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)

A polymerase chain reaction (PCR)-mediated RNase protection analysis was performed to detect subtle genetic alterations of p53 in medullary thyroid carcinoma (MTC) and pheochromocytoma. None of the 30 pheochromocytomas showed abnormal RNase protection patterns. Only one of 32 MTCs showed an abnormal pattern, and subsequent DNA sequencing of the PCR product revealed that it had a G to C transversion in codon 49 that resulted in a change from aspartic acid to histidine. However, this was a sporadic MTC with no specific clinicopathological characteristics. On the basis of a previous report that genes on chromosome 17p were not deleted in MTCs and were relatively infrequently deleted in pheochromocytomas, our results suggest that the p53 gene is not involved in tumorigenesis of MTC or pheochromocytoma.
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PMID:Inactivation of the p53 gene is not required for tumorigenesis of medullary thyroid carcinoma or pheochromocytoma. 148 23

We generated a number of simian virus 40 (SV40) mutants with single amino acid substitutions in T antigen between residues 388 and 411. All but one mutant (398LV) replicated like wild-type SV40 and gave rise to normal-size plaques. Three different mutations at residue 402 (Asp to Glu, Asn, or His) totally prevented the formation of stable complexes with the cellular protein p53 in monkey cells but had no effect on virus replication. Only one other mutation in this region, involving residue 401 (Met to Thr), slightly inhibited the formation of T-monkey p53 complexes. The three mutant T antigens with substitutions at residue 402 also formed no stable complexes with human p53 but generated low levels of complexes with mouse p53. These results indicate that residue 402 is critical for binding to monkey and human p53 proteins and is important for binding to mouse p53. We suggest that it is one of several points of contact. In cells infected with any one of the three residue 402 mutant viruses. T antigen and p53 became increasingly phosphorylated, as they were in cells infected with wild-type virus. Our data therefore show that stable T-p53 complexes are not required for replication of SV40 in culture or for enhanced phosphorylation of either protein.
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PMID:Stable T-p53 complexes are not required for replication of simian virus 40 in culture or for enhanced phosphorylation of T antigen and p53. 170 96

The p53 tumor suppressor gene was examined by direct sequencing of polymerase chain reaction-amplified DNA from fresh tumor cells of 10 patients with adult T-cell leukemia (ATL). Samples included nine patients with acute or lymphomatous ATL, and one patient in whom samples were examined in both his acute and chronic stages of ATL. Four missense mutations and one silent point mutation in the coding region of the p53 gene were found in cells from five patients with either acute or lymphomatous ATL. The missense mutations were homozygous and occurred in evolutionarily highly conserved regions of p53. One patient had no p53 mutation in his leukemic cells during chronic phase of ATL, but had a homozygous point mutation at codon 273 (Arg to His) when he progressed to acute ATL. In summary, we show that p53 is frequently mutated in the acute phase of ATL and one informative case suggests that p53 mutations may be associated with the transition from chronic to acute ATL.
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PMID:Mutations of the p53 gene in adult T-cell leukemia. 173 92

Abnormalities of p53 mRNA in adult T-cell leukemia (ATL) were analyzed using reverse transcription-polymerase chain reaction-single strand conformation polymorphism analysis. Mutations were present in two of 12 ATL patients studied, but not in 3 cell lines immortalized by human T cell leukemia virus type 1 (HTLV-1) infection in vitro. Direct sequencing analysis of the p53 gene from these two patients revealed missense point mutations at codon 153 (arginine to histidine) or codon 220 (cysteine to tyrosine), respectively. Immunohistochemical analysis revealed the elevated expression of p53 proteins in ATL cells from a patient carrying the mutated p53 gene at codon 158. Neither gross rearrangement of p53 gene nor abnormal size of mRNA for the gene was demonstrated by Southern or Northern blot analyses. Thus, there is a mutated p53 in some patients with ATL. The involvement of abnormalities in some suppressor oncogenes may play a role in the development of ATL.
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PMID:Genetic alteration of p53 in some patients with adult T-cell leukemia. 177 65

Simian virus 40 large T antigen contains a single sequence element with an arrangement of cysteines and histidines that is characteristic of a zinc finger motif. The finger region maps from amino acids 302 through 320 and has the sequence C-302 L K C-305 I K K E Q P S H Y K Y H-317 E K H-320. Previous genetic analysis has shown that the cysteine and histidine sequences and the contiguous S H Y K Y region in the finger are important for DNA replication in vivo. We show here that representative mutations in either of these elements of the finger prevent the assembly of large T antigen into stable hexamers in vitro. These same mutations have a characteristic effect on the interaction of T antigen with the simian virus 40 core origin of replication. The mutant T antigens bind to the central pentanucleotide domain of the core origin but fail to melt the adjacent inverted repeat domain and to untwist the adenine-thymine domain. These defects would prevent the formation of a replication bubble and the initiation of DNA replication. Finger mutations have lesser effects on the helicase function of T antigen and no observable effect on binding of T antigen to the mouse p53 protein. We propose that the zinc finger region contributes to protein-protein interactions essential for the assembly of stable T-antigen hexamers at the origin of replication and that hexamers are needed for subsequent alterations in the structure of origin DNA. We cannot exclude the possibility that the zinc finger region also makes specific contacts with components of origin DNA.
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PMID:The zinc finger region of simian virus 40 large T antigen is needed for hexamer assembly and origin melting. 185 75

A putative tumor suppressor gene, p53, has been shown to be altered in a variety of human tumor types. The primary mechanism of p53 inactivation is believed to be mutation of one allele followed by loss of the second allele. Malignant mesothelioma is a tumor that has been highly associated with exposure to asbestos fibers, which are known to cause chromosomal abnormalities in mesothelial cells. We have examined four mesothelioma cell lines for genetic abnormalities in p53. Cytogenetic analysis revealed that two of the four tumors had abnormalities (numerical and/or structural) of chromosome 17 (the locus of the p53 gene). Restriction fragment length polymorphism analysis using a chromosome 17p-specific probe (pYNZ22) revealed that two tumors had loss of heterozygosity in the region of 17p13. The relative level of p53 mRNA expression was examined by Northern analysis, with one tumor showing negligible expression of p53 mRNA. The complementary DNA of p53 was generated from the three tumors showing detectable mRNA expression, and the region between codons 70 and 319 was amplified by the polymerase chain reaction and sequenced. DNA single-base substitutions were detected in two of the tumor cell lines, each resulting in amino acid substitutions. One tumor had an arginine to histidine substitution at position 175, and one tumor had a glycine to aspartic acid substitution at position 245. The observed mutations took place in regions of high cross-species sequence homology, indicating that these regions may be functionally important. The correlation of chromosomal loss in 17p on the cytogenetic and molecular level along with p53 mRNA expression and DNA sequence data indicate that genetic alterations in p53 could be a feature of malignant mesotheliomas and may reveal an important role of asbestos fibers in tumor suppressor gene inactivation.
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PMID:Genetic alterations of the p53 gene are a feature of malignant mesotheliomas. 191 60

The p53 gene has been implicated as a tumour suppressor, with mutations occurring in many carcinomas, such as colon, breast and lung. We have sequenced exons 5, 7 and 8 containing conserved gene regions in the only available differentiated thyroid follicular carcinoma cell line and found a mutation at position 273, Arg----His, with no normal allele present. The same mutation was also present in DNA from the tumour of origin. However immunohistochemical analysis of 129 human thyroid tumours using a panel of p53 antibodies was unequivocally negative. Southern blotting in 20 cases failed to demonstrate any deletion or rearrangement, and direct genomic sequencing of 20 carcinomas showed normal DNA sequence for exons 5, 7 and 8. Thus p53 abnormalities may not be important in human thyroid carcinogenesis, in contrast to colon, breast and lung. However, the FTC 133 cell line was only established after 132 unsuccessful attempts with other differentiated thyroid follicular tumours. Since this line and the corresponding tumour of origin have a p53 mutation, we propose that p53 mutation may confer on thyroid follicular tumour cells the ability to grow in culture. This has potential applications for the future development of thyroid carcinoma cell lines.
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PMID:Mutation of the p53 gene in a differentiated human thyroid carcinoma cell line, but not in primary thyroid tumours. 192 34

Previous studies have demonstrated that allelic deletions of the short arm of chromosome 17 occur in over 75% of colorectal carcinomas. Twenty chromosome 17p markers were used to localize the common region of deletion in these tumors to a region contained within bands 17p12 to 17p13.3. This region contains the gene for the transformation-associated protein p53. Southern and Northern blot hybridization experiments provided no evidence for gross alterations of the p53 gene or surrounding sequences. As a more rigorous test of the possibility that p53 was a target of the deletions, the p53 coding regions from two tumors were analyzed; these two tumors, like most colorectal carcinomas, had allelic deletions of chromosome 17p and expressed considerable amounts of p53 messenger RNA from the remaining allele. The remaining p53 allele was mutated in both tumors, with an alanine substituted for valine at codon 143 of one tumor and a histidine substituted for arginine at codon 175 of the second tumor. Both mutations occurred in a highly conserved region of the p53 gene that was previously found to be mutated in murine p53 oncogenes. The data suggest that p53 gene mutations may be involved in colorectal neoplasia, perhaps through inactivation of a tumor suppressor function of the wild-type p53 gene.
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PMID:Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. 264 81

An autopsy case of HTLV-I associated myelopathy (HAM) was reported. The patient was a 55-year-old man from Kagoshima, who had no history of blood transfusion. He was admitted to our hospital because of muscle weakness of legs and dysuria, which having since one month ago. On admission, he was able to walk with assistance, but his legs were severely spastic, and Babinski's sign was positive bilaterally. Superficial sensation was normal, but vibration sense was mildly decreased in his legs. CSF showed mild mononuclear pleocytosis with elevated protein. Myelogram and CT were normal. Serum and CSF antibodies to HTLV-I were positive at titers of X4,096 and X128, respectively by immunofluorescent assay, and specific IgG bands (p19, p24, p28 and p53 in serum and p19, p24, p53 in CSF) were detected by western blot analysis. His paraparesis continued to worsen. He became bed-ridden within 2 months. He was received corticosteroid medication. He regained the ability to walk with assistance, and continued taking corticosteroid. In July 4, 1986, macrohematuria appeared and inoperable transitional cell carcinoma of rt. kidney was found by further examination. Chemotherapy were not effective against the carcinoma and he died on July 21, 1987. Neuropathological findings were summarized as follows: cerebral hemisphere was normal except for mild cellular infiltration in the leptomeninges; lesions consisted in unilateral pyramidal tract of pons & medulla and in partial anterior, posterior and lateral columns of the spinal cord; demyelination with axonal degeneration, marked gliosis, numerous lipid-laden macrophages and mild perivascular infiltration of mononuclear cells in these areas.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[An autopsy case of HTLV-I associated myelopathy (HAM)]. 275 64

TATA-binding protein (TBP) gene promoter binding factor (TPBF) is a transactivator which binds to the TBP promoter element (TPE) sequence of the Acanthamoeba TBP gene promoter and stimulates transcription in vitro. We have isolated a cDNA clone encoding TPBF. TPBF is a polypeptide of 327 amino acids with a calculated molecular mass of 37 kDa. The predicted amino acid sequence of TPBF shows no significant homology to other proteins. TPBF has two potential coiled-coil regions, a basic region, a proline-rich region, a histidine-rich N terminus, and a nuclear targeting sequence. The recombinant protein has an apparent molecular mass of 50 kDa, identical with that of TPBF purified from Acanthamoeba. Recombinant TPBF is able to bind DNA and activate transcription with the same specificity as natural Acanthamoeba TPBF, demonstrating the authenticity of the clone. Mobility shift assays of co-translated TPBF polypeptides and chemical cross-linking demonstrate that TPBF is tetrameric in solution and when bound to DNA. Analyses of TPBF mutants show that Coiled-coil II is essential for DNA binding, but Coiled-coil I and the basic region are also involved. TPBF is thus a novel DNA-binding protein with functional similarity to the tumor suppressor protein p53.
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PMID:Cloning, expression, and characterization of the TATA-binding protein (TBP) promoter binding factor, a transcription activator of the Acanthamoeba TBP gene. 749 9


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