Target General Infomation
Target ID
T82051
Former ID
TTDI02325
Target Name
mRNA of p53
Gene Name
TP53
Synonyms
Antigen NYCO13 (mRNA); Cellular tumor antigen p53 (mRNA); Phosphoprotein p53 (mRNA); TP53 (mRNA); Tumor suppressor p53 (mRNA); TP53
Target Type
Clinical Trial
Disease Acute myeloid leukemia [ICD9: 205; ICD10: C92.0]
Hearing disorder [ICD10: H90.5]
Function
Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA- Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seem to have to effect on cell-cycle regulation. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stoppingcell cycle progression. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis. Regulates the circadian clock by repressing CLOCK-ARNTL/BMAL1- mediated transcriptional activation of PER2 (PubMed:24051492). {ECO:0000269|PubMed:11025664, ECO:0000269|PubMed:12810724, ECO:0000269|PubMed:15186775, ECO:0000269|PubMed:15340061, ECO:0000269|PubMed:17317671, ECO:0000269|PubMed:17349958, ECO:0000269|PubMed:19556538, ECO:0000269|PubMed:20673990, ECO:0000269|PubMed:20959462, ECO:0000269|PubMed:22726440, ECO:0000269|PubMed:24051492, ECO:0000269|PubMed:9840937}.
BioChemical Class
Target of siRNA drug
UniProt ID
Sequence
MEEPQSDPSVEPPLSQETFSDLWKLLPENNVLSPLPSQAMDDLMLSPDDIEQWFTEDPGP
DEAPRMPEAAPPVAPAPAAPTPAAPAPAPSWPLSSSVPSQKTYQGSYGFRLGFLHSGTAK
SVTCTYSPALNKMFCQLAKTCPVQLWVDSTPPPGTRVRAMAIYKQSQHMTEVVRRCPHHE
RCSDSDGLAPPQHLIRVEGNLRVEYLDDRNTFRHSVVVPYEPPEVGSDCTTIHYNYMCNS
SCMGGMNRRPILTIITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGEPHHELP
PGSTKRALPNNTSSSPQPKKKPLDGEYFTLQIRGRERFEMFRELNEALELKDAQAGKEPG
GSRAHSSHLKSKKGQSTSRHKKLMFKTEGPDSD
Drugs and Mode of Action
Drug(s) Cenersen Drug Info Phase 2 Acute myeloid leukemia [531537], [543025]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway MAPK signaling pathway
Sphingolipid signaling pathway
Cell cycle
p53 signaling pathway
PI3K-Akt signaling pathway
Apoptosis
Wnt signaling pathway
Neurotrophin signaling pathway
Thyroid hormone signaling pathway
Amyotrophic lateral sclerosis (ALS)
Huntington&#039
s disease
Hepatitis C
Hepatitis B
Measles
HTLV-I infection
Herpes simplex infection
Epstein-Barr virus infection
Pathways in cancer
Transcriptional misregulation in cancer
Viral carcinogenesis
Proteoglycans in cancer
MicroRNAs in cancer
Colorectal cancer
Pancreatic cancer
Endometrial cancer
Glioma
Prostate cancer
Thyroid cancer
Basal cell carcinoma
Melanoma
Bladder cancer
Chronic myeloid leukemia
Small cell lung cancer
Non-small cell lung cancer
Central carbon metabolism in cancer
NetPath Pathway FSH Signaling Pathway
PANTHER Pathway Apoptosis signaling pathway
Huntington disease
Wnt signaling pathway
p53 pathway
P53 pathway feedback loops 1
p53 pathway by glucose deprivation
p53 pathway feedback loops 2
Pathway Interaction Database Signaling events mediated by HDAC Class III
Validated targets of C-MYC transcriptional activation
LKB1 signaling events
Glucocorticoid receptor regulatory network
Direct p53 effectors
p75(NTR)-mediated signaling
AP-1 transcription factor network
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha
Signaling mediated by p38-alpha and p38-beta
Aurora A signaling
BARD1 signaling events
p53 pathway
PLK3 signaling events
Reactome Activation of NOXA and translocation to mitochondria
Activation of PUMA and translocation to mitochondria
Pre-NOTCH Transcription and Translation
Oxidative Stress Induced Senescence
Formation of Senescence-Associated Heterochromatin Foci (SAHF)
Oncogene Induced Senescence
DNA Damage/Telomere Stress Induced Senescence
Autodegradation of the E3 ubiquitin ligase COP1
TP53 Regulates Metabolic Genes
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
Stabilization of p53
Factors involved in megakaryocyte development and platelet production
WikiPathways DNA Damage Response (only ATM dependent)
DNA Damage Response
ErbB Signaling Pathway
Senescence and Autophagy in Cancer
G1 to S cell cycle control
Sandbox Pathway
Wnt Signaling Pathway and Pluripotency
TGF beta Signaling Pathway
Copper homeostasis
Bladder Cancer
Mammary gland development pathway - Involution (Stage 4 of 4)
Pre-NOTCH Expression and Processing
Apoptosis
ATM Signaling Pathway
Amyotrophic lateral sclerosis (ALS)
Retinoblastoma (RB) in Cancer
Spinal Cord Injury
Integrated Pancreatic Cancer Pathway
Oncostatin M Signaling Pathway
Gastric cancer network 2
Prostate Cancer
Signaling Pathways in Glioblastoma
Metastatic brain tumor
Alzheimers Disease
Integrated Breast Cancer Pathway
Integrated Cancer pathway
Intrinsic Pathway for Apoptosis
Factors involved in megakaryocyte development and platelet production
Cell Cycle
Cell Cycle Checkpoints
Apoptosis Modulation and Signaling
Folate Metabolism
TP53 Network
Fluoropyrimidine Activity
miRNAs involved in DNA damage response
miRNA Regulation of DNA Damage Response
AMPK Signaling
References
Ref 531537Phase 2 randomized study of p53 antisense oligonucleotide (cenersen) plus idarubicin with or without cytarabine in refractory and relapsed acute myeloid leukemia. Cancer. 2012 Jan 15;118(2):418-27.
Ref 543025(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8270).
Ref 531537Phase 2 randomized study of p53 antisense oligonucleotide (cenersen) plus idarubicin with or without cytarabine in refractory and relapsed acute myeloid leukemia. Cancer. 2012 Jan 15;118(2):418-27.

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