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 locations: Cytoplasm, Nucleus, Nucleus, PML body, Endoplasmic reticulum, Mitochondrion matrix, Cytoplasm, Cytoskeleton, Microtubule organizing center, Centrosome
Recruited into PML bodies together with CHEK2 . Translocates to mitochondria upon oxidative stress . Translocates to mitochondria in response to mitomycin C treatment . Competitive inhibition of TP53 interaction with HSPA9/MOT-2 by UBXN2A results in increased protein abundance and subsequent translocation of TP53 to the nucleus .
Subcellular locations: Nucleus, Cytoplasm
Predominantly nuclear but localizes to the cytoplasm when expressed with isoform 4.
Subcellular locations: Nucleus, Cytoplasm
Localized mainly in the nucleus with minor staining in the cytoplasm.
Subcellular locations: Nucleus, Cytoplasm
Localized in the nucleus in most cells but found in the cytoplasm in some cells.
Subcellular locations: Nucleus, Cytoplasm
Predominantly nuclear but translocates to the cytoplasm following cell stress.
Subcellular locations: Nucleus, Cytoplasm
Localized mainly in the nucleus with minor staining in the cytoplasm.
Subcellular locations: Nucleus, Cytoplasm
Localized in both nucleus and cytoplasm in most cells. In some cells, forms foci in the nucleus that are different from nucleoli.
Subcellular locations: Cytoplasm
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.