STRING | IntAct | MINT

Open Targets | OMIM

Catalytic Site Atlas

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Cytoplasm,Nucleus,Nucleus,PML body,Endoplasmic reticulum,Mitochondrion matrix;Isoform 1: Nucleus,Cytoplasm;Isoform 2: Nucleus,Cytoplasm;Isoform 3: Nucleus,Cytoplasm;Isoform 4: Nucleus,Cytoplasm;Isoform 7: Nucleus,Cytoplasm;Isoform 8: Nucleus,Cytoplasm;Isoform 9: Cytoplasm;

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 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).

GO:0005737; GO:0005829; GO:0005783; GO:0005622; GO:0005759; GO:0005739; GO:0000790; GO:0016363; GO:0005730; GO:0005654; GO:0005634; GO:0016605; GO:0032991; GO:0005667; GO:0005524; GO:0051087; GO:0003682; GO:0005507; GO:0001046; GO:0097718; GO:0003677; GO:0001228; GO:0003700; GO:0000981; GO:0019899; GO:0035035; GO:0042826; GO:0042802; GO:0003730; GO:0002039; GO:1990841; GO:0002020; GO:0046982; GO:0019901; GO:0047485; GO:0051721; GO:0019903; GO:0043621; GO:0030971; GO:0000980; GO:0000978; GO:0001085; GO:0001094; GO:0008134; GO:0044212; GO:0031625; GO:0008270; GO:0006914; GO:0006284; GO:0007569; GO:0007050; GO:0030154; GO:0008283; GO:0034613; GO:0072717; GO:0006974; GO:0035690; GO:0071480; GO:0042149; GO:0071456; GO:0071479; GO:0034644; GO:0031497; GO:0048512; GO:0019221; GO:0008340; GO:0030330; GO:0006977; GO:0006978; GO:0000733; GO:0043153; GO:0006983; GO:0097193; GO:0072332; GO:0042771; GO:0031571; GO:0009299; GO:0007275; GO:0043066; GO:0030308; GO:0008285; GO:0048147; GO:0051097; GO:0051974; GO:0000122; GO:0045892; GO:0006289; GO:0097252; GO:0090403; GO:0043065; GO:0071158; GO:1900119; GO:0010628; GO:2001244; GO:0050731; GO:1902895; GO:1903800; GO:0046827; GO:1900740; GO:0032461; GO:2000379; GO:0090200; GO:0045899; GO:0070245; GO:0045944; GO:1990440; GO:0045893; GO:0016579; GO:0051289; GO:0008104; GO:0051262; GO:0065003; GO:0007265; GO:0042981; GO:1902749; GO:0046902; GO:1901796; GO:0006355; GO:0090399; GO:0046677; GO:0010332; GO:0051123; GO:0072331; GO:0016032