Biomarker: p53

Histology type: endometrial carcinoma

Country: Greece

Region: Athens

Study type: retrospective study

Followed up time :

Subgroup 1 name : Positive

Subgroup 1 number: 11

Subgroup 2 name: Negative

Subgroup 2 number: 38

Conclusion: P53 immunoexpression helps both in accurate diagnosis and proper therapeutic approach of the various endometrial carcinomas.

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : positive (>10% of the nuclei of neoplastic cell population)

Expression elevation: Positive immuno reaction was graded semi quantitatively: cases with positive p53 immunoreaction in>10% of the nuclei of neoplastic cell population

Statictics: Mean ;Range

Cohort age: 72.5;39-75

Funtion Uniprot: Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775, PubMed:15340061, PubMed:17317671, PubMed:17349958, PubMed:19556538, PubMed:20673990, PubMed:20959462, PubMed:22726440, PubMed:24051492, PubMed:9840937, PubMed:24652652). 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 (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775, PubMed:15340061, PubMed:17317671, PubMed:17349958, PubMed:19556538, PubMed:20673990, PubMed:20959462, PubMed:22726440, PubMed:24051492, PubMed:9840937, PubMed:24652652). 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. Its pro-apoptotic activity is activated via its interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 (PubMed:12524540). However, this activity is inhibited when the interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 is displaced by PPP1R13L/iASPP (PubMed:12524540). 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 seems to have an 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 stopping cell 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).

UniProt ID: P04637

UniProt Link: https://www.uniprot.org/uniprotkb/P04637/entry

Biological function from UniProt: Apoptosis, Biological rhythms, Cell cycle, Host-virus interaction, Necrosis, Transcription, Transcription regulation

Molecular function from UniProt:

Tissue specificity from UniProt: Ubiquitous. Isoforms are expressed in a wide range of normal tissues but in a tissue-dependent manner. Isoform 2 is expressed in most normal tissues but is not detected in brain, lung, prostate, muscle, fetal brain, spinal cord and fetal liver. Isoform 3 is expressed in most normal tissues but is not detected in lung, spleen, testis, fetal brain, spinal cord and fetal liver. Isoform 7 is expressed in most normal tissues but is not detected in prostate, uterus, skeletal muscle and breast. Isoform 8 is detected only in colon, bone marrow, testis, fetal brain and intestine. Isoform 9 is expressed in most normal tissues but is not detected in brain, heart, lung, fetal liver, salivary gland, breast or intestine.

Subcellular UniProt: #Cytoplasm #Cytoskeleton #Endoplasmic reticulum #Mitochondrion #Nucleus

Alternative name from UniProt:

Caution: Interaction with BANP was reported to enhance phosphorylation on Ser-15 upon ultraviolet irradiation (PubMed:15701641). However, the publication has been retracted due to image duplication and manipulation. Interaction with BANP has been confirmed in mouse studies (By similarity). Phosphorylation at Ser-15 has been confirmed by other studies (PubMed:10570149, PubMed:11554766, PubMed:16219768, PubMed:15866171, PubMed:17317671, PubMed:17954561, PubMed:20959462, PubMed:25772236). Its nuclear and cytoplasmic localization has been confirmed by other studies (PubMed:15340061, PubMed:17170702, PubMed:19011621, PubMed:21597459, PubMed:22726440, PubMed:17591690, PubMed:18206965).

Recommended name: Cellular tumor antigen p53

Gene name from HGNC: TP53 (LFS1, p53)

HPA class: Cancer-related genes Disease related genes Human disease related genes Plasma proteins Potential drug targets Transcription factors Transporters

AlphaFold DB: P04637

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/P04637

Induction: Up-regulated in response to DNA damage. Isoform 2 is not induced in tumor cells in response to stress.

HPA link: https://www.proteinatlas.org/ENSG00000141510-TP53

Tissue specificity RNA from HPA: Low tissue specificity

Tissue expression from HPA: Fractions of cells showed weak nuclear and/or cytoplasmic expression.

Single cell type specificity T-cells - Adaptive immune response (mainly)

Immune cell specificity: Low immune cell specificity

Subcellular summary HPA Located in Nucleoplasm, Mitochondria, Cytosol (Single cell variability, CCD Protein)

Cancer prognostic summary HPA Prognostic marker in endometrial cancer (favorable) and prostate cancer (unfavorable)

Pathology link: https://www.proteinatlas.org/ENSG00000141510-TP53/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000141510-TP53/pathology/endometrial+cancer

Phenotype ID: | 133239| 151623| 275355| 211980| 260500| 202300|614740|618165

Disease: No disease ID | Esophageal cancer (ESCR)|Li-Fraumeni syndrome (LFS)|Squamous cell carcinoma of the head and neck (HNSCC)|Lung cancer (LNCR)|Papilloma of choroid plexus (CPP)|Adrenocortical carcinoma (ADCC)|Basal cell carcinoma 7 (BCC7)|Bone marrow failure syndrome 5 (BMFS5)

Note1: TP53 is found in increased amounts in a wide variety of transformed cells. TP53 is frequently mutated or inactivated in about 60% of cancers. TP53 defects are found in Barrett metaplasia a condition in which the normally stratified squamous epithelium of the lower esophagus is replaced by a metaplastic columnar epithelium. The condition develops as a complication in approximately 10% of patients with chronic gastroesophageal reflux disease and predisposes to the development of esophageal adenocarcinoma | The disease is caused by variants affecting the gene represented in this entry| The disease is caused by variants affecting the gene represented in this entry|The gene represented in this entry is involved in disease pathogenesis|The disease is caused by variants affecting the gene represented in this entry|The disease is caused by variants affecting the gene represented in this entry|The disease is caused by variants affecting the gene represented in this entry|Disease susceptibility is associated with variants affecting the gene represented in this entry|The disease is caused by variants affecting the gene represented in this entry

OMIM: 191170

OMIM link1: | https://www.omim.org/entry/133239|https://www.omim.org/entry/151623| https://www.omim.org/entry/275355| https://www.omim.org/entry/211980| https://www.omim.org/entry/260500| https://www.omim.org/entry/202300| https://www.omim.org/entry/614740|https://www.omim.org/entry/618165

OMIM link2: https://www.omim.org/entry/191170

HGNC ID: HGNC:11998

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11998