XPC, DDB2:
PMID:12771027, PMID:9346961
ce_re228( Cell Cycle DNA Repair ):
BRCA1 enhances transcription of DDB2 in p53 independent manner
PMID:19004803, PMID:12496474, PMID:12170778
p53 enhances transcription of DDB2:
ce_re231( Cell Cycle DNA Repair ):
BRCA1 upregulates transcription of XPC in p53 independed manner:
p53 enhances transcription of XPC:
ce_re344:( Cell Cycle DNA Repair ) CHECKPOINT is p53_dependent_G1S_checkpoint
Maps_Modules
HMC:RESISTING_CELL_DEATH
HMC:DEREGULATING_CELLULAR_ENERGETICS
Regulated Cell Death / ANTIOXIDANT_RESPONSE
Regulated Cell Death / APOPTOSIS
Regulated Cell Death / STARVATION_AUTOPHAGY
Regulated Cell Death / DEATH_RECEPTOR_PATHWAYS
Regulated Cell Death / DNA_DAMAGE_RESPONSE
Regulated Cell Death / MOMP_REGULATION
Regulated Cell Death / RCD_GENES
Regulated Cell Death / PENTOSE_PHOSPHATE_PATHWAY
References
rc_re1406( Regulated Cell Death ):
PMID:18845789
unphosphorylated TP53 from coIP experiments with okadaic acid (PKC inhibitor) or ceramide C2 (potent inductor of PP1/2A
PMID:26801188
rc_re1668:( Regulated Cell Death ) PMID:21887410
Maps_Modules
HMC:RESISTING_CELL_DEATH
HMC:DEREGULATING_CELLULAR_ENERGETICS
Regulated Cell Death / ANTIOXIDANT_RESPONSE
Regulated Cell Death / APOPTOSIS
Regulated Cell Death / STARVATION_AUTOPHAGY
Regulated Cell Death / DEATH_RECEPTOR_PATHWAYS
Regulated Cell Death / DNA_DAMAGE_RESPONSE
Regulated Cell Death / MOMP_REGULATION
Regulated Cell Death / RCD_GENES
Regulated Cell Death / PENTOSE_PHOSPHATE_PATHWAY
References
rc_re1128:( Regulated Cell Death ) PMID:23030059
rc_re98( Regulated Cell Death ):
PMID:18056423
p53 mediated upregulation of IGFBP1
in mouse liver
PMID:9707622
in HepG2, by HIF1
PMID:10102273
in 293T, by FOXO3, EMSA
rc_re106( Regulated Cell Death ):
PMID:18208354
TP53 downregulates the activity of the MCL1 gene promoter in Hela and HEK293
mainly through an unkown mechanism. Critical importance of the -41 to +16 region that correspond to TATA-BP and other basal transcription factors binding
also through down regulation of Sp1
PMID:19808698
in MV4-11 cells, a human biphenotypic B myelomonocytic leukemia that displays FLT3-ITD mutation (constitutive FLT3 signalling), STAT5* siRNA prevents MCL1 expression
PMID:11160159
in large granular lymphocyte high STAT3 activity correlates with MCL1 expression, AG-490 JAK inhibitors induce apoptosis and decreases MCL1 expression.
in NIH3T3, upon v-src, STAT3 dependent expression of MCL1
rc_re108:( Regulated Cell Death ) PMID:17409411
rc_re115( Regulated Cell Death ):
PMID:7566179
in EB1 colon carninoma cells expressing p53 under the control of an inducible promoter
in Saos-2 huamn osteosarcoma cells expressing a temperature sensitive p53
PMID:17409411
in mouse spleen and thymus upon irradiation
rc_re118( Regulated Cell Death ):
PMID:18692468
PMID:9926927
rc_re119( Regulated Cell Death ):
PMID:12203114
rc_re124:( Regulated Cell Death ) PMID:19203586
rc_re126( Regulated Cell Death ):
PMID:14699081
in Saos-2, direct transactivation of NOXA by HIF1A during hypoxia, role of NOXA in hypoxia-induced cell death
PMID:16888645
in SH-EP, in NB15 neuroblastoma cell lines expressing a FOXO3-ER fusion, upon 4OHT. PMAIP knock down protects from apoptosis
PMID:12676992
in MEF by CTBP1 and CTBP2 (RT-PCR, double knocked out)
PMID:14684737
in NIH3T3, by E2F1
rc_re127( Regulated Cell Death ):
PMID:11463391
by p53
PMID:11463392
PMID:14634023
in Saos-2, by p73
in NIH3T3 and in Saos-2, by E2F1
rc_re130( Regulated Cell Death ):
PMID:12402042
in mouse splenic red pulp and colonic epithelium, upon irradiation
in human, the p53 binding element is conserved
PMID:15024076
in HT29 and CHO, HIF1-dependent hypoxia-induced repression of BID expression
in SW480 upon hypoxia, interaction between HIF1 and BID promoter, by EMSA
PMID:15240700
in mouse T cells, by E2F1
rc_re131( Regulated Cell Death ):
PMID:19211844
FOXO3 mediated inhibition
PMID:11714700
TP53 mediated inhibition
PMID:11965534
rc_re133:( Regulated Cell Death ) PMID:17000778
rc_re134( Regulated Cell Death ):
PMID:7834749
PMID:15613549
in HEK 293, by NFkB, upon expression of LMP1 protein (from EBV). More precisely, p65/p50 dimer inhibits BAX promoter activity whereas p50/p50 dimer is actually an transcriptional activator or BAX. However p65 has to be inhibited to see p50/p50 mediated activation of BAX
in MEF double knocked out by CTBP1 and CTBP2 (RT-PCR)
rc_re136( Regulated Cell Death ):
PMID:8242752
by TP53
rc_re137:( Regulated Cell Death ) PMID:16728594
rc_re139( Regulated Cell Death ):
PMID:11389439
PMID:11591730
PMID:11559530
rc_re140:( Regulated Cell Death ) PMID:16839880
rc_re141( Regulated Cell Death ):
PMID:17554199
PMID:17656095
PMID:17540599
PMID:17554337
PMID:19696787
in TIG3 TERT/??B-RAF:ER, by ELK1 (siRNA ELK1 and MIR34A PCR; ChIP)
in HEK293 by ELK1, gene reporter
rc_re142( Regulated Cell Death ):
PMID:14985507
mouse homolog siah-1b is a direct target of p53
PMID:12077306
sequence analysis predicts SIAH1 as a p53 target gene
PMID:12438652
in human colorectal carcinoma-derived cell lines with a somatic knock-out of p53 (p53 +/+, p53 +/???, and p53 ???/???), SIAH1 expression correlates with that of p53
rc_re146( Regulated Cell Death ):
PMID:18328430
MIR17HG transactivation by E2F1
PMID:15944709
MIR17-92 cluster transactivation by MYC
PMID:19696742
MIR17HG transactivation repressed by TP53. Proposed mechanism: TP53- and TBP- binding sites overlaps.
in human colorectal carcinoma HCT116 (TP53 competent cells), MIR17HG repression upon hypoxia and TP53 stabilization.
in human colorectal carcinoma cells HCT116 and LOVO, this effect is blocked by siRNA against TP53
in HCT116 and LOVO, siRNA against MYC represses MIR17-92 expression
rc_re174( Regulated Cell Death ):
PMID:7493931
in HepG2 by HIF1 (EMSA, reporter plasmids)
PMID:9525945
in chinese hamster ovary cells by HIF1
PMID:15059920
in Saos2, in human embryonal rhabdomyosarcoma derived RD (ATCC no. CCL-136), in murine skeletal muscle-derived C2C12 myoblasts (ATCC no. CRL-1772), by TP53 (luciferase reporter)
rc_re215( Regulated Cell Death ):
PMID:11704864
in LNCaP human prostate cancer cell line
PMID:11313951
transrepression by p53
rc_re381:( Regulated Cell Death ) PMID:15105421
rc_re784:( Regulated Cell Death ) PMID:10716435
rc_re1127( Regulated Cell Death ):
PMID:19590512
Siva1 and mdm2
PMID:15989956
HUWE1
PMID:19960022
effect of SIRT1 K382-deacetylation
rc_re1198( Regulated Cell Death ):
PMID:20308559
in Hela cells
in HCT116 wt, but not in p53-deficient conterpart, etoposide induces the expression of PANK1 and MIR107, + luciferase reporter and ChIP assays
rc_re1222:( Regulated Cell Death ) PMID:20378837
rc_re1229( Regulated Cell Death ):
in Saos2, in human embryonal rhabdomyosarcoma derived RD (ATCC no. CCL-136), in murine skeletal muscle-derived C2C12 myoblasts (ATCC no. CRL-1772), by TP53 (luciferase reporter) upon transfection, but not by mutant TP53
in vitro binding of in vitro translated TP53 to the promoter
rc_re1235( Regulated Cell Death ):
PMID:16839881
PMID:23030059
rc_re1403( Regulated Cell Death ):
PMID:15073321
PMID:10973264
References
s_akt2_re70( Survival ):
PMID:10721693
PMID:19459846
References
s_akt2_re77( Survival ):
PMID:10721693
PMID:19459846
→ p53*|pho|ace|active@Nucleus
+ PARP1|PolyADPribose_unk|pho@Nucleus → ce_s2572
→ degraded
→ p53*|pho@Nucleus
+ MDM2|S186_pho@Nucleus → MDM2|S186_pho:p53*@Nucleus
→ MDM2|S186_pho:p53*@Cytosol
→ degraded
+ MDM2|S186_pho:p53*@Nucleus → MDM2|S186_pho:SNAI2:p53*@Nucleus
→ degraded
+ NICD*@Nucleus → NICD*:p53*@Nucleus
→ degraded
+ p53*@Mitochondria → BCL2-XL*:p53*@Mitochondria
→ p53*@Mitochondria
+ BCL2@Mitochondria → BCL2:p53*@Mitochondria
+ BAX@Cytosol → BAX:p53*@Cytosol
→ Apoptosis@Cytosol
+ BAK1@Mitochondria → BAK1:p53*@Mitochondria
→ Apoptosis@Cytosol
→ p53*@Nucleus
→ p53*@Nucleus
→ p53*|ubi@Cytosol
→ Cell survival@Cytosol
→ p53*@Nucleus
→ p53*|S15_pho|active@Nucleus
+ p53*|S15_unk@Cytosol → BCL2:p53*@Mitochondrial inner membrane
+ p53*|S15_unk@Cytosol → BCL2-XL*:p53*@Mitochondrial inner membrane
→ p53*@Nucleus
→ degraded
→ p53*@Cytosol
→ rc_s7704
→ p53*|ubi@Nucleus
→ p53*|ubi@Cytoplasm
→ p53*|ubi|ubi@Nucleus
→ p53*|pho@Nucleus
→ gGADD45*@Nucleus
→ gp21CIP1*@Nucleus
→ gPERP@Nucleus
→ gMDM2@Nucleus
→ gPMAIP1@Nucleus
→ gDDB2@Nucleus
→ p53*@Nucleus
→ Apoptosis@Cytoplasm
→ Apoptosis@Nucleus
→ p53-target genes@Nucleus
+ p53*@Nucleus + HIPK2@Nucleus → AXIN*:HIPK2@Nucleus
→ AXIN*:HIPK2:p53*|S46_pho@Nucleus
→ rGADD45*@Nucleus
→ rDDB2@Nucleus
→ rXPC@Nucleus
→ rCIP/KIP*@Nucleus
→ ce_s2495
→ r14-3-3*@Nucleus
→ arMIR200C@Nucleus
→ rp21CIP1*@Nucleus
→ arMIR203A@Nucleus
→ rPTEN@Nucleus
→ SNAI2@Nucleus
→ rBIM*@Nucleus
→ rCXCR2@Nucleus
→ rULBP2@TUMOR_CELL_AS_INDUCTOR
→ rUDLP1@TUMOR_CELL_AS_INDUCTOR
→ arMIR34A@TUMOR_CELL_AS_INDUCTOR
→ arMIR34C@TUMOR_CELL_AS_INDUCTOR
→ rPTP4A3@Nucleus
→ rPKA_R*@Nucleus
→ rMCL1@Nucleus
→ rPTEN@Nucleus
→ rTSC2@Nucleus
→ rIGFBP3@Nucleus
→ rSESN1@Nucleus
→ rSESN2@Nucleus
→ rpre-mRNA~PANK1*@Nucleus
→ rGLS2@Nucleus
→ rSLC2A4@Nucleus
→ rDRAM1@Nucleus
→ rPHLDA3@Nucleus
→ rPMAIP1@Nucleus
→ rBBC3@Nucleus
→ rPYCARD@Nucleus
→ rBID@Nucleus
→ rBIRC5@Nucleus
→ rBAD@Nucleus
→ rBAX@Nucleus
→ rp21CIP1*@Nucleus
→ rSCO2@Nucleus
→ rAPAF1@Nucleus
→ rTIGAR*@Nucleus
→ rLRDD@Nucleus
→ arMIR34A@Cytosol
→ rSIAH1@Nucleus
→ arMIR17-92*@Nucleus
→ rSLC2A1@Nucleus
→ rBCL2@Nucleus
→ rSLC7A11@Nucleus
→ rSIVA1@Nucleus
→ rRRM2B@Nucleus
→ rIGFBP1@Nucleus
→ rMDM2@Nucleus
→ arMIR34A@Nucleus
→ arMIR34B@Nucleus
→ arMIR34C@Nucleus
→ rTERT@Nucleus