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)

In the present study, we analysed human choriocarcinoma cell lines for abnormalities in the tumour-suppressor gene p53 by Southern blotting, Northern blotting, non-radioisotopic single-stranded conformational polymorphism (SSCP) and complementary DNA sequencing. In all cell lines (Bewo, GCH-1, GCH-2, SCH, JAR, JEG-3, NUC-1 and HCCM-5), no p53 gene abnormality was detected by using Southern blotting. p53 mRNA of the expected size was detected in all cell lines tested by Northern blotting. SSCP analysis revealed abnormalities of p53 cDNA in the SCH cell line. Sequencing analysis of the entire coding region of the p53 gene revealed that both alleles were expressed in the JEG-3 cell line, and one of the alleles contained a point mutation (G to T) in codon 167 (Gln to His). In the NUC-1 cell line both alleles were point mutated. One allele had a point mutation (A to T) that resulted in a codon 17 change (Glu to Asp), and another had a point mutation (A to T) that caused a codon 24 change (Lys to Asn). In the SCH cell line, AGG was inserted between codon 249 and 250; this insertion resulted in an abnormal structure of the p53 protein. In three out of eight human choriocarcinoma cell lines, a p53 gene abnormality was detected. Therefore our data demonstrate that p53 gene abnormalities are associated with choriocarcinoma cell lines.
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PMID:Analysis of the p53 gene in human choriocarcinoma cell lines. 781 56

Grilled or fried meat and fish contain various mutagenic heterocyclic amines, and structures of at least 19 compounds have already been determined. Among these, 10 have been examined for long term carcinogenicity, all proving to be positive. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), for example, preferentially induced mammary adenocarcinomas in 47% of Fischer 344 female rats when supplemented into the diet at a concentration of 400 parts per million (ppm) for 52 weeks. Moreover, 100 ppm of PhIP for 104 weeks yielded the same incidence. PhIP in the diet for 48 weeks also induced mammary cancer in Sprague-Dawley female rats with incidences of 72 and 25% at 200 ppm and 100 ppm. 2-Amino-3,4-dimethylimidazo[4,5-f]quinoline in the diet at 300 ppm also induced a 25% incidence of mammary adenocarcinomas within 40 weeks. Analysis of PhIP-induced rat mammary carcinomas for ras mutations by polymerase chain reaction-single-strand conformation polymorphism and direct sequencing revealed Ha-ras activation in 3 of 17 carcinomas; all were G-->A transitions at the second letter of codon 12 replacing glycine by glutamic acid. A p53 gene mutation was also found in 1 of 10 carcinomas examined; a G-->T transversion was detected at the third letter of codon 130, with a substitution of asparagine for lysine. PhIP is the most abundant mutagenic and carcinogenic heterocyclic amine in grilled meat, and, therefore, a role for this compound in human carcinogenesis is strongly implied.
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PMID:Dietary carcinogens and mammary carcinogenesis. Induction of rat mammary carcinomas by administration of heterocyclic amines in cooked foods. 803 40

ERGIC-53 (former designation, p53) is a 53-kDa nonglycosylated, dimeric, and hexameric type I membrane protein that has been established as a marker protein for a tubulovesicular intermediate compartment in which protein transport from the endoplasmic reticulum to the Golgi apparatus is blocked at 15 degrees C. Although ERGIC-53 is not a resident protein of the rough endoplasmic reticulum its cDNA sequence carries a double lysine endoplasmic reticulum retention motif at the cytoplasmically exposed COOH terminus. Here we report that overexpression of ERGIC-53 in COS cells saturates its intracellular retention system leading to the appearance of ERGIC-53 at the cell surface. Cell surface ERGIC-53 is efficiently endocytosed by a mechanism that is disturbed when the two critical lysines of the endoplasmic reticulum retention motif are replaced by serines. The results suggest a mechanistic similarity of pre-Golgi retention by the double lysine motif and lysine-based endocytosis.
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PMID:A dual role for COOH-terminal lysine residues in pre-Golgi retention and endocytosis of ERGIC-53. 811 75

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant of the heterocyclic amines, a group of potent carcinogens contained in cooked meat and fish. Female F344 rats fed a diet containing 100 or 400 ppm PhIP developed mammary carcinomas within 104 or 52 wk, respectively, at the rate of 47% for each group; these carcinomas were examined for mutations in three members of the ras gene family and in the p53 gene. Single-strand conformation polymorphism (SSCP) analysis and direct sequencing demonstrated a G-->A transition at the second position of Ha-ras codon 12, with the resultant substitution of glutamic acid for glycine, in two of 10 carcinomas induced by 100 ppm PhIP and in one of seven induced by the 400 ppm dose. No mutations in Ki-ras or N-ras were detected. cDNA polymerase chain reaction-SSCP analysis and direct sequencing demonstrated a G-->T transversion at the third position of p53 codon 130, with the resultant substitution of asparagine for lysine, in one of the 10 carcinomas induced by 100 ppm of PhIP for which freshly frozen samples were available. PhIP-induced rat mammary carcinogenesis can be regarded as a unique system in that rat mammary carcinomas are negative for ras and p53 mutations.
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PMID:Infrequent mutation of Ha-ras and p53 in rat mammary carcinomas induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. 818 28

We investigated the expression of p53 in paraformaldehyde-lysine-periodate fixed normal and chronic myelogenous leukemia (CML) hemopoietic cells with flow cytometry and two monoclonal antibodies, PAb1801 and the mutant-conformation-associated PAb240. With both antibodies p53 proteins were detected in more than 50% of CD34+ cells and in more than 95% neutrophils but were undetectable in the CD34- myeloid precursors. The expression of a p53 protein reactive with PAb240 was closely associated with CD34+/HLA-DR+ cells and with cells in active cell cycle, while the p53 protein recognized by PAb1801 was mainly found in CD34+/HLA-DR- cells and in cells in the G0/G1 phases of the cell cycle. Treatment of chronic-phase CML cells with p53 antisense oligonucleotides resulted in significantly increased numbers of granulocyte-macrophage colony-forming unit colonies in 12 of 17 cases studied. Slightly reduced granulocyte-macrophage colony-forming unit colony numbers were observed in one case and no change in the four others. In eight samples of normal bone marrow cells, treatment with antisense oligonucleotides showed no consistent changes in granulocyte-macrophage colony-forming unit numbers. Our data suggest that the expression of the tumor suppressor p53 is involved in the regulation of both normal and CML hemopoiesis and that the inhibition of p53 expression could modulate the proliferation of CML hemopoietic cells and possibly of normal cells.
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PMID:The involvement of "tumor suppressor" p53 in normal and chronic myelogenous leukemia hemopoiesis. 827 97

In this study, rat embryo lung organ cultures were exposed to benzo[a]pyrene (B[a]P). After carcinogen-treatment the cells were dissociated and an epithelial cell line (BP) was developed from the primary cell culture derived from the carcinogen-treated explants. Investigations were performed on the sequential changes occurring in the course of neoplastic progression of BP cells and in the tumor cells that arose in vivo from implanted BP cells. During the neoplastic progression a mutation was shown to occur in p53 gene at codon 130 (AAG > AGG; Lys > Arg) in a single cell which expanded and gave rise to a predominant subpopulation. This mutational event was already detected at passage 14 but was probably not a direct consequence of a specific alteration caused by the carcinogen in the target cell. This mutation was retained through the subsequent progressional steps first as a heterozygous mutation, then converted to a homozygous state. From passage 18 on, it was possible in BP cell cultures to detect foci of larger morphologically distinct cells emerging on a background of cells maintaining the original morphology. These foci were shown to derive from a single cell carrying the p53 mutation in a homozygous state. During the neoplastic progression the mutant p53 allele frequency steadily increased and this mutant allele eventually came to predominate completely in the late stages of the neoplastic progression, including in the transplantation-induced tumors. The pattern of a directional selection for mutant p53 gene towards fixation is probably applicable to a wide range of human malignancies and may reflect the particular importance of this gene for tumorigenesis.
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PMID:Directional selection associated with clonal expansion of p53 mutant cells during neoplastic development of carcinogen-treated rat embryo lung epithelial cells. 830 88

The recent finding that eight out of 10 multiple myeloma cell lines have p53 gene mutations prompted us to examine the p53 tumour suppressor gene in 25 non-related multiple myeloma patients. None of 19 patient bone marrow samples available for Southern blot analysis showed rearrangements in the p53 gene and only one patient showed loss of the p53 locus. DNA encompassing exons 5, 7, and 8, where p53 mutations commonly cluster, was amplified by PCR. Single-strand conformation polymorphisms of the PCR-amplified exon 5 region were detected in two patients. Direct sequencing of the mutant band revealed that one patient had a C to T transition at codon 138 (Ala to Val) and one patient had a G to C transversion at codon 139 (Lys to Asn). p53 mutations in germline cells in hereditary cancer syndromes predispose the family members to the development of malignancies. We therefore searched for p53 germline mutations in exons 5, 7, and 8 in the affected individuals from three families each with two multiple myeloma patients (these patients include three individuals from the non-related group mentioned above). Using Southern blotting, polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing, no germline mutations were found. These results indicate that mutations in exons 5, 7, and 8 of the p53 gene are infrequent in multiple myeloma.
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PMID:Sporadic mutations of the p53 gene in multiple myeloma and no evidence for germline mutations in three familial multiple myeloma pedigrees. 832 Oct 49

Mutation of the p53 tumor suppressor gene frequently occurs in a variety of tumors including lung, breast, gastrointestinal, and brain, as well as lymphomas-leukemias. Neuroblastoma, one of the most common solid tumors in childhood, often has amplification of the N-myc gene. We examined for mutations of the p53 tumor suppressor gene by single-strand conformational polymorphism using polymerase chain reaction products and direct sequencing method in neuroblastoma; in addition, we assessed the relationship between p53 mutation and N-myc gene amplification in the disease. Of 86 DNA samples from patients with neuroblastoma, two mutations (2%) were found in the coding region of the p53 gene. Each mutation caused a substitution of amino acid residues. One mutation was located in exon 5, and another was in exon 6. N-myc gene was amplified in 26% of the samples. No p53 mutations were found in neuroblastoma samples with N-myc amplification. In the two individuals, p53 mutations appeared as their disease became more progressive. The neurofibromatosis 1 (NF1) gene is frequently abnormal in another neural disorder, neurofibromatosis type 1; in addition, a potential mutational hot spot of NF1 at lysine at codon 1423 has been identified in several types of tumors. Using single-strand conformational polymorphism, we were unable to detect an abnormality in this region of NF1 in 50 samples of neuroblastoma. The data suggest that p53 mutations occasionally are associated with progression of neuroblastomas, and tumorigenetic influences of mutant p53 may differ from those of N-myc.
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PMID:Mutation of the p53 gene in neuroblastoma and its relationship with N-myc amplification. 835 34

T lymphocytes recognize their antigenic targets as peptides associated with major histocompatibility complex molecules. The HLA-A11 allele, a preferred restriction element for Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocyte responses, presents an immunodominant epitope derived from the EBV nuclear antigen 4. Subpicomolar concentrations of a synthetic nonamer peptide, IVTDFSVIK, corresponding to amino acids 416-424 of the EBV nuclear antigen 4 sequence, can sensitize phytohemagglutinin-stimulated blasts to lysis by EBV-specific HLA-A11-restricted cytotoxic T-lymphocytes. We show that micromolar concentrations of this peptide induce assembly and surface expression of HLA-A11 in an A11-transfected subline of the peptide transporter mutant cell line T2. Using the IVTDFSVIK peptide and a series of synthetic nonamer peptides, differing from the original sequence by single amino acid substitutions, we have defined a motif for HLA-A11-binding peptides. This predicts the presence of a hydrophobic amino acid in position 2, amino acids with small side chains in positions 3 and 6, and a lysine in position 9. Using this motif, we have identified a peptide in the carboxyl-terminal end of wild-type p53, ELNEALELK, which is able to induce HLA-A11 assembly as efficiently as the IVTDFSVIK viral peptide.
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PMID:An HLA-A11-specific motif in nonamer peptides derived from viral and cellular proteins. 838 18

The p53 gene was examined in a series of formalin-fixed paraffin-embedded astrocytic neoplasms of various types by polymerase chain reaction (PCR), single-strand conformation polymorphism analysis (SSCP), and direct sequencing of amplified DNA. PCR primers were designed to amplify three DNA fragments encompassing exons 5, 7, and 8 with splice sites, including all four mutational "hot spots" within this gene. SSCP was performed in a polyacrylamide gel containing 10% glycerol. Two mutations were found among the 20 high and intermediate grade adult astrocytomas studied by this sensitive screening technique and confirmed by sequencing of the PCR product. (1) An anaplastic astrocytoma disclosed a T-A transversion in Codon 246 giving rise to a methionine to lysine amino acid substitution. (2) A giant cell glioblastoma disclosed a G to A transition in Codon 285 resulting in a glutamic acid to lysine substitution. Both mutations were associated with loss of the normal allele. Twenty-three DNA fragments that disclosed no mutation by SSCP analysis were confirmed to be negative by direct sequencing of amplified DNA. No mutations were detected in a series of eight juvenile cerebellar astrocytomas, a biologically distinct form of low-grade astrocytoma. Mutations of the p53 gene may play an important pathogenetic role in a subset of human astrocytomas.
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PMID:Mutations in the p53 gene in human astrocytomas: detection by single-strand conformation polymorphism analysis and direct DNA sequencing. 841 89


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