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 gene was examined in primary lymphoblasts of 25 pediatric patients with acute lymphoblastic leukemia by the RNase protection assay and by single strand conformation polymorphism analysis in 23 of 25 cases. p53 mutations were found to occur, but at a low frequency (4 of 25). While all four mutations were identified by single strand conformation polymorphism, the comparative sensitivity of RNase protection was 50% (2 of 4). Heterozygosity was retained at mutated codons in 3 of 4 cases. One pedigree was consistent with the Li-Fraumeni syndrome, and bone marrow from both diagnosis and remission indicated a germline G to T transversion at codon 272 (valine to leucine). Although members of another family were affected with leukemia, a 2-bp deletion in exon 6 was nonhereditary. The other two nonhereditary p53 mutations included a T to G transversion at codon 270 (phenylalanine to cysteine) and a G to C transversion at codon 248 (arginine to proline). These data support the role of both hereditary and acquired p53 mutations in the pathogenesis and/or progression of some cases of childhood acute lymphoblastic leukemia.
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PMID:Hereditary and acquired p53 gene mutations in childhood acute lymphoblastic leukemia. 173 52

SV40 mutants bearing either amino acid substitution or in-frame deletion/insertion mutations in a region of the gene for large T antigen encoding a stretch of hydrophobic residues were analyzed for their behavior in permissive and nonpermissive cells. One of the mutants, with an Ile(573)-Phe substitution had a phenotype indistinguishable from that of wild-type SV40. The remaining three mutants were not viable and were defective for DNA replication. In addition, they displayed a cell-type specificity with respect to transformation; namely, they transformed the mouse C3H10T1/2 cell line, although with a reduced efficiency relative to wild-type, but were unable to transform the rat REF52 cell line. None of the T antigens from the defective mutants formed a complex with the cellular protein p53, indicating that the T-antigen-p53 complex is not required for the transformation of C3H10T1/2 cells.
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PMID:Mutants with changes within or near a hydrophobic region of simian virus 40 large tumor antigen are defective for binding cellular protein p53. 253 98

SV40 large T antigen is phosphorylated at up to ten different amino acids clustered in an N-terminal and a C-terminal part of the polypeptide chain. The N-terminal phosphorylated residues include Ser 123 and Thr 124. We have analyzed the oligomerization, the complex formation with the cellular oncoprotein p53 and the DNA-binding properties of T antigen from two different SV40 transformed cell lines which have either an amino acid exchange at Ser 123 to Phe (W7) or Thr 124 to Ile (D29). In comparison to wild-type T antigen both mutant T antigens have a slightly reduced binding affinity for both binding sites, I and II, of SV40 DNA. Phosphorylation at both residues of T antigen is not essential for formation of the complex with p53. Only the phosphorylation at Thr 124 seems to be critical for the formation of high molecular mass oligomers. Our data support the hypothesis that the oligomerization of T antigen seems to be implicated in viral DNA replication.
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PMID:The phosphorylation at Thr 124 of simian virus 40 large T antigen is crucial for its oligomerization. 304 Apr 70

An investigation of p53 gene mutation by single-stranded conformation polymorphism analysis of polymerase chain reaction products followed by direct sequencing and of murine double minute 2 (mdm-2) gene amplification by Southern blot analysis was performed, using a series of hamster pancreatic duct adenocarcinomas: 18 primary adenocarcinomas induced by N-nitrosobis(2-oxopropyl)amine, a transplantable adenocarcinoma (HPD), and three cell lines derived from HPD (HPD1NR, HPD2NR, and HPD3NR). A mutation in the p53 gene was detected at codon 197, resulting in an amino acid change from leucine to phenylalanine, in both HPD and the three cell lines but in none of the 18 primary adenocarcinomas. In the three HPD cell lines, which were confirmed to contain only cancer cells, a normal p53 gene allele was retained. Immunohistochemical investigation of p53 expression using polyclonal antibody Ab-7 revealed positive nuclear staining in the HPD and two back-transplanted tumors derived from HPD1NR and HPD2NR but not in the 18 primary adenocarcinomas. mdm-2 gene amplification was not detected in 18 primary adenocarcinomas or any of the tumor cell lines. The results suggest that a p53 gene mutation without allelic loss, together with overexpression of p53 protein, may be a genetic alteration involved in the progression stage of multistep pancreatic carcinogenesis in hamsters and that mdm-2 gene amplification is not important for this process.
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PMID:p53 mutation without allelic loss and absence of mdm-2 amplification in a transplantable hamster pancreatic ductal adenocarcinoma and derived cell lines but not primary ductal adenocarcinomas in hamsters. 764 65

Expression of p53 protein, c-erbB-2 protein, neuron-specific enolase (NSE), Phe 5, chromogranin, laminin and collagen type IV was studied by immunohistochemistry in formalin-fixed and paraffin-embedded specimens from 20 patients with renal pelvic carcinoma. Positive membrane-bound c-erbB-2 staining was not found in any case. Two tumors stained for p53 protein. Focal immunoreactivity for laminin was present in 55% and for collagen type IV in 80%. 25% of the cases were NSE positive. None of the tumors stained for Phe 5 or chromogranin. The results were compared with the clinical outcome and the immunohistological findings of p53 protein and c-erbB-2 protein in 13 cases of bladder carcinoma in the same patient group. Four of the thirteen bladder cancer specimens, but only 2 of the 20 renal pelvic cancer specimens, expressed p53 protein. As for renal pelvic carcinoma, c-erbB-2 protein was not expressed in bladder carcinoma. We conclude that p53 gene abnormalities may be of importance in the development of carcinoma in the renal pelvis and urinary bladder, but c-erbB-2 protein expression does not play a major role.
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PMID:Transitional cell carcinoma of the renal pelvis and its expression of p53 protein, c-erbB-2 protein, neuron-specific enolase, Phe 5, chromogranin, laminin and collagen type IV. 771 33

The growth arrest mediated by p53 is caused at least in part by the p53 mediated expression of p21 (p21waf1/Cip1). Since only one-third of primary Burkitt's lymphomas (BL) demonstrate mutations in the p53 gene, we examined the structural integrity of the p21 coding region by single-strand conformational polymorphism and DNA sequence analysis to determine the extent to which this gene is mutated in BL. Of 34 BLs analyzed, a frequent change (38%) at codon 31 that replaced Ser with Arg was found in 13 samples, 10 of which were from Africa. This change at codon 31 is also detected in peripheral blood DNA from normal subjects and may thus represent a polymorphism. One BL cell line, DH978, carried a change at codon 63: Phe to Leu. This mutation was heterozygous, and both the wild-type and the mutated p21 mRNA were expressed in the tumor cell line. By transfection experiments, the mutant p21 was less efficient in suppressing clonogenicity than wild-type p21. To our knowledge, this is the only mutation described in p21. The availability of this mutant p21 should further help in functional studies of p21.
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PMID:A mutant p21 cyclin-dependent kinase inhibitor isolated from a Burkitt's lymphoma. 788 47

Using PCR-SSCP and immunohistochemical analyses, mutations of the p53 tumor suppressor gene were examined in 5 cases of primary malignant lymphoma of the brain (diffuse large cell type). By PCR-SSCP and nucleotide analyses, p53 gene mutations were seen in 2 of the 5 cases. The mutation in one case was a missense G: C-T:A transversion at codon 176 (TGC-TTC; Cys-Phe) which was located in the highly conserved domains and adjoined a previously proposed hot spot codon (codon 175) in various tumors. p53 immunoreactivity was also shown in this case. The mutation in another case was a nonsense G:C-A:T transition at codon 52 (TGG-TGA; Trp-stop codon) leading to a truncated p53 peptide. Thus, these mutations may have actually given rise to serious structural and functional alterations of the p53 protein. These findings suggested that the p53 gene mutation was related with oncogenesis in the primary malignant lymphoma of the brain.
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PMID:Primary malignant lymphoma of the brain: demonstration of the p53 gene mutations by PCR-SSCP analysis and immunohistochemistry. 789 17

Hepatoblastomas generally appear in children aged 2 or 3 years old and arise from apparently normal, non-cirrhotic liver. To elucidate any possible role of p53 mutations in their genesis, we amplified and sequenced exons 5 to 8 of the p53 gene in 10 cases of hepatoblastoma. Somatic mutations were detected in 9 cases, in eight of which a common point mutation at the first-base position of codon 157 was found, resulting in an amino-acid substitution of phenylalanine for valine. Two missense mutations in codon 244, and one each in codons 273 and 279, were also found, with 3 hepatoblastomas having double mis-sense mutations. Out of the total of 12 mutations, 11 were G-to-T transversions. One was a G-to-A transition and guanines were always present on the transcribed strand. Furthermore, p53 over-expression was immunohistochemically observed in 7 out of 9 cases with p53 gene mutations, although the staining pattern was focal and heterogeneous. The findings suggest that particular environmental mutagens may be involved in mutagenesis of the p53 gene in some cases of hepatoblastomas and that p53 mutations at a specific site may play an important role in the genesis of this disease.
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PMID:A mutational hot spot in the p53 gene is associated with hepatoblastomas. 789 46

Infection with hepadnaviruses and exposure to dietary aflatoxin are considered major risk factors in the development of hepatocellular carcinoma (HCC) both in humans and in animals. Recently, a broad range of mutations in the p53 tumor suppressor gene has been reported in human HCCs, predominantly from hepatitis B virus carriers in areas with either high or low levels of exposure to dietary aflatoxin. To determine whether p53 mutations are common to HCCs of hosts infected with related hepadnaviruses with and without treatment with aflatoxin, we studied the occurrence of mutations in the p53 gene in HCCs of ground squirrels and woodchucks with history of infection with ground squirrel hepatitis virus (GSHV) and woodchuck hepatitis virus, respectively. Sequencing of wild type p53 genes from ground squirrels and woodchucks revealed remarkable homology between the two species with only a few amino acid differences in exons 4, 8, and 9. Using direct polymerase chain reaction sequencing, we analyzed the state of the p53 gene (exons 4-9) in 20 HCCs from ground squirrels (2 uninfected, 7 with past, and 11 with ongoing infection with GSHV) and in 11 HCCs from woodchucks persistently infected with woodchuck hepatitis virus. Five GSHV carrier and two uninfected ground squirrels received i.p. administration of aflatoxin B1. We detected only one mutation in the p53 gene of the tested animals. This mutation was located in codon 176 of exon 5 in the HCC of a GSHV-positive ground squirrel treated with aflatoxin. Mutation was caused by a G to T transversion in the second position of the codon, resulting in the replacement of cysteine with phenylalanine, and was accompanied by a tumor-specific loss of heterozygosity. p53 allelic amino acid variation with sequences coding for aspartic acid or asparagine was present in codon 61 in the variable region of exon 4 in both HCCs and nonneoplastic tissues of ground squirrels. In view of the considerably lower apparent rate of mutations in comparison to human HCCs, we suggest a less important role for aflatoxin in the induction of p53 mutations in HCCs of ground squirrels. Alternatively, etiological factors other than p53 mutations may be of greater significance in the development of HCC in ground squirrels and woodchucks.
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PMID:State of the p53 gene in hepatocellular carcinomas of ground squirrels and woodchucks with past and ongoing infection with hepadnaviruses. 792 76

The p53 tumor suppressor gene product is a transcriptional activator that may be associated with its ability to suppress tumor cell growth. The acidic amino terminus of the p53 protein has been shown to contain this trans-activation activity as well as the domains for mdm-2 and adenovirus 5 E1B 55-kD protein binding. An extensive genetic analysis of this amino-terminal p53 domain has been undertaken using site-specific mutagenesis. The results demonstrate that the acidic residues in the amino terminus of p53 may contribute to, but are not critical for, this trans-activation activity. Rather, the hydrophobic amino acid residues Leu-22 and Trp-23 of human p53 are both required for trans-activation activity, binding to the adenovirus E1B 55-kD protein and the human mdm-2-p53 protein in vitro. In addition, hydrophobic residues Leu-14 and Phe-19 are crucial for the interactions between p53 and human mdm-2 (hdm-2). Hydrophobic residues Trp-23 and Pro-27 are also important for binding to the adenovirus 5 (Ad5) E1B 55-kD protein in vitro. These mutations have no impact on the ability of the p53 protein to bind to a p53-specific DNA element. These results suggest that 2-4 critical hydrophobic residues in the amino-terminal domain of the p53 protein interact with the transcriptional machinery of the cell resulting in transcriptional activation. These very same hydrophobic residues contact the hdm-2 and Ad5 E1B 55-kD oncogene products.
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PMID:Several hydrophobic amino acids in the p53 amino-terminal domain are required for transcriptional activation, binding to mdm-2 and the adenovirus 5 E1B 55-kD protein. 792 27


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