Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The p53 tumor suppressor orchestrates a number of important genes involved in cell-cycle control and apoptosis. Mice deficient for p53 show a high incidence of cancer but are developmentally normal suggesting that compensatory mechanisms exist in embryogenesis and differentiation. The new KET protein is the first mammalian protein with strong homology to p53 in all evolutionary conserved regions. This conservation makes a functional redundancy of the two proteins in cell-cycle control possible. KET is expressed during embryonic development and in certain adult tissues. Among all of the known p53 proteins of different species KET is most closely related to that found in squid. The relationship between KET and the invertebrate p53 protein sheds light on the evolutionary origin of p53. KET appears to be an ancestral p53-related protein in vertebrates with a possible role in development and differentiation while the ubiquitously expressed p53 protein attained its general role as 'guardian of the genome' during evolution.
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PMID:A novel protein with strong homology to the tumor suppressor p53. 931 5

p53 tumor suppressor protein negatively regulates cell growth, mainly through the transactivation of its downstream target genes. As a sequence-specific DNA binding transcription factor, p53 specifically binds to a 20-bp consensus motif 5'-PuPuPuC(A/T) (T/A)GPyPyPyPuPuPuC(A/T)(T/A)GPyPyPy-3'. We have now identified, partially purified, and characterized an additional approximately 40-kDa nuclear protein, p53CP (p53 competing protein), that specifically binds to the consensus p53 binding sites found in several p53 downstream target genes, including Waf-1, Gadd45, Mdm2, Bax, and RGC. The minimal sequence requirement for binding is a 14-bp motif, 5'-CTTGCTTGAACAGG-3' [5'-C(A/T)(T/A)GPyPyPyPuPuPuC(A/T)(T/A)G-3'], which includes the central nucleotides of the typical p53 binding site with one mismatch. p53CP and p53 (complexed with antibody) showed a similar binding specificity to Waf-1 site but differences in Gadd45 and T3SF binding. Like p53, p53CP also binds both double- and single-stranded DNA oligonucleotides. Important to note, cell cycle blockers and DNA damaging reagents, which induce p53 binding activity, were found to inhibit p53CP binding in p53-positive, but not in p53-negative, cells. This finding suggested a p53-dependent coordinate regulation of p53 and p53CP in response to external stimuli. p53CP therefore could be a third member of the p53 family, in addition to p53 and p73, a newly identified p53 homolog. p53CP, if sequestering p53 from its DNA binding sites through competitive binding, may provide a novel mechanism of p53 inactivation. Alternatively, p53CP may have p53-like functions by binding and transactivating p53 downstream target genes. Cloning of the p53CP gene ultimately will resolve this issue.
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PMID:p53CP, a putative p53 competing protein that specifically binds to the consensus p53 DNA binding sites: a third member of the p53 family? 940 85

In HBV related hepatitis it is generally accepted that the liver injury is mediated by an immune response to the virus, since HBV is not directly cytopathic. The first step in cytotoxic T lymphocyte mediated immune reaction in HBV infected mice is the induction of apoptosis. The role of BCL-2, p53 and PCNA (as the main regulators of cell cycle homeostasis) in this process has not been studied. The aim of this pilot study is to estimate immunohistochemically the expression of the BCL-2, p53 and PCNA in a group of HBV infected patients at various stages of the disease. Formalin fixed, paraffin embedded liver biopsies from 5 patients with HBsAG positivity in their serum were used for immunohistochemical study of the expression of BCL-2, PCNA (PC10) and P53 (DO1clone). As the chromogen we used both the DAB and AEC. The results were co-related with the 3 liver biopsies as controls. In the hepatocytes of the all cases (including controls) we did not found any positivity of BCL-2, p53 and PCNA. However the majority of the lymphocytes present in the liver of some cases of HBV infected patients were strongly BCL-2 positive. This preliminary results of very small group of patients could indicate that hepatocytes in the HBV infection are in the quiescent stage as in the controls and that the cell cycle regulation during infection could be controlled by other genes such as bax, bcl-Xs, FAS etc., but further studies are required.
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PMID:Immunohistochemical study of the expression of BCL-2, PCNA and P53 proteins in the patients with hepatitis B. The pilot study. 943

The p53 tumor suppressor gene, which is induced by DNA damage and/or stress stimuli, causes cells to undergo G1-arrest or apoptotic death; thus it plays an essential role in human carcinogenesis. We have searched for p53-related genes by using degenerate PCR, and have identified two cDNA fragments similar to but distinct from p53: one previously reported, p73, and the other new. We cloned two major splicing variants of the latter gene and named these p51A and p51B (a human homologue of rat Ket). The p51A gene encodes a 448-amino-acid protein with a molecular weight of 50.9 kDa; and p51B, a 641-amino-acid protein with a molecular weight of 71.9 kDa. In contrast with the ubiquitous expression of p53, expression of p51 mRNA was found in a limited number of tissues, including skeletal muscle, placenta, mammary gland, prostate, trachea, thymus, salivary gland, uterus, heart and lung. In p53-deficient cells, p51A induced growth-suppression and apoptosis, and upregulated p21waf-1 through p53 regulatory elements. Mutations in p51 were found in some human epidermal tumors.
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PMID:Cloning and functional analysis of human p51, which structurally and functionally resembles p53. 966 64

KET is a member of the newly discovered family of proteins that is related to the tumor suppressor p53. Here we describe the molecular cloning of a human cDNA of 4846 bp encoding a protein of 680 amino acids. The human KET protein shares 98% identity with the previously characterized rat homolog. The remarkably high degree of conservation lends support to the notion that KET proteins have important basic functions in development and differentiation. Using the GeneBridge 4 radiation hybrid panel, we have mapped KET to human Chromosome (Chr) 3q27. KET is located between the somatostatin gene SST (proximal) and the apolipoprotein D gene APOD (distal) in a region of conserved synteny to mouse Chr 16. This chromosomal region is deleted in early stages of tumorigenesis of mouse islet cell carcinomas and contains the hitherto unidentified Loh2 gene, a putative suppressor of angiogenesis. The murine homolog Ket was mapped in an interspecific backcross panel and falls into this region of loss of heterozygosity. From our mapping data we infer that KET might act as a tumor suppressor and is considered as a candidate for Loh2.
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PMID:Cloning and chromosomal mapping of the human p53-related KET gene to chromosome 3q27 and its murine homolog Ket to mouse chromosome 16. 979 41

The newly identified p53 homolog p73 can mimic the transcriptional activation function of p53. We investigated whether p73, like p53, participates in an autoregulatory feedback loop with MDM2. p73 bound to MDM2 both in vivo and in vitro. Wild-type but not mutant MDM2, expressed in human p53 null osteosarcoma Saos-2 cells, inhibited p73- and p53-dependent transcription driven by the MDM2 promoter-derived p53RE motif as measured in transient-transfection and chloramphenicol acetyltransferase assays and also inhibited p73-induced apoptosis in p53-null human lung adenocarcinoma H1299 cells. MDM2 did not promote the degradation of p73 but instead disrupted the interaction of p73, but not of p53, with p300/CBP by competing with p73 for binding to the p300/CBP N terminus. Both p73alpha and p73beta stimulated the expression of the endogenous MDM2 protein. Hence, MDM2 is transcriptionally activated by p73 and, in turn, negatively regulates the function of this activator through a mechanism distinct from that used for p53 inactivation.
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PMID:MDM2 suppresses p73 function without promoting p73 degradation. 1020 51

The role that the p53 tumor suppressor gene product plays in cellular differentiation remains controversial. However, recent evidence indicates that p53 is required for proper embryogenesis. We have studied the effect of p53 on the expression mediated by the promoter of the rat muscle-specific phosphoglycerate mutase gene (M-PGAM), a marker for cardiac and skeletal muscle differentiation. Experiments involving transient transfection, mobility shift assay, and site-directed mutagenesis demonstrated that p53 specifically binds and transactivates the M-PGAM promoter. The p53-related proteins p51A and p73L also transactivated M-PGAM. Moreover, stable expression of a p53 dominant mutant in C2C12 cells blocked the induction of M-PGAM expression during the myoblast to myotube transition and the ability of p53, p51A, and p73L to transactivate the M-PGAM promoter. In addition, impaired expression of M-PGAM was observed in a subset of p53-null animals in heart and muscle tissues of anterior-ventral location. These results demonstrate that p53 is a transcriptional activator of M-PGAM that contributes in vivo to the control of its cardiac expression. These data support previous findings indicating a role for p53 in cellular differentiation.
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PMID:p53 is a transcriptional activator of the muscle-specific phosphoglycerate mutase gene and contributes in vivo to the control of its cardiac expression. 1035 11

p51, a novel family member of human p53, is a recently identified candidate tumor suppressor gene mapped at chromosome 3q28. Like p53, p51 was found to activate p21Waf1/Cip1 and to induce apoptosis. Since the DNA loss at 3q is reported in several cancers including non-small cell lung cancer (NSCLC), we screened for mutations in p51A (TAp63gamma), an isoform of p51 with short C-terminal region, in 80 NSCLCs as well as 85 breast cancers by RT-PCR single strand conformation polymorphism (SSCP) analysis and DNA sequencing. In NSCLCs, p51 was expressed in most tumors at variable levels and we found three missense and one silent mutations: Gln31His (transactivation domain) in two tumors, Ala148Pro (DNA-binding domain) and Leu248Leu (DNA-binding domain). In the tumor with Ala148Pro or the silent mutation, only the mutant gene appeared to be expressed. The modified FASAY method to test the ability of yeast expressing p51A cDNA to grow in medium lacking histidine has revealed that Ala148Pro results in a loss of function, while Gln31His does not. In contrast to NSCLC, no mutation was observed in all 85 breast cancers by the similar method. Our results suggest that, because of infrequent mutation, p51 may not be a Knudson type tumor suppressor in most NSCLCs and breast cancers. Nevertheless, in at least a part of NSCLC, p51 may play a certain role in carcinogenesis in a tissue-specific manner.
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PMID:Mutational analysis of p51A/TAp63gamma, a p53 homolog, in non-small cell lung cancer and breast cancer. 1039 84

We recently discovered human p51, a new gene structurally and functionally related to human p53. This gene encodes two major splicing variants, p51A and p51B, which differ in their carboxyl-terminal structure. However, p51A shows strong transactivation potential, while p51B has only weak potential. To clarify the reason for this difference, we made chimeric gene constructs expressing fusion proteins of p53-p51A and p53-p51B, having an N-terminus of p53 and a C-terminus of p51A or p51B, respectively. In a BAX promoter-luciferase assay using p53-deficient SAOS-2 cells, they exhibited up to 30-fold stronger transactivation potential than p53 and p51A themselves, suggesting that the C-terminus of p51B does not simply serve as a repressor. We obtained similar results with p21WAF1 promoter-reporter plasmids. These chimeras will be valuable tools for gene therapy.
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PMID:Human p53-p51 (p53-related) fusion protein: a potent BAX transactivator. 1042 49

A unique clinical syndrome has been described in which patients have chronic oral ulceration and autoantibodies to nuclei of stratified squamous epithelium. We have characterized the autoantibodies from patients sera and found that the major autoantigen is a 70 kDa epithelial nuclear protein. Sequencing of the cDNA for this protein, chronic ulcerative stomatitis protein, revealed it to be homologous to the p53 tumor suppressor and to the p73 putative tumor suppressor, and to be a splicing variant of the KET gene. The p53-like genes, p73 and the several KET splicing variants, are recently described genes of uncertain biologic and pathologic significance. This study provides the first clear association of a p53-like protein with a disease process.
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PMID:Characterization of an autoantigen associated with chronic ulcerative stomatitis: the CUSP autoantigen is a member of the p53 family. 1046 95


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