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 monoclonal antibody-based antigen capture enzyme-linked immunosorbent assay (ELISA) was developed and employed to detect p24 capsid antigen from human T-cell lymphotropic viruses type I and II (HTLV-I, HTLV-II), simian T-cell lymphotropic virus type I (STLV-I)-infected cell lines, and from mononuclear cell cocultures of HTLV-infected humans and STLV-I infected monkeys. A monoclonal antibody specific for HTLV p24 and p53 capsid antigens was coated onto 96-well microtiter plates to capture HTLV/STLV antigen. Captured antigen was then detected by the addition of a polyclonal, biotinylated human anti-HTLV-I antibody, and color developed with tetramethyl benzidine/H2O2 substrate. As little as 15 pg/ml of HTLV-I p24 antigen could be detected in this assay. Culture supernatants from HTLV-I-infected cell lines (HUT-102, MT-2, C5/MJ, HTLV-II-infected cell lines (Mo-T, Mo-B, PanG 12.1, NRA) and STLV-I-infected cell lines (Matsu, NEPC M39) were all positive in the assay. In addition, p24 was detected from peripheral blood mononuclear cell (PBMC) cocultures of 8 of 8 (100%) HTLV-I diseased patients, 14 of 20 (70%) HTLV-I and HTLV-II-infected, asymptomatic persons, and 8 of 8 (100%) STLV-I-infected, asymptomatic monkeys. Culture supernatants of cells infected with human immunodeficiency virus type (HIV-1), simian immunodeficiency virus (SIV), Chlamydia trachomatis, cytomegalovirus (CMV), herpes simplex I and II (HSV), feline leukemia virus (FELV), bovine leukemia virus (BLV), and bovine immunodeficiency virus (BIV) were all negative. Similarly, normal human peripheral blood mononuclear cells and uninfected, transformed human T cells, were also negative in the assay.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Development of a monoclonal antibody-based p24 capsid antigen detection assay for HTLV-I, HTLV-II, and STLV-I infection. 131 63

To investigate the mechanisms of bovine leukemia virus (BLV)-induced leukemogenesis, we have examined the alterations of the p53 tumor-suppressor gene in sheep and in cattle. The sequences of the open reading frames as well as the intron/exon junctions of the ovine and bovine p53 genes were determined. Pathological samples were screened for the presence of p53 mutations using a single-strand conformational polymorphism assay. Five of ten BLV-induced bovine tumors harbored p53 mutations. In contrast, only one of seven samples corresponding to circulating leukocytes from cattle in persistent lymphocytosis showed an alteration of the p53 gene. Surprisingly, no p53 mutation was found among the 10 BLV-induced sheep tumors analyzed. Altogether, these data indicate that p53 mutations are linked to BLV-induced leukemogenesis in cattle at the transition to the lymphomic stage. These results also enlighten different molecular mechanisms involved in sheep and in cattle during BLV-induced pathogenesis.
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PMID:Mutations in the p53 tumor-suppressor gene are frequently associated with bovine leukemia virus-induced leukemogenesis in cattle but not in sheep. 777 2

Fetal lamb kidney cells (FLK) and bat lung (BAT2CL6) cells that continuously produce bovine leukemia virus (BLV) were found to cause malignant tumors in nude mice. Uninfected bat lung cells (Tb 1 Lu) produced a small benign neoplasm. Pulse chase studies showed that the p53 gene product in BAT2CL6 cells was more stable compared with p53 in Tb 1 Lu cells. Mono-clonal antibody studies suggested that a mutant form of the p53 protein was produced in BLV-infected cells. Heteroduplex mapping studies of the p53 gene from BLV-infected cells also suggested that a mutation in p53 had occurred. Stabilization of the p53 gene product in BLV-infected cells may contribute to the progression of tumor virulence.
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PMID:Stabilization of the p53 gene product in two bovine leukemia virus infected cell lines. 795 52

Bat lung (BAT(2)CL6) cells infected with bovine leukemia virus (BLV) cause malignant tumors in nude mice that after 6 weeks subcutaneous growth, have an average volume of 0.3m(3). Uninfected bat lung cells (Tb 1 Lu) produce small benign neoplasms that average 0.003 cm(3). BAT(2)CL6 cells were transfected in vitro with expression vectors that produce wild type human or mutant p53. Production of human p53 in transfected BAT(2)CL6 cells was confirmed by immunoprecipitation of p53 and by immunohistochemical staining using anti-human p53 monoclonal antibodies. BAT(2)CL6 cells transfected with wild type p53 produced tumors in nude mice averaging 0.03 cm(3) whereas cells transfected with mutant p53 yielded tumors averaging 0.3cm(3). BAT(2)CL6 cell tumors after 1 week subcutaneous growth were transfected in situ with the wild type p53 gene. At 6 weeks tumor volume of in situ transfected tumors was similar to those resulting from cells transfected in vitro. Histopathologic examination and immunochemical staining of tumors produced in nude mice after wild type p53 treatment showed no significant differences when compared to tumors produced by untreated BAT(2)CL6 cells. Therefore, it is likely that the tumors produced by p53 treated-cells arose from cells that escaped transfection. The reduction of tumor size by restoration of wild type 53 may prove to be a useful therapy for BLV-induced tumors.
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PMID:Wild type p53 reduces the size of tumors caused by bovine leukemia virus-infected cells. 862 74

Mutations of p53 in the lymphocytes from peripheral blood and from tumoral lymph nodes in six naturally occurring bovine leukemia virus (BLV)-infected cows were examined. A point mutation of the p53 gene was found in three of six (50%) BLV-infected cows. These p53 gene mutations resulted in amino acid substitutions of codons 144, 167 and 241. The BLV-infected cow in the tumor stage had abnormally proliferating monoclonal B-lymphocytes having the p53 mutation. However, the mutation was not found in somatic cells, except for tumor cells. These results show that p53 mutation plays an important role in the pathogenesis of BLV-induced neoplasms, and that the B-lymphocyte bearing p53 mutations may be a target cell for tumor formation of enzootic bovine leukosis.
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PMID:p53 mutation as a potential cellular factor for tumor development in enzootic bovine leukosis. 915 6

To elucidate the mechanism of leukemogenesis induced by bovine leukemia virus (BLV), the abnormality of p53 tumor suppressor gene was examined using the sequencing method of polymerase chain reaction (PCR)-amplified DNA from peripheral blood lymphocytes (PBL) and tumors from BLV-infected cattle that showed evidence of different stages during the progression of enzootic bovine leukosis (EBL). Mutations of the p53 gene were found in tumor cells from cattle with EBL, but not in PBL from BLV-free normal cattle or BLV-infected cattle without any evidence of tumor, suggesting mutation of p53 gene occurred specifically at the lymphoma stage of the disease. Twelve of eighteen cattle with EBL had seven missense and five silent mutations. The mutations were mapped to the highly evolutionarily conserved regions of p53 gene, and were involved in the DNA binding of p53. Thus, it appeared that the p53 point mutation is one of the critical events leading from the asymptomatic stage to the lymphoma stage.
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PMID:Point mutation of p53 tumor suppressor gene in bovine leukemia virus-induced lymphosarcoma. 920 85

As a cyclin-dependent kinases (Cdks) inhibitor (CDI), the protein p21WAF1/CIP1 is able to interfere with cell cycle progression. Its expression is upregulated by wild-type p53, and the p21WAF1/CIP1 protein appears to be a potent effector of the p53-dependent cell cycle regulatory pathway. We have previously reported that p53 mutations frequently occur during bovine leukemia virus (BLV)-induced leukemogenesis in cattle but not in sheep. Therefore, we have investigated the involvement of p21WAF1/CIP1 mutations in the tumorigenic process associated with BLV. We first cloned the bovine and ovine WAF1 genes and determined the complete nucleotide sequences of their second coding exons. These sequences share respectively 79% and 80% homology with those of the human counterpart exon. In order to screen for mutations that could be associated with BLV-induced pathogenicity, we performed single strand conformation polymorphism (SSCP) assays on the WAF1 genes from BLV-induced tumors. No WAF1 mutations were detected in any of the ten BLV-induced bovine tumor samples. Among eleven sheep tumors and three ovine cell lines, only one sample revealed a single mutation in the WAF1 coding sequence, but this mutation was silent at the translational level. We concluded that mutations of the WAF1 gene are not involved in the development of the tumors during BLV-induced leukemogenesis.
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PMID:Lack of mutation in the WAF1/CIP1 gene during bovine leukemia virus-induced leukemogenesis. 947 80

The mutations of the p53 gene previously represented one of several genetic changes involved in the development of bovine leukemia virus (BLV)-induced lymphosarcoma, while the effects of these mutations on the function of p53 are unknown. We identified four mutations of p53 gene in BLV-infected cattle with lymphosarcoma and demonstrated clearly the existence of two functionally distinct groups of mutants: (i) the mutant forms with substitutions at codons 241 and 242, which were mapped within an evolutionally conserved region and corresponded to the human "hot-spot" mutations, had completely lost the capacities for transactivation and growth suppression and gained transdominant repression activity in p53-null SAOS-2 cells; and (ii) the mutations at codons 206 and 207 were located outside the evolutionally conserved regions. These mutants partially retained the capacity for transactivation and growth suppression and failed to inhibit the transactivation activity of coexpressed wild-type p53, instead showing an enhancement of this activity. In addition, protein analysis using an antibody specific for the mutant form revealed that the mutations at codons 206 and 242 induced a "mutant" conformation of the bovine p53 proteins. Collectively, these results show that mutations of p53 gene in BLV-infected cattle with lymphosarcoma can potentially alter its physiological function and may play an important role in BLV-induced leukemogenesis. Copyright 1998 Academic Press.
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PMID:Function and Conformation of Wild-Type p53 Protein Are Influenced by Mutations in Bovine Leukemia Virus-Induced B-Cell Lymphosarcoma 952 33

The mutations of the p53 gene previously represented one of several genetic changes involved in the development of bovine leukemia virus (BLV)-induced lymphosarcoma, while the effects of these mutations on the function of p53 are unknown. We identified four mutations of p53 gene in BLV-infected cattle with lymphosarcoma and demonstrated clearly the existence of two functionally distinct groups of mutants: (i) the mutant forms with substitutions at codons 241 and 242, which were mapped within an evolutionally conserved region and corresponded to the human "hot-spot" mutations, had completely lost the capacities for transactivation and growth suppression and gained transdominant repression activity in p53-null SAOS-2 cells; and (ii) the mutations at codons 206 and 207 were located outside the evolutionally conserved regions. These mutants partially retained the capacity for transactivation and growth suppression and failed to inhibit the transactivation activity of coexpressed wild-type p53, instead showing an enhancement of this activity. In addition, protein analysis using an antibody specific for the mutant form revealed that the mutations at codons 206 and 242 induced a "mutant" conformation of the bovine p53 proteins. Collectively, these results show that mutations of p53 gene in BLV-infected cattle with lymphosarcoma can potentially alter its physiological function and may play an important role in BLV-induced leukemogenesis.
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PMID:Function and conformation of wild-type p53 protein are influenced by mutations in bovine leukemia virus-induced B-cell lymphosarcoma. 954 Jul 87

Tumor viruses can be found in both the RNA and DNA virus kingdoms. All RNA tumor viruses belong to the retrovirus family. Directly transforming Class I RNA tumor viruses carry cellular oncogenes, picked up by accidental recombination, and usually selected for secondary modifications and high tumorigenicity by the investigator. They are not known to play any role for tumor causation in nature. Class II or chronic RNA tumor viruses do not carry cell-derived oncogenes but they often act by proviral DNA insertion into the immediate neighborhood of a cellular oncogene. Feline, murine, and avian leukemia viruses belong to this category. The human adult T-cell leukemia virus, (HTLV-1) and bovine leukemia virus (BLV) act by expanding the preneoplastic cell population and thereby provides the soil for secondary, cellular changes. The DNA tumor viruses belong to three very different categories, the papovaviruses, adenoviruses and herpesviruses. Inactivation of the Rb and the p53 pathway by the viral transforming proteins is a convergent feature of the papova- and the adenoviruses. Since all DNA tumor viruses kill their host cell following their entry into the lytic phase, transformation and tumorigenicity are entirely dependent on a non-lytic interaction. Cells transformed by DNA tumor viruses depend on the continued expression of the virally encoded oncogene. They provide thereby a convenient target for the immune surveillance of the host. Depending on the epidemiological history of the virus in relation to its natural host species, the immune surveillance of the host and the strategy of viral latency and survival can evolve into a truly symbiotic relationship, as best illustrated by the Epstein-Barr virus (EBV). Tumor development occurs only as an accident at the level of the host (immunosuppression) or the cell (specific translocations or other genetic changes). The list of human viruses presently known to cause or to contribute to tumor development comprise four DNA viruses, namely Epstein-Barr virus, certain human papilloma viruses subtypes, hepatitis B virus, and Kaposi sarcoma herpesvirus (HHV-8); and two RNA viruses, adult T-cell leukemia virus (HTLV-1) and hepatitis virus C.
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PMID:Perspectives in studies of human tumor viruses. 1177


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