Protein: Cellular tumor antigen p53 (Antigen NY-CO-13) (Phosphoprotein p53) (Tumor suppressor p53) (P04637)
Organism: Homo sapiens (Human)
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. Its pro-apoptotic activity is activated via its interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2. However, this activity is inhibited when the interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 is displaced by PPP1R13L/iASPP. 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-BMAL1-mediated transcriptional activation of PER2.
Subcellular location: Cytoplasm {ECO:0000269|PubMed:15340061, ECO:0000269|PubMed:17170702, ECO:0000269|PubMed:19011621, ECO:0000269|PubMed:19033443, ECO:0000269|PubMed:21597459, ECO:0000269|PubMed:22726440, ECO:0000269|PubMed:24625977, ECO:0000269|PubMed:26634371}. Nucleus {ECO:0000269|PubMed:15340061, ECO:0000269|PubMed:17170702, ECO:0000269|PubMed:17591690, ECO:0000269|PubMed:18206965, ECO:0000269|PubMed:19011621, ECO:0000269|PubMed:21597459, ECO:0000269|PubMed:24625977, ECO:0000269|PubMed:26634371}. Nucleus, PML body {ECO:0000269|PubMed:11025664, ECO:0000269|PubMed:12810724, ECO:0000269|PubMed:36108750}. Endoplasmic reticulum {ECO:0000269|PubMed:17170702}. Mitochondrion matrix {ECO:0000269|PubMed:22726440, ECO:0000269|PubMed:25168243, ECO:0000269|PubMed:27323408}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:28842590}. Note=Recruited into PML bodies together with CHEK2 (PubMed:12810724). Translocates to mitochondria upon oxidative stress (PubMed:22726440). Translocates to mitochondria in response to mitomycin C treatment (PubMed:27323408). Competitive inhibition of TP53 interaction with HSPA9/MOT-2 by UBXN2A results in increased protein abundance and subsequent translocation of TP53 to the nucleus (PubMed:24625977). {ECO:0000269|PubMed:12810724, ECO:0000269|PubMed:22726440, ECO:0000269|PubMed:24625977, ECO:0000269|PubMed:27323408}.; SUBCELLULAR LOCATION: [Isoform 1]: Nucleus {ECO:0000269|PubMed:23752197}. Cytoplasm. Note=Predominantly nuclear but localizes to the cytoplasm when expressed with isoform 4.; SUBCELLULAR LOCATION: [Isoform 2]: Nucleus. Cytoplasm. Note=Localized mainly in the nucleus with minor staining in the cytoplasm.; SUBCELLULAR LOCATION: [Isoform 3]: Nucleus. Cytoplasm. Note=Localized in the nucleus in most cells but found in the cytoplasm in some cells.; SUBCELLULAR LOCATION: [Isoform 4]: Nucleus. Cytoplasm. Note=Predominantly nuclear but translocates to the cytoplasm following cell stress.; SUBCELLULAR LOCATION: [Isoform 7]: Nucleus. Cytoplasm. Note=Localized mainly in the nucleus with minor staining in the cytoplasm.; SUBCELLULAR LOCATION: [Isoform 8]: Nucleus. Cytoplasm. Note=Localized in both nucleus and cytoplasm in most cells. In some cells, forms foci in the nucleus that are different from nucleoli.; SUBCELLULAR LOCATION: [Isoform 9]: Cytoplasm.
Interaction partners:
- 14-3-3 protein sigma
- Histone acetyltransferase p300
- Hypoxia-inducible factor 1-alpha
- Histone deacetylase 1
- Heat shock protein HSP 90-alpha
- Serine-protein kinase ATM
- Protein Mdm4
- Serine/threonine-protein kinase Chk2
- Apoptosis regulator Bcl-2
- Bcl-2-like protein 1
Sequence:
MEEPQSDPSVEPPLSQETFSDLWKLLPENNVLSPLPSQAMDDLMLSPDDIEQWFTEDPGPDEAPRMPEAAPPVAPAPAAPTPAAPAPAPSWPLSSSVPSQKTYQGSYGFRLGFLHSGTAKSVTCTYSPALNKMFCQLAKTCPVQLWVDSTPPPGTRVRAMAIYKQSQHMTEVVRRCPHHERCSDSDGLAPPQHLIRVEGNLRVEYLDDRNTFRHSVVVPYEPPEVGSDCTTIHYNYMCNSSCMGGMNRRPILTIITLEDSSGNLLGRNSFEVRVCACPGRDRRTEEENLRKKGEPHHELPPGSTKRALPNNTSSSPQPKKKPLDGEYFTLQIRGRERFEMFRELNEALELKDAQAGKEPGGSRAHSSHLKSKKGQSTSRHKKLMFKTEGPDSD