WIREDiCON Gene Information Demonstration

Official Symbol : TP53provided by HGNC
Official Full Name : tumor protein p53 (Li-Fraumeni syndrome)provided by HGNC
Primary source : HGNC:11998
See related : Ensembl:ENSG00000141510; HPRD:01859; MIM:191170
Gene type : protein coding
RefSeq status : Validated
Organism : Homo sapiens
Lineage : Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as : p53; LFS1; TRP53
Summary
Tumor protein p53, a nuclear protein, plays an essential role in the regulation of cell cycle, specifically in the transition from G0 to G1. It is found in very low levels in normal cells, however, in a variety of transformed cell lines, it is expressed in high amounts, and believed to contribute to transformation and malignancy. p53 is a DNA-binding protein containing DNA-binding, oligomerization and transcription activation domains. It is postulated to bind as a tetramer to a p53-binding site and activate expression of downstream genes that inhibit growth and/or invasion, and thus function as a tumor suppressor. Mutants of p53 that frequently occur in a number of different human cancers fail to bind the consensus DNA binding site, and hence cause the loss of tumor suppressor activity. Alterations of the TP53 gene occur not only as somatic mutations in human malignancies, but also as germline mutations in some cancer-prone families with Li-Fraumeni syndrome.

Protein Interaction
1.Tumor suppressor protein p53 displays 3' --> 5' exonuclease activity, and interaction of p53 with HIV-1 reverse transcriptase (RT) can provide a proofreading function for HIV-1 RT
2.Assays with phage-displayed Nef from HIV-1 NL4-3 have been used to identify a series of guanidine alkaloid-based inhibitors of Nef interactions with p53, actin, and p56(lck)
3.HIV-1 Nef binds directly to tumor suppressor protein p53; an N-terminal 57-residue fragment of Nef (Nef 1-57) contains the p53-binding domain
4.When expressed in astrocytes, neurons, and non-glial 293T cells, HIV-1 Tat interacts with a number of cell cycle-related proteins including cyclin A, cyclin B, cyclin D3, Cdk2, Cdk4, Cdk1/Cdc2, cdc6, p27, p53, p63, hdlg, and PCNA
5.Supernatants from HIV-1 Tat-transfected monocytoid cells induces p53 expression in neurons, indicating a role for Tat in the neuropathogenesis of HIV-1
6.HIV-1 Tat inhibits p53-responsive transcription by binding to histone acetyltransferases and repressing the acetylation of p53 on residue Lys-320, alluding to a mechanism whereby Tat may impair p53 functions, thus favoring the establishment of neoplasia
7.HIV-1 Tat and p53 cooperate in the activation of HIV-1 gene expression in SaOS2 cells
8.Wild-type p53 is a potent inhibitor of HIV-1 Tat transactivation of the HIV-1 LTR promoter in Jurkat T cells and Hep3B cells
9.HIV-1 Tat downregulates the expression of p53, suggesting a mechanism for HIV-1-mediated transformation of infected cells
10.HIV-1 Tat binds to p53, an interaction mediated by the basic region of Tat (amino acids 49-57) and the acidic O2 domain of p53 (amino acids 341-354
11.Activation of p21/Waf1/Cip1 by HIV-1 Vpr appears to be regulated by p53
12.Overexpression of p53 decreases the level of activation of the viral LTR promoter by HIV-1 Vpr
13.HIV-1 Vpr interacts with p53 in a complex with the transcription factor Sp1 that modulates viral gene transcription from the HIV-1 LTR promoter
14.Results from GST pull-down assays show the association of Vpr with p53 in extracts containing Sp1, suggesting the physical interaction of Vpr with Sp1 and p53 could modulate transcriptional activity of p21
15.HIV-1 Vpr can neutralize inhibitory effects of the human homologue of yeast Rad23 protein A (hHR23A) on p53, thereby activating p53 transcriptional activity

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