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

In this study we analyzed the ratp53 promoter by electrophoretic mobility shift assay (EMSA) and DNase I footprinting analysis. As a result we identified two protein binding elements (element 1: -296 to -312, element 2: -195 to -219) with sequence homology to each other. The two identified elements bind to the same kind of protein. To identify the protein binding to these elements, competition assays were carried out with double stranded oligonucleotides containing NF1, YY1, and CRE consensus motifs. Only the NF1 consensus motif competed with element 1 and 2. Element 2 is conserved between the rat, human, and mouse p53 promoters, and has an NF1 consensus motif. However, the sequences of element 1 are comparatively variable between the species. Only the element 1 region of the rat p53 promoter has partial homology to the NF1 consensus motif. This suggests that the element 1 is specific for the rat p53 gene. The molecular mass of the binding protein, determined by Southwestern blotting analysis, was 40 kDa, which is different from that of NF1. In EMSA with an anti-NF1 antibody, DNA-protein complexes were neither supershifted nor decreased. The 40 kDa protein was also detected in rat spleen and lung, but not in kidney. The binding protein was purified by sequence-specific DNA affinity chromatography and it was confirmed that the purified protein binds to the two regions. It was also proved that the identified two elements are required for basal level transcription of the rat p53 gene by in vitro transcription assay.
 ...
PMID:Transcription of the rat p53 gene is mediated by factor binding to two recognition motifs of NF1-like protein. 986 6

Twelve Barrett's adenocarcinomas have been analysed for the occurrence of allelic imbalance (LOH) on chromosome 17 using 41 microsatellite markers. This study provides evidence for 13 minimal regions of LOH, six on 17p and seven on 17q. Four of these centre in the vicinity of the known tumour suppressor genes (TSGs) TP53 (17p13.1), NFI (17q11.2), BRCA1 (17q21.1), and a putative TSG (17p13.3). The tumours all displayed relatively small regions of LOH (1-10 cM), and in several tumours extensive regions of LOH were detected. One tumour displayed only two very small regions of LOH; 17p11.2 and 17p13.1. The frequency of allelic imbalance has been calculated based on the LOH encompassing only one minimal region, and based on all the LOH observations. By both evaluations the highest LOH frequencies were found for regions II (p53), III (17p13.1 centromeric to p53), IV (17p12), V (17p11.2) and VII (NF1, 17q11.2). Our data supports the existence of multiple TSGs on chromosome 17 and challenges the view that p53 is the sole target of LOH on 17p in Barrett's adenocarcinoma.
 ...
PMID:Multiple target sites of allelic imbalance on chromosome 17 in Barrett's oesophageal cancer. 1002 74

The NF1 gene product (neurofibromin) is known to act as a tumor suppressor protein by inactivating ras. The best documented factors involved in urinary bladder transitional cell carcinoma (TCC) are ras proto-oncogene activation and p53 suppressor gene mutations. This is the first study reporting alterations in NF1 gene expression in TCC. We examined NF1 gene expression in a total of 29 surgical urinary bladder TCC specimens representing grades 1 to 3 and in three cell lines, RT4, 5637, and T24 (representing grades 1 to 3, respectively). Decreased NF1 gene expression was observed in 23 of 29 (83%) TCC specimens as estimated by immunohistochemistry, the decrease being more pronounced in high-grade tumors. NF1 mRNA levels were markedly lower in TCC tissue compared with adjacent non-neoplastic urothelium, as studied by in situ hybridization for grade 3 TCC. Immunohistochemistry and Western blotting demonstrated that TCC cell lines expressed NF1 protein at different levels, expression being almost undetectable in T24 (grade 3) cells. Northern blotting for cell lines demonstrated reduced NF1 mRNA levels in grade 3 TCC cells. Reverse transcription polymerase chain reaction for cell lines and selected grade 2 and grade 3 tissue samples demonstrated NF1 type II mRNA isoform predominance in all samples studied. Our results show that both NF1 mRNA and protein levels are decreased in high-grade TCC, suggesting that alterations of NF1 gene expression may be involved in bladder TCC carcinogenesis.
 ...
PMID:Urinary bladder transitional cell carcinogenesis is associated with down-regulation of NF1 tumor suppressor gene in vivo and in vitro. 1007 53

The rat p53 promoter has several potential transcription factor-recognition motifs. They include NF1-like, bHLH family, and AP1-like proteins binding sites. The binding protein to NF1-like motif was previously identified. The protein has about 40kDa of molecular mass, which is smaller than that of NF1. Anti-NF1 polyclonal antibody does not recognize the protein. In this study, we isolated the 40kDa protein by sequence-specific DNA affinity chromatography. The isolated protein was assayed by DNase I footprinting analysis. To determine the transactivation effect of the protein, in vitro transcription with the purified 40kDa protein was carried out. After the addition of the purified 40kDa protein into the transcription reaction mixture, the transcription level of the p53 promoter was increased. This suggests that the 40 kDa NF1-like protein is a transcription activator for the rat p53 gene.
 ...
PMID:In vitro transcription assay with the purified 40kDa NF1-like protein binding to the rat p53 promoter. 1020 79

Six expressed gene loci (NF1, CRYB1, CHRNB1, TP53, P4HB and GH1), recently assigned to cattle chromosome 19 by both radiation hybrid analysis and FISH-mapping, were comparatively FISH-mapped to river buffalo chromosome (BBU) 3p and sheep chromosome (OAR) 11, extending the physical map in these two important bovids. The six loci mapped to the same homoeologous chromosome bands of BBU 3p and OAR 11, and their gene order was centromere-NF1-CRYB1-CHNRB1-TP53-(GH1, P4HB).
 ...
PMID:Comparative FISH-mapping of six expressed gene loci to river buffalo and sheep chromosomes. 1039 19

Two recognition motifs of a 40-kDa NF1-like protein were previously identified in the rat p53 promoter. One is located between -296 and -312 (NF1-like element 1) and the other between -195 and -219 (NF1-like element 2). The latter one was also identified as a NF1/YY1 recognition motif in the human p53 promoter. NF1 or YY1 binds to the motif and regulates the expression of the human p53 gene in a tissue-specific manner. In this study, we investigated the binding protein for NF1-like element 2 in various rat tissues. Unlike the human p53 transcription, an NF1-like protein, not YY1, bound to the motif in every tested tissue: thymus, kidney, and spleen. In vitro transcription assay also confirmed that the NF1-like protein regulated the p53 transcription in rat spleen, although the human p53 transcription was regulated by YY1 in that organ. The molecular mass of the binding protein was determined to be 40 kDa, which was the same as that of the NF1-like protein identified in liver. Therefore, the 40-kDa NF1-like protein may be a universal transcription regulator for the rat p53 gene.
 ...
PMID:A 40-kDa NF1-like protein, not YY1, binds to the rat p53 promoter for transactivation in various rat organs. 1050 91

Different transcription factors activate and repress the p53 gene expression. Recently, a tissue specific binding of NF1/YY1 to p53 promoter has been reported and further, it has been demonstrated that NF1/YY1 activates p53 promoter activity. The deregulated expression of p53 appears to be a central feature of malignant transformation and the basis of this deregulation is not well defined. Hence, an attempt has been made to know the binding of NF1/YY1 to p53 promoter taking breast tumour as a model system. Results have indicated a differential binding of NF1 to p53 promoter and a depletion or low level of NF1 in majority of breast tumour samples. Further, a correlation between NF1 and p53 has indicated the presence of p53 RNA even without NF1. Hence it is assumed that p53 expression is not NF1-dependent in breast tumours. However, the results clearly demonstrate a deregulation of NF1 transcription factor in breast tumours.
 ...
PMID:Differential binding of NF1 transcription factor to P53 gene promoter and its depletion in human breast tumours. 1063 4

Superficial transitional cell carcinomas (TCC) of the urinary bladder have been shown to be monoclonal. However, no combined study of clonality and tumor suppressor genes (TSG) is available to date for muscle-invasive TCC. Forty-four muscle-invasive TCC of the urinary bladder selected from women were included in this study. Tumor cells located above and below the muscularis mucosa zone were systematically microdissected and used for DNA extraction. Hha-I digested and undigested samples were used to study the methylation pattern of androgen receptor alleles and undigested samples were used for microsatellite analysis of TSG (TP53, RB1, WT1, and NF1). Both loss of heterozygosity (LOH) and single nucleotide polymorphism (SNP) analyses were performed using optimized denaturing gradient gel electrophoresis. The expression of p53, pRB, and p21WAF1 was assessed by immunohistochemistry. Appropriate controls were run in every case. All except two TCC showed a monoclonal pattern with the same allele inactivated in both compartments. Microsatellite analysis of TSG revealed the same LOH/SNP pattern in both tumor compartments in 30 cases (involving more than 1 TSG locus in 8) and genetic heterogeneity in 14 cases. From the latter group, 9 cases expressed more genetic changes in the deep compartment (involving TP53 gene in all cases, WT1 gene in 2, and NF1 in 1), whereas in 4 cases the superficial compartment showed more genetic changes (three involving NF1 and one involving both RB and TP53). No statistical difference in the immunoexpression was detected, although it tended to be higher in the superficial compartment than in the deep compartment. These concordant data in polymorphic DNA regions indicate that bladder-muscle-invasive TCC are monoclonal proliferations with homogeneous tumor cell selection. Heterogeneous tumor cell selection by topography defined two different genetic compartments: superficial, NF1-defective, and deep, TP53-defective. No differences in the immunohistochemical expression were observed, precluding a more extensive clinical application.
 ...
PMID:Molecular evolution and intratumor heterogeneity by topographic compartments in muscle-invasive transitional cell carcinoma of the urinary bladder. 1074 64

We previously reported that two nuclear factor 1-like elements mediated the transcription of the rat p53 gene. A 40-kDa protein was shown to bind to these elements, which was different from common NF1 family proteins. In this study, the biochemical properties of the 40-kDa binding protein were investigated. The metal ion dependency of the protein was examined with various chelators; the protein was proved to require Mg(2+) for maximum DNA-binding activity. The binding protein was highly resistant to ionic strength and denaturant. The protein-DNA complex was reduced at high NaCl concentration, but residual DNA-binding activity remained. Even 2 M urea did not completely eliminate the formation of protein-DNA complex. DNA-binding activity of the protein was also stable at high temperature. Treatment of the protein-DNA complex with increasing concentrations of proteinase K or trypsin demonstrated the existence of a protease-resistant DNA-bound core. These biochemical properties provide new insight into the 40-kDa NF1-like nuclear factor.
 ...
PMID:Biochemical characterization of a nuclear factor that binds to NF1-like elements in the rat p53 promoter. 1079 61

C-cell hyperplasias are normally multifocal in multiple endocrine neoplasia type 2A. We compared clonality, microsatellite pattern of tumor suppressor genes, and cellular kinetics of C-cell hyperplasia foci in each thyroid lobe. We selected 11 females from multiple endocrine neoplasia type 2A kindred treated with thyroidectomy due to hypercalcitoninemia. C-cell hyperplasia foci were microdissected for DNA extraction to analyze the methylation pattern of androgen receptor alleles and microsatellite regions (TP53, RB1, WT1, and NF1). Consecutive sections were selected for MIB-1, pRB1, p53, Mdm-2, and p21WAF1 immunostaining, DNA content analysis, and in situ end labeling. Appropriate tissue controls were run. Only two patients had medullary thyroid carcinoma foci. Nine informative C-cell hyperplasia patients showed germline point mutation in RET, eight of them with the same androgen receptor allele preferentially methylated in both lobes. C-cell hyperplasia foci showed heterogeneous DNA deletions revealed by loss of heterozygosity of TP53 (12 of 20), RB1 (6 of 14), and WT1 (4 of 20) and hypodiploid G0/G1 cells (14 of 20), low cellular turnover (MIB-1 index 4.5%, in situ end labeling index 0.03%), and significantly high nuclear area to DNA index ratio. MEN 2A (germline point mutation in RET codon 634) C-cell hyperplasias are monoclonal and genetically heterogeneous and show down-regulated apoptosis, findings consistent with an intraepithelial neoplasia. Concordant X-chromosome inactivation and interstitial gene deletions suggest clone expansions of precursors occurring at a point in embryonic development before divergence of each thyroid lobe and may represent a paradigm for other germline mutations.
 ...
PMID:Germline RET 634 mutation positive MEN 2A-related C-cell hyperplasias have genetic features consistent with intraepithelial neoplasia. 1150 37


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>