Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A novel gene, termed p73, encodes a protein with a significant homology to p53 and has been mapped at chromosome 1p36.3, which is a locus of multiple suppressor genes for tumors including neuroblastoma and other cancers. Since the 1p36 locus is reported to be deleted and p53 is frequently mutated in esophageal carcinomas, we examined loss of heterozygosity (LOH) and mutation of the p73 gene in 48 untreated esophageal tumors, as well as mRNA expression in 8 tumors. We screened the P1 genomic library to obtain a P1 clone containing the p73 gene and found a polymorphic short tandem CT repeat site at intron 9. Intragenic sequences for 14 PCR primer sets and a primer pair flanking the repeat were also determined for the analysis of PCR single-strand conformation polymorphism (SSCP) and LOH studies, respectively. Expression of p73 mRNA was detectable but at low levels in all 8 tumor tissues by reverse transcriptase PCR. We did not find any type of mutation other than polymorphisms in the 48 esophageal carcinomas, though aberration of the p53 gene on the PCR-SSCP gels was observed in 15 of 38 (39%) tumors of the same set. In addition, LOH for p73 was found in only 2 of 25 (8%) tumors. These results suggest that, at least in esophageal carcinomas, allelic loss or mutation of p73 may not be a main genetic event for the tumorigenesis as it is with p53.
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PMID:p73, a gene related to p53, is not mutated in esophageal carcinomas. 979 31

Recently p73, a novel p53 homologous tumour suppressor gene, has been cloned and mapped to chromosome 1p36. Like p53, important functions of p73 in controlling the cell cycle and programmed cell death have been described. Loss of p73 has been demonstrated in neuroblastomas and its involvement in tumorigenesis has been suggested to occur in other neuroectodermal cancers. Since genetic alterations at the tumour suppressor locus 1p36 have been also identified in malignant melanomas, we investigated the expression of p73 in a panel of nine different human melanoma cell lines, 17 melanocytic naevi, 17 primary malignant melanomas and 20 metastases by reverse transcriptase polymerase chain reaction (PCR) and Southern blotting. We observed significant p73 mRNA expression in all the cell lines and tissue specimens except one benign melanocytic naevus and one melanoma metastasis. Sequencing the PCR fragments of nine melanoma cell lines derived from primary tumours and five metastases over the entire p73 DNA binding domain revealed wild-type sequences in all cases. In summary, we conclude that loss of p73 mRNA expression or mutations in the p73 DNA binding domain do not represent common genetic events involved in the pathogenesis of malignant melanomas.
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PMID:Loss of expression or mutations in the p73 tumour suppressor gene are not involved in the pathogenesis of malignant melanomas. 991 12

The p73 gene is a candidate tumor suppressor gene that has significant homology to p53. Thus far, p73 has not been investigated in hematopoietic malignancies. We used single-strand conformation polymorphism analysis to examine 60 de novo acute myelogenous leukemia (AML) patients for p73 mutations in exons 4, 6 and 7, which are homologous to the most frequently mutated exons in p53. Mutations were not found, but we did identify polymorphisms in exons 4 and 7. We also examined p73 RNA expression in 15 AML samples, eight cell lines, and eight normal bone marrows using the reverse transcriptase/polymerase chain reaction assay. All 31 RNA samples had p73 expression. Fourteen RNA samples were informative for allelic expression, being heterozygous for a polymorphism in codon 173 of exon 4. The two normal bone marrows and the K562 cell line had evidence of biallelic expression while six of 10 AML patients and the Kasumi (AML) cell line had monoallelic expression. These data suggest that functional p73 mutations in exons 4, 6 and 7 do not occur in most de novo AML patients. In addition, biallelic expression of p73 occurs in normal bone marrows, some AML samples, and specific cell lines. Lastly, monoallelic p73 expression appears to be common in de novo AML.
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PMID:p73 mutations and expression in adult de novo acute myelogenous leukemia. 1040 Apr 12

The p73 gene, a member of the p53 family, is a new candidate tumor suppressor gene. To investigate the possibility of genetic alteration of p73 in leukemia and lymphoma, we examined 55 cell lines and 39 patient samples together with 17 nonhematopoietic cancer cell lines. Gene expression of p73 was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in cell lines (5 of 7 pre B/B-acute lymphoblastic leukemia [ALL], 13 of 21 T-ALL/lymphoblastic lymphomas [LBL], 9 of 10 B-non-Hodgkin's lymphomas [B-NHL], 8 of 9 acute myelogenous leukemias [AML], 2 of 2 T-NHL, 3 of 3 multiple myeloma), and in patient samples (16 of 23 pre B-ALL, 5 of 8 T-ALL/LBL, 5 of 8 B-NHL). PCR-single-strand conformation polymorphism (SSCP) of cDNAs showed no mutation in 43 p73-expressing cell lines within the regions that corresponded to the 5 mutational hotspots of the p53 gene. Neither homologous deletion nor rearrangement of the p73 gene were found by Southern blot analysis in any of the cell lines that lack expression of p73. In contrast to prior published data, analysis of a polymorphic site showed that the p73 gene was expressed biallelically in cell lines and normal peripheral blood. Notably, the p73-negative cell lines were hypermethylated at a CpG island in the 5' untranslated region of the p73 mRNA, and treatment of these cell lines with 5-azacytidine (5-AC), a demethylation reagent, induced p73 expression. Taken together, we found that a sizable proportion (32%) of ALL/B-NHL cell lines and primary tumors had negligible or limited expression of the p73 gene associated with hypermethylation of the gene. These findings suggest that silencing of the p73 gene by hypermethylation may contribute to development and/or progression of lymphoid neoplasms.
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PMID:Loss of p73 gene expression in leukemias/lymphomas due to hypermethylation. 1041 5

Genetic mutation of p53, which monitors DNA damage and operates cellular checkpoints, is a major factor in the development of human malignancies. A novel gene p63/p73L/p51, encoding a protein with significant homology to p53 and p73, was recently identified at 3q27-9. To investigate the penetration of p63 in cervical carcinogenesis, mutation and transcription analyses of p63 were performed in cervical carcinoma. A certain isotype of p63 called TAp63gamma encodes the acidic N-terminus and possesses a short C-terminus. Using reverse transcriptase-polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) analysis for TAp63gamma, one mutation was found in the cervical carcinoma cell line SKG-I. However, no mutations causing amino acid substitutions or frameshifts were found in 54 cases examined for TAp63gamma, which is thought to be a tumor suppressor gene. While cervical carcinomas tended to yield a positive signal in the RT-PCR reaction designed to amplify transcripts encoding the acidic N-terminus, normal cervix and cervical intraepithelial neoplasia (CIN) did not express this transcript. These data suggest that the p63 gene does not play an essential role as a tumor suppressor gene, but expression of TAp63gamma may be speculatively associated with tumor growth in cervical carcinogenesis.
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PMID:Mutation and transcription analyses of the p63 gene in cervical carcinoma. 1056 21

The p53-related genes, p51/p63 and p73, have been isolated respectively from cDNA libraries of skeletal muscle and the brain, and their structural features and biological functions have been compared. High expression of p51A (TAp63gamma) in the skeletal muscle tissue drove us to investigate a differentiation-inducible myoblastic cell line which showed increased p51A expression after differentiation induction. Tissue-specific expression was further confirmed by reverse transcriptase-polymerase chain reaction (RT - PCR) using primers specific for DeltaN (TA-domain lacking p51), p51A, and p51B expression. p51A alone induced erythrodifferentiation when expressed in the erythroleukemia line (Tg-gp55-1-2-3) expressing a temperature-sensitive mutant of p53, and induced remarkable apoptosis when wild-type p53 expression was induced by the temperature shift to 32 degrees C. Human p51A and p53 were introduced exogenously into the above erythroleukemia cells, and although their expression was rather low, both p51A and p53 proteins were induced by DNA-damaging treatment with UV and ActinomycinD. However, the protein-protein interactions analyzed by a yeast two-hybrid assay between p51 and p53, between p51 and p73, and between p51 and oncoproteins showed that p51 is functionally rather distant from p53. Extensive mutation analysis of p51/p63 in human tumors revealed only four mutations in 80 non-small cell lung carcinomas; two adenocarcinoma cases possessing Glu31His mutations in the transactivation domain (TA) domain, suggesting that p51/p63 is not a Knudson type tumor suppressor gene. Mutation and loss of heterozygosity (LOH) of p73, deregulated expression of p73 and loss of imprinting of p73 are also discussed.
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PMID:p53 family genes: structural comparison, expression and mutation. 1063 27

The expression of the p73 gene and the methylation status was examined in 61 acute lymphoblastic leukemia (ALL) cell lines and lymphocytes from seven healthy individuals. p73 mRNA was not expressed in 19 (31.1%) of 61 ALL cell lines, including 11 (31.4%) of 35 B-precursor ALL cell lines, 2 (16.7%) of 12 B-ALL/Burkitt lymphoma (BL) cell lines (totally 27.7% of B-lineage cell lines), 6 (42.9%) of 14 T-ALL cell lines, and expressed in all of normal lymphocytes, by reverse transcriptase-polymerase chain reaction (RT-PCR). Restriction-enzyme related PCR (REP) and methylation-specific PCR (MSP) revealed that the cell lines lacking p73 mRNA expression were hypermethylated. In contrast, normal lymphocytes and most cell lines that expressed detectable p73 mRNA were not hypermethylated with the exception of five cell lines. Furthermore, bisulfite genomic sequencing confirmed the results obtained by REP and MSP. Our results suggest that p73 inactivation may be involved in the pathogenesis of both T- and B-ALLs, and that hypermethylation is the predominant mechanism of inactivation of the p73 gene in ALL.
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PMID:Loss of p73 gene expression in lymphoid leukemia cell lines is associated with hypermethylation. 1133 15

p63, a member of the p53 gene family, encodes multiple proteins that may either transactivate p53 responsive genes (TAp63) or act as a dominant-negative factor toward p53 and p73 (Delta Np63). p63 is expressed in many epithelial compartments and p63(-/-) mice fail to develop skin, prostate, and mammary glands among other defects. It has been previously shown that p63 is expressed in normal urothelium. This study reports that p63 is regulated in bladder carcinogenesis and that p63 expression is lost in most invasive cancers whereas papillary superficial tumors maintain p63 expression. Examination of bladder carcinoma cell lines reveals that certain lines derived from invasive carcinomas maintain expression of Delta Np63, as demonstrated by both immunoblotting and confirmed by isoform-specific quantitative reverse transcriptase-polymerase chain reaction. Another novel finding reported in this study is the fact that p63(-/-) mice develop a bladder mucosa epithelial layer yet fail to complete uroepithelial differentiation, producing a nontransitional default cuboidal epithelium. These data indicate that in contrast to the skin and prostate, p63 is not required for formation of a bladder epithelium but is indispensable for the specific differentiation of a transitional urothelium.
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PMID:Loss of p63 expression is associated with tumor progression in bladder cancer. 1236 93

p73 is one of the family proteins that share structural and functional homologies with the tumor suppressor p53. To analyze the status of p73 in hepatocellular carcinoma (HCC), the allelic loss, allelic expression, mutation and methylation status of the p73 gene were examined in 18 paired HCC and normal tissues. No allelic loss was found. All heterozygous individuals contained RNA of both alleles, indicating that p73 was biallelically expressed in the liver. Notably, semiquantitative reverse transcriptase polymerase chain reaction analysis showed that p73 was consistently overexpressed in the cancerous tissues. Single-stranded conformation polymorphism and sequencing analysis revealed several polymorphisms, but no mutations were found in the entire coding sequence. Finally, the methylation patterns in the promoter and exon 1 regions of p73 were not altered in the cancerous tissues. These results do not support p73 as a tumor suppressor in HCC, but suggest that overexpression of p73 may in some way be associated with the pathogenesis of HCC.
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PMID:Overexpression but lack of mutation and methylation of p73 in hepatocellular carcinoma. 1254 28

The tenascin-R (TN-R) gene encodes a multidomain extracellular matrix glycoprotein belonging to the tenascin family. It is detectable mainly in oligodendrocytes and neuronal subpopulations of the central nervous system. In this report, we describe the structure of the 5'-region of the mouse TN-R gene and characterise the activity of its promoter. By in silico cloning and genome walking, we have deduced the organisation of the gene and identified the promoter sequence by 5'-RACE technology. TN-R transcripts in adult mouse brain contain non-coding exons 1 and 2 as demonstrated by the reverse transcriptase-polymerase chain reaction. The promoter displays its activity in cultured cells of neural origin, but not in a fibroblast-like cell line or an undifferentiated teratocarcimoma cell line. As for the human and rat genes, the elements required for the full and cell type-specific activity of the promoter are contained in exon 1 and 167 bp upstream of this exon. The mouse TN-R promoter sequence is similar to that of rat and human in that it displays similarly unusual features: it lacks any classical TATA-box or CAAT-box, GC-rich regions or initiator elements. The promoter contains consensus sequences for binding of a variety of transcription factors, notably p53/p73 and glucocorticoid receptors.
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PMID:Structure of the murine tenascin-R gene and functional characterisation of the promoter. 1292 10


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