lmmol · Proteins

Cellular tumor antigen p53

UniProt P04637 Organism Homo sapiens Gene P53, TP53

Also known as: P53, TP53

Function

Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence. Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Negatively regulates cell division by controlling expression of 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.

Classification

Family (Pfam)
PF00870 P53, PF08563 P53_TAD, PF07710 P53_tetramer, PF18521 TAD2
InterPro
p53-like_TF_DNA-bd_sf, p53/RUNT-type_TF_DNA-bd_sf, P53_central_site, p53_DNA-bd, p53_TAD2, p53_tetramer_sf, p53_tetrameristn, p53_transactivation_domain, p53_tumour_suppressor
Functional cluster
Homeobox & Zinc-Finger Transcription Factors

Experimental structures · PDB · 295

A predicted model is available from AlphaFold.

Gene Ontology · 115

Disease associations

Drugs targeting this protein · 5

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 225 cited papers

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