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)

Nerve growth factor (NGF) inhibited cellular DNA synthesis of rat T9 anaplastic glioma cells in a dose-dependent manner in the range of 0.5-5 micrograms/ml. Oxidation of 2 to 3 tryptophan residues of NGF, which had been known to destroy biological and immunological activity, greatly diminished its inhibitory effect on DNA synthesis. The inhibition was also abolished by anti-NGF IgG. Flow cytometric analyses and immunocytochemical assays of DNA synthesis using bromodeoxyuridine incorporation at various times during cell exposure to NGF revealed that the growth inhibition was attributable to gradual accumulation of growth-arrested cells at the G1 phase. Synthesis of nuclear regulatory proteins JUN and p53 was inhibited preferentially and progressively by NGF as inhibition of DNA synthesis increased.
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PMID:Growth inhibition of anaplastic glioma cells by nerve growth factor. 129 51

The p53 gene was examined in primary or metastatic tumors from six patients with rhabdomyosarcoma (RMS) and in five RMS cell lines by screening methods including single-strand conformation polymorphism analysis, the RNase protection assay, sequencing of complementary DNA subclones, and Southern blotting. Six original tumors were of embryonal histology, four alveolar, and one mixed. p53 mutations were identified in four of the six tumors or cell lines derived from tumors with embryonal histology and in one of the four with alveolar histology. Consistent with p53 allele loss, each mutation was found in the homo- or hemizygous state. One tumor showed a G to C transversion at p53 codon 213 (arginine to proline), and another showed deletion of the entire gene. The p53 mutations in cell lines included a codon 248 C to T transition (arginine to tryptophan) in RD and a codon 280 A to T transversion (arginine to serine) in RH30. The cell line CTR contained a 4-base pair deletion at codons 219/220 in exon 6 with resultant frame shift and premature termination in exon 7. These data support the role of diverse types of p53 mutations in the pathogenesis and/or progression of a significant proportion of cases of childhood RMS.
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PMID:Frequency and diversity of p53 mutations in childhood rhabdomyosarcoma. 155 27

Recent studies have suggested that the p53 oncoprotein might function normally as a tumor suppressor. Mutations in highly conserved regions of the p53 gene have been observed in numerous types of tumors and tumor cell lines. To detect in a more sensitive manner p53 gene mutations in small cell lung cancer (SCLC) we utilized the single strand conformation polymorphism (SSCP) technique of Orita et al., (1989). Using PCR primers for the most highly conserved regions of the p53 gene, including exons 4-9, we have identified p53 mutations in 5 of 9 small cell lung cancer (SCLC) tumor DNA samples and in 1 SCLC cell line. None of the mutations seen in tumor DNA samples were present in normal DNA from the same patients, indicating that mutation of the p53 gene in these tumors was a somatic event. Of the six mutations observed, two were found in exon 7, three were found in the region encompassing exons 8 and 9, and one was found in the region encompassing exons 5 and 6. Nucleotide sequencing of one of the exon 7 mutations and one of the exon 8-9 mutations indicated that each was a C to T transition. In SCLC-6 the mutation resulted in substitution of serine for proline at amino acid 278 and in SCLC-4 substitution of tryptophan for arginine at amino acid 248, both nonconservative amino acid substitutions. Both of these changes are in regions of the p53 gene where mutations have been observed in other tumors. Two additional mutations were observed in SCLC cell lines using conventional PCR techniques. One of these is a mutation which results in altered splicing of the p53 pre-mRNA.
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PMID:Use of the single strand conformation polymorphism technique and PCR to detect p53 gene mutations in small cell lung cancer. 164 2

Nine metastatic melanoma cell lines and two melanocyte cell lines were analyzed for point mutations in highly conserved regions of the p53 gene. No mutations were detected in the two melanocytic cell lines and in eight melanoma cell lines. However, a C----T transition at codon 248, resulting in a substitution of tryptophan for arginine, was found in one melanoma cell line. On immunohistochemical staining, only this cell line showed reactivity for mouse monoclonal antibody 1801, which is immunoreactive with human p53 protein. The original paraffin-embedded specimen from which this mutant cell line was established was obtained, and sequence analysis detected the identical mutation in the p53 gene as that seen in the derived cell line. This is the first report indicating point mutations in the p53 gene in malignant melanocytic tissues.
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PMID:Mutational analysis of the human p53 gene in malignant melanoma. 192 72

Partial sequence determinations were performed on exon 8 of tumour suppressor gene p53 of cattle, sheep, goat, horse and pig. High sequence homology between these species and other species including dog, cat, chicken and man is demonstrated. A mutation CGG-->TGG (arginine-->tryptophan) was detected in a feline solid carcinoma of the mammary gland.
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PMID:Sequence of an exon of tumour suppressor p53 gene--a comparative study in domestic animals: mutation in a feline solid mammary carcinoma. 764 Sep 60

Exon 8 of tumour suppressor gene p53 was sequenced in domestic cats and showed remarkable similarity to the human sequence. Only four of the 13 nucleotide differences gave rise to interspecific amino acid differences. In an investigated lymphosarcoma we detected a mutation cgg --> tgg (arginine --> tryptophan) in codon no. 282.
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PMID:Sequence of an exon of the feline p53 gene--mutation in a lymphosarcoma. 822 Oct 43

We have sequenced p53 in three colon cancer cell lines capable of autonomous proliferation. SNU-C1 and SNU-C4 cells, whose autonomous growth is dependent upon autocrine stimulation of epidermal growth factor receptor (EGFR), had wildtype p53 sequence of exons 4-9. In contrast, an EGFR ligand-independent cell line, SNU-C5, had heterozygous missense mutations affecting codons 218 (valine to leucine) and 248 (arginine to tryptophan) of p53. Bacterial cloning of p53 from SNU-C5 cells showed that the 248trp and 218leu mutants were both expressed and on separate alleles. 248trp is a common 'hot spot' mutant of p53 with variable dominant negative activity depending on the celullar context. Valine 218, in contrast, is rarely affected by mutation in cancers and is located in a region of the hydrophobic core domain away from 'hot spot' DNA contact sights. However, valine 218 is completely conserved across species, prompting us to investigate the function of 218leu in SNU-C5 cells. SNU-C5 cells exhibited complete loss of normal p53 function as evidenced by over-expression of p53 protein and by failure to show induction of p53, waf-1, mdm-2 or G1/S arrest in response to the DNA damaging agent, bleomycin. In a yeast p53 functional assay (FASAY), 50% of the clones were unable to transactivate a p53-specific promoter required for yeast colony expansion at 25, 30 or 37 degrees C. Sequencing of the p53 insert from several randomly selected wild-type and mutant yeast clones revealed that 218leu-bearing clones retained their ability to transactivate the p53-specific promoter. As expected, the 248trp-bearing clones lost this function. These data indicate that although 218leu retains normal transactivation activity on a p53 promoter in yeast at physiological temperatures, it is not capable of normal p53 function in the presence of a 248trp allele in SNU-C5 cells. It remains unclear whether the strong dominant negative activity of 248trp in SNU-C5 cells is related to the cellular context or to an unresolved abnormality of 218leu function.
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PMID:p53 functional loss in a colon cancer cell line with two missense mutations (218leu and 248trp) on separate alleles. 855 7

Human p21 (also known as WAF1, CIP1, or SDI1) is a dual inhibitor of cyclin dependent kinases (CDKs) and the replication factor PCNA, which plays a role as a downstream mediator of the cell-cycle arrest induced by the tumor suppressor p53. To determine whether inactivation of downstream targets of p53 might contribute to cellular transformation, we have examined the integrity of the p21 gene in 36 invasive ductal breast carcinomas. Direct sequence analysis of the polymerase chain reaction-amplified p21 gene revealed a C to T transition in codon 94 that caused the substitution of a tryptophan for an arginine in a tumor specimen. This mutation was not detected in normal DNA extracted from the same patient nor in a polymerase chain reaction-restriction fragment length polymorphism of 50 unrelated individuals, indicating that it corresponds to a tumor-specific alteration. Functional analysis of the p21(R94W) protein produced in different eukaryotic and prokaryotic expression systems revealed that this mutation impaired the ability of p21 to inhibit CDKs. By contrast, the R94W mutant was unaltered in its ability to promote cyclin-CDK association as well as in its ability to bind proliferating cell nuclear antigen, thus leaving its putative functions as kinase activator or as inhibitor of replicative DNA synthesis intact. On the basis of these functional analysis, we propose that the Arg residue at position 94 is important for the CDK inhibitory role of p21.
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PMID:Functional analysis of a p21WAF1,CIP1,SDI1 mutant (Arg94 --> Trp) identified in a human breast carcinoma. Evidence that the mutation impairs the ability of p21 to inhibit cyclin-dependent kinases. 866 32

Highly conserved regions of the tumour suppressor gene p53, including the typical human tumour hot spots (codons 175, 245, 248, 249, 273 and 282), were investigated in various canine neoplasms. A mutation CGG-->TGG (arginine-->tryptophan) was detected in codon 249 in an adenoma of the circumanal gland.
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PMID:Canine tumour suppressor gene p53--mutation in a case of adenoma of circumanal glands. 923 81

Five cases of adenoid basal carcinoma (ABC) of the uterine cervix were examined for the presence of p53 tumor suppressor gene, K-ras-2 oncogene, and human papillomavirus (HPV). A topographic genotyping approach was used to search for point mutations in K-ras-2 (exon 1 and 2) and p53 (exons 5 to 8) in archival formalin-fixed tissue blocks. Minute target sites were selected from polymerase chain reaction (PCR) amplified and directly sequenced tissue sections. Tissue sections were additionally subjected to immunohistochemical staining for p53 and WAF-1 protein. Because wild type p53 induces WAF-1 gene expression, immunohistochemical staining for WAF-1 protein using monoclonal antibodies may serve as an indirect means to test for p53 mutational damage. Mutational genotype was compared to histopathologic features and immunohistochemical staining. To study the role of HPV, L1 region consensus primers were used to amplify topographic samples, followed by HPV genotyping by direct sequencing and comparison to known viral strains. ABC was found to contain HPV in all cases, proven by genotyping to be HPV type 16 in each case. The virus showed no evidence of genomic variation from prototype HPV type 16 in the L1 segment examined. No K-ras-2 point mutations were identified. p53 immunopositivity was present in all tumors, being weak and focal in 4 and strong and diffuse in 1. WAF-1 immunostaining was positive in two tumors showing weak focal p53 immunopositivity. The single strong and diffuse p53 immunopositive tumor was negative for WAF-1 and was shown to contain a missense p53 point mutation (exon 7-codon 248 tryptophan). In conclusion, ABC is characterized by the presence of HPV type 16. K-ras-2 point mutation appears to play no role in the development of this tumor. p53 gene alterations are common including wild type hyperexpression (weak focal p53 immunopositivity, WAF-1 positivity, no mutational change) and p53 point mutational damage.
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PMID:The origin and molecular characterization of adenoid basal carcinoma of the uterine cervix. 942 Oct 66


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