PMADS

Id:	acc1839
Group:	2sens
Protein:	p53
Gene Symbol:	TP53
Protein Id:	P04637
Protein Name:	P53_HUMAN
PTM:	acetylation
Site:	Lys373
Site Sequence:	AHSSHLKSKKGQSTSRHKKLM
Disease Category:	Cancer
Disease:	Breast Cancer
Disease Subtype:	ER+/PR+
Disease Cellline:	MCF7
Disease Info:
Drug:	MS-275
Drug Info:	"MS-275 (Entinostat) is a selective class I histone deacetylase (HDAC) inhibitor that targets HDAC1, HDAC2, and HDAC3, exhibiting potent anti-proliferative activity and inducing apoptosis in various cancer cells, and has entered clinical trials for tumor therapy."
Effect:	modulate
Effect Info:	"Treatment with MS-275 reduces the interaction between p53 and p21, increases the high acetylation level at the C-terminus of p53, and interferes with the cooperative regulation of cell invasion and death by p53 and p21."
Note:	site unclear
Score:	4.0
Pubmed(PMID):	36257192
Sentence Index:	36257192_2-3
Sentence:	"As p53 binds to p21 via its C-terminal domain, which contains acetylable lysine residues, we investigated whether the C-terminal acetylation of p53 influences the p53/p21 interaction. Indeed, the p53/p21 interaction was reduced when various types of cells (HCT116 colon cancer, A549 lung cancer, and MCF7 breast cancer cells) were treated with MS-275, an inhibitor of SIRT1 (a p53 deacetylase), or with SIRT1-targeting small interfering RNAs."

Sequence & Structure:

MEEPQSDPSVEPPLSQETFSDLWKLLPENNVLSPLPSQAMDDLMLSPDDIEQWFTEDPGPDEAPRMPEAAPPVAPAPAAPTPAAPAPAPSWPLSSSVPSQKTYQGSYGFRLGFLHSGTAKSVTCTYSPALNKMFCQLAKTCPVQLWVDSTPPPGTRVRAMAIYKQSQHMTEVVRRCPHHERCSDSDGLAPPQHLIRVEGNLRVEYLDDRNTFRHSVVVPYEPPEVGSDCTTIHYNYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGEPHHELPPGSTKRALPNNTSSSPQPKKKPLDGEYFTLQIRGRERFEMFRELNEALELKDAQAGKEPGGSRAHSSHLKSKKGQSTSRHKKLMFKTEGPDSD

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target	Drug name	MOA	Phase	Status	Disease	Source
TP53	EPRENETAPOPT	Cellular tumor antigen p53 stabiliser	3	Completed	myelodysplastic syndrome	ClinicalTrials
TP53	IDASANUTLIN	Tumour suppressor p53/oncoprotein Mdm2 inhibitor	3	Terminated	acute myeloid leukemia	ClinicalTrials
TP53	CENERSEN SODIUM	p53 mRNA antisense inhibitor	2	Terminated	chronic lymphocytic leukemia	ClinicalTrials
TP53	CENERSEN	p53 mRNA antisense inhibitor	2	Completed	acute myeloid leukemia	ClinicalTrials
TP53	CENERSEN	p53 mRNA antisense inhibitor	2	Withdrawn	acute myeloid leukemia	ClinicalTrials
TP53	NAVTEMADLIN	Tumour suppressor p53/oncoprotein Mdm2 inhibitor	2	Recruiting	essential thrombocythemia	ClinicalTrials
TP53	SIREMADLIN	Tumour suppressor p53/oncoprotein Mdm2 inhibitor	2	Recruiting	neoplasm	ClinicalTrials
TP53	IDASANUTLIN	Tumour suppressor p53/oncoprotein Mdm2 inhibitor	2	Recruiting	neoplasm	ClinicalTrials
TP53	NAVTEMADLIN	Tumour suppressor p53/oncoprotein Mdm2 inhibitor	2	Terminated	small cell lung carcinoma	ClinicalTrials
TP53	NAVTEMADLIN	Tumour suppressor p53/oncoprotein Mdm2 inhibitor	2	Active, not recruiting	polycythemia vera	ClinicalTrials
TP53	NAVTEMADLIN	Tumour suppressor p53/oncoprotein Mdm2 inhibitor	2	Recruiting	polycythemia vera	ClinicalTrials
TP53	NAVTEMADLIN	Tumour suppressor p53/oncoprotein Mdm2 inhibitor	2	Recruiting	primary myelofibrosis	ClinicalTrials
TP53	IDASANUTLIN	Tumour suppressor p53/oncoprotein Mdm2 inhibitor	2	Terminated	polycythemia vera	ClinicalTrials
TP53	CONTUSUGENE LADENOVEC	Cellular tumor antigen p53 exogenous gene	2	Unknown status	non-small cell lung carcinoma	ClinicalTrials
TP53	APG115	Tumour suppressor p53/oncoprotein Mdm2 inhibitor	2	Recruiting	lymphoid leukemia	ClinicalTrials
TP53	CONTUSUGENE LADENOVEC	Cellular tumor antigen p53 exogenous gene	2	Terminated	head and neck malignant neoplasia	ClinicalTrials
TP53	CONTUSUGENE LADENOVEC	Cellular tumor antigen p53 exogenous gene	2	Unknown status	head and neck malignant neoplasia	ClinicalTrials ClinicalTrials
TP53	EPRENETAPOPT	Cellular tumor antigen p53 stabiliser	2	Withdrawn	Mantle cell lymphoma	ClinicalTrials
TP53	TEPRASIRAN	p53 mRNA RNAi inhibitor	2	Completed	Acute kidney injury	ClinicalTrials
TP53	EPRENETAPOPT	Cellular tumor antigen p53 stabiliser	2	Completed	ovarian cancer	ClinicalTrials
TP53	CONTUSUGENE LADENOVEC	Cellular tumor antigen p53 exogenous gene	2	Completed	breast cancer	ClinicalTrials
TP53	NAVTEMADLIN	Tumour suppressor p53/oncoprotein Mdm2 inhibitor	2	Recruiting	endometrial cancer	ClinicalTrials
TP53	CENERSEN	p53 mRNA antisense inhibitor	1	Terminated	myelodysplastic syndrome	ClinicalTrials
TP53	NAVTEMADLIN	Tumour suppressor p53/oncoprotein Mdm2 inhibitor	1	Active, not recruiting	acute myeloid leukemia	ClinicalTrials ClinicalTrials
TP53	NAVTEMADLIN	Tumour suppressor p53/oncoprotein Mdm2 inhibitor	1	Completed	acute myeloid leukemia	ClinicalTrials

Note: Only show clinically investigational or approved drugs with protein targets.

Protein Tractability:

source: Open Targets

Small molecule

Antibody

PROTAC

Other modalities

Approved Drug

Advanced Clinical

Phase 1 Clinical

Structure with Ligand

High-Quality Ligand

High-Quality Pocket

Med-Quality Pocket

Druggable Family

Approved Drug

Advanced Clinical

Phase 1 Clinical

UniProt loc high conf

GO CC high conf

UniProt loc med conf

UniProt SigP or TMHMM

GO CC med conf

Human Protein Atlas loc

Approved Drug

Advanced Clinical

Phase 1 Clinical

Literature

UniProt Ubiquitination

Database Ubiquitination

Half-life Data

Small Molecule Binder

Approved Drug

Advanced Clinical

Phase 1 Clinical

PTM Intensity:

source: CPTAC

No intensity data of this site,
show all other sites!

TP53-Lys305
Cancer	Intensity
BRCA	-1.121
COAD
HGSC
ccRCC
GBM
HNSC
LUAD
LUSC	0.799
non_ccRCC
PDAC
UCEC	0.322

TP53-Lys357
Cancer	Intensity
BRCA	0.707
COAD
HGSC
ccRCC
GBM
HNSC
LUAD
LUSC	-0.707
non_ccRCC
PDAC
UCEC

TP53BP1-Lys1365
Cancer	Intensity
BRCA	-0.326
COAD
HGSC
ccRCC
GBM	1.485
HNSC
LUAD
LUSC	-0.671
non_ccRCC
PDAC
UCEC	-0.488

TP53BP1-Lys1631
Cancer	Intensity
BRCA	-1.355
COAD
HGSC
ccRCC
GBM	0.775
HNSC
LUAD	0.725
LUSC	0.644
non_ccRCC
PDAC
UCEC	-0.79

TP53BP1-Lys1672
Cancer	Intensity
BRCA	-1.476
COAD
HGSC
ccRCC
GBM	0.981
HNSC
LUAD	0.475
LUSC	-0.553
non_ccRCC
PDAC
UCEC	0.573

TP53BP1-Lys1674
Cancer	Intensity
BRCA	0.052
COAD
HGSC
ccRCC
GBM
HNSC
LUAD	-1.025
LUSC
non_ccRCC
PDAC
UCEC	0.973

TP53BP1-Lys222
Cancer	Intensity
BRCA	0.901
COAD
HGSC
ccRCC
GBM
HNSC
LUAD	-1.128
LUSC	0.781
non_ccRCC
PDAC
UCEC	-0.554

TP53BP1-Lys255
Cancer	Intensity
BRCA	0.707
COAD
HGSC
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	-0.707

TP53BP1-Lys610
Cancer	Intensity
BRCA	0.707
COAD
HGSC
ccRCC
GBM
HNSC
LUAD
LUSC	-0.707
non_ccRCC
PDAC
UCEC

TP53BP1-Lys878
Cancer	Intensity
BRCA	-1.108
COAD
HGSC
ccRCC
GBM
HNSC
LUAD
LUSC	0.837
non_ccRCC
PDAC
UCEC	0.271

TP53I3-Lys176
Cancer	Intensity
BRCA	-1.515
COAD
HGSC
ccRCC
GBM	0.409
HNSC
LUAD	-0.378
LUSC	1.124
non_ccRCC
PDAC
UCEC	0.361

TP53I3-Lys177
Cancer	Intensity
BRCA	0.707
COAD
HGSC
ccRCC
GBM	-0.707
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

TP53I3-Lys183
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM
HNSC
LUAD	0.901
LUSC	0.175
non_ccRCC
PDAC
UCEC	-1.076

TP53I3-Lys193
Cancer	Intensity
BRCA	0.455
COAD
HGSC
ccRCC
GBM	-0.602
HNSC
LUAD	-0.304
LUSC	-1.046
non_ccRCC
PDAC
UCEC	1.498

TP53I3-Lys203
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM
HNSC
LUAD	-0.771
LUSC	-0.359
non_ccRCC
PDAC
UCEC	1.13

TP53I3-Lys321
Cancer	Intensity
BRCA	-0.81
COAD
HGSC
ccRCC
GBM	-1.262
HNSC
LUAD	0.289
LUSC	1.09
non_ccRCC
PDAC
UCEC	0.692

PTM-Disease Association:

source: PTMD

Residue	Position	State	Disease	Class	PMID
K	373	D	Breast cancer	Acetylation	37156774
K	373	D	Hepatocellular carcinoma	Acetylation	37963859
K	373	U	Triple-negative breast cancer	Acetylation	29334665
K	373	U	Lung cancer	Neddylation	37668436

State Note: Based on the distinct PTM states in diseases, PTMD classified all disease-associated PTMs into six classes, including whether the up-regulation (U) or down-regulation (D) of PTM levels, the absence (A) or presence (P) of PTMs, and the creation (C) or disruption (N) of PTM sites are associated with diseases.

PTM-Drug Perturbation Response:

source: DecryptM

No data.

Function score:

source: funscoR

No data.

Cross Links:

CTD
DMRdb