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)

Abdominal diffuse malignant mesotheliomas develop in rats administered asbestos by the intraperitoneal route. A latency period of 6 to 24 months precedes tumor development; the biological and morphological features of these tumors resemble mesotheliomas in humans. Using one- and two-dimensional gel electrophoresis and immunoblotting, rat mesotheliomas (n = 24) were shown to express two classes of intermediate filament (IF) proteins. The tumors contained both vimentin and at least one of six keratins (p40, Mr 40,000; Dm, Mr 50,000; p53, Mr 53,000; Bm, Mr 53,000; Cm, Mr 54,000; Am, Mr 54,000). Vimentin predominated in 15 of 16 tumors exhibiting either sarcomatous or mixed (epithelial and mesenchymal) appearance. One of eight mixed lesions and six of eight epithelial tumors had a complement of IF proteins in which cytokeratins predominated. A similar pattern has been reported in mesotheliomas in humans (Blobel et al., Am. J. Pathol. 121: 235, 1985). Epithelial tumors often contain comparable amounts of vimentin and low molecular weight cytokeratins, while vimentin is the most actively expressed IF protein in sarcomatous tumors. Thus, tumors induced by asbestos in the rat peritoneum express IF proteins in a manner that resembles human mesotheliomas, supporting the notion that these lesions are appropriate models of human mesothelioma.
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PMID:Intermediate filament proteins in asbestos-induced mesotheliomas of the rat. 244 39

Eighty monoclonal antibodies (MAbs) against parainfluenza virus type 4(PIV-4) were isolated and characterized. Of 50 MAbs against PIV-4A, 14 reacted with the nucleocapsid (NP) protein, 11 with the hemagglutinin-neuraminidase (HN) glycoprotein, 6 with the fusion (F) glycoprotein, and 19 with the matrix (M) protein. With the aid of the PIV-4A and PIV-2 specific MAbs showing cross-reactivity with PIV-4B, the structural proteins of PIV-4B were identified. gp72, p65, gp65, gp55, p53, and p40 of PIV-4B were assigned to HN, NP, Fo, F1, P, and M proteins, respectively. Based on the results, specificities of the MAbs against PIV-4B were determined. Of 30 hybridoma clones against PIV-4B, 13 clones were found to produce antibodies against the NP protein, 7 against the HN protein, and 10 against the F protein. Epitope mapping of these MAbs was performed with competitive binding assays in ELISA. According to their biological activities, the MAbs against the HN protein of either PIV-4A or 4B could be divided into three groups. The first group showed high hemagglutination inhibition (HI), hemolysis inhibition (HLI), and neutralizing (NT) activities. The second group showed high NT activity, but could not block hemagglutination. The final group showed a lower level of all activities. The MAbs against the F protein of PIV-4A and against PIV-4B were divided into two groups. Some MAbs against the F protein had high titer of NT, suggesting that the F protein had neutralizing-related epitopes. Antigenicity of the NP protein was highly conserved among subtypes of PIV-4. On the other hand, the MAbs against the HN and the F proteins showed high reactivity with the homologous subtype viruses, but low reactivity with the heterologous subtype viruses, indicating that the external glycoproteins exhibited antigenic variations between two subtypes of PIV-4. When the immunological interrelationship among various paramyxoviruses was analyzed. PIV-4 was found to be antigenically related to PIV-2, SV 5, and mumps virus.
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PMID:Isolation and characterization of monoclonal antibodies to human parainfluenza virus type 4 and their use in revealing antigenic relation between subtypes 4A and 4B. 247 3

Sera and cerebrospinal fluid (CSF) from patients with human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy (HAM) were analyzed by Western blotting, and normal human leukocytes were transformed by co-cultivation with HAM patients' leukocytes. The sera and CSF from all HAM patients formed specific bands with HTLV-1 viral proteins, including p19, p24, p28, p32, p40 and p53. After 2-3 weeks of co-cultivation, scattered foci of cell aggregates were noted on macrophage sheets. Surface markers of the transformed cells were OKT3(+), OKT4(+), OKT8(-), IL-2 receptor(+) and EBNA(-). Chromosome analysis showed a normal karyotype. HTLV-1 viral genome was integrated into DNA isolated from transformed cell lines. Electron microscopy revealed type C virus particles in transformed T-cell lines. These results indicate that peripheral leukocytes from HAM patients can transform HTLV-1-negative leukocytes and HAM patients have the potential to acquire adult T-cell leukemia in the future.
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PMID:Transformation of human leukocytes by co-cultivation with HTLV-1-associated myelopathy patients' leukocytes. 288 13

A rabbit antiserum (A2) directed against the detergent-solubilized fraction of the simian virus 40-transformed mouse embryo fibroblast cell line VLM detects common antigens in primary cell cultures from BALB/c mouse embryos and in transformed cell lines from various species. Positively reacting cell cultures show a set of polypeptides with molecular weight species p86, p74, p68, p46, p42, p40, and p35. As tested by Western blotting procedures, all immunoprecipitated proteins carry immunologically reactive determinants. By analysis with two-dimensional gel electrophoresis, all precipitated polypeptides show charge heterogeneities. Concerning the two major members of the protein set, p40 consists of at least four subspecies with isoelectric points in the range of pH 6.2-6.8, whereas p35 is composed of two subspecies focusing between pH 6.4 and pH 7.2. By comparison of the two-dimensional patterns of p35 of various transformed cell lines, a basic (pH 6.6-7.2) and an acidic (6.4-6.6) charge type of p35 could be observed. Comparative analyses of primary cell cultures from 12-16-day mouse embryos show the immunoprecipitated set of polypeptides only in the 16-day embryo cell cultures. After six further propagations, these cells express the immunoreactive proteins as strongly as the primary cell cultures. In embryonic cell cultures of day 14 of gestation the expression of this set of antigens is induced only when cells are propagated at least six times. Under identical conditions these proteins could not be induced in cell cultures of 18-day-old mouse embryos. None of the polypeptides could be immunoprecipitated from primary mouse kidney cell cultures of 12-day-old mice even when the cultures were propagated at least 15 times. This set of polypeptides is also present in simian virus 40-transformed cells of hamster, rat, monkey, and human origin. These findings suggest that in simian virus 40-transformed mouse cells, in addition to p53, the synthesis of other embryonic antigens is reactivated. The presence of the described set of polypeptides in polyoma virus-transformed cells of rat and mouse origin and in cell lines derived from malignant human tumors might indicate common functions in metabolic patterns of transformed cells.
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PMID:A set of stage-dependent embryonic antigens expressed in cell cultures of BALB/c mouse embryos and in transformed cell lines. 301 8

The v-Rel oncoprotein of the avian Rev-T retrovirus malignantly transforms chicken spleen cells in vivo and in vitro. We previously described two temperature-sensitive (ts) mutants of v-Rel (v-G37E and v-R273H) that show a ts ability to transform chicken spleen cells and to bind to DNA in vitro. We now show that spleen cell lines transformed by ts v-Rel proteins at the permissive temperature undergo apoptosis when cells are shifted to the nonpermissive temperature. The levels of most proteins (including v-Rel, p53, c-Myc, Rb and Bcl-2) do not change in these cells even at advanced stages of apoptosis. However, the chicken I kappa B-alpha protein (also called p40), which is in a complex with v-Rel in transformed cells, is degraded when ts v-Rel-transformed cells are shifted to the nonpermissive temperature. In v-R273H-transformed cells, p40 is degraded without the appearance of proteolytic intermediates. In contrast, in v-G37E-transformed cells, p40 is cleaved to an intermediate species that is missing approximately 3-4 kDa from its amino terminus. This truncated form of p40 is found in a detergent-insoluble fraction and can also be detected in wild-type v-Rel-transformed cells that are induced to undergo apoptosis by treatment with cycloheximide. Both ts v-Rel proteins are ts for interaction with p40 in vitro. The results reported here indicate that v-Rel blocks a normal pathway of programmed cell death and that I kappa B-alpha can undergo multiple degradative pathways, which can be induced by alterations in the structure of the Rel protein to which it is bound.
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PMID:The v-Rel oncoprotein blocks apoptosis and proteolysis of I kappa B-alpha in transformed chicken spleen cells. 789 28

p53 is able to recognize and bind sites of DNA damage and, in some way, damage to cellular DNA activates a p53 response leading to G1 arrest or apoptosis. We have previously shown that 'damaged DNA' induces N-terminal cleavage of p53 to generate p40(DeltaN) and p35 (core) protein products. We now show that the p35 product has protease activity and is able to cleave between residues 23 and 24 of full-length p53 to generate a novel product, p50(DeltaN23). This activity was inhibited by bestatin, an aminopeptidase inhibitor. Residues 23 and 24 lie within the mdm-2 binding domain of p53 and the possibility that p50(DeltaN23) may be resistant to feedback regulation by mdm-2 is discussed. Unexpectedly, interaction with ssDNA induced two further cleavage products of p53, generated by C-terminal cleavage and designated p50(DeltaC) and p40(DeltaC). In vivo generation of a C-terminal cleavage product of endogenous p53 similar in size to p50(DeltaC) correlated with up-regulation of p21 expression in ML-1 cells exposed to either adriamycin or cisplatin. The possible significance of the various p53 cleavage products in relation to the cellular response to DNA damage is discussed.
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PMID:Induced N- and C-terminal cleavage of p53: a core fragment of p53, generated by interaction with damaged DNA, promotes cleavage of the N-terminus of full-length p53, whereas ssDNA induces C-terminal cleavage of p53. 931 58

Perturbation of p53 protein function is a common, if not universal, finding in human cancer. Tumor suppression by p53 is due, at least in part, to its ability to activate transcription of certain genes involved in cell cycle control and apoptosis (programmed cell death). Two additional members of the mammalian p53 family, p73 and p51, which is also known as p40, p63, KET, or p73L, were recently identified. Both of these proteins share substantial sequence homology with p53 and can, at least when overproduced, activate p53-responsive promoters and induce apoptosis. Nonetheless, data on differences between these proteins and p53 are emerging. For example, p73 is not induced by DNA damage and is not targeted for inactivation by viral oncoproteins such as simian virus 40 (SV40) T antigen, adenovirus E1B 55K, and human papillomavirus E6. In contrast to p53, neither p73 nor p51 appears to be frequently mutated in human cancers on the basis of the limited studies reported to date. Finally, unlike p53, cells produce multiple p73 and p51 isoforms as a result of alternative splicing, and production of p73 and p51 appears to be restricted to certain tissues. Additional studies are required to determine the role, if any, that p73 and p51 play in cell growth control and carcinogenesis.
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PMID:The emerging p53 gene family. 1020 77

After the identification of p73, a second homologue of the human p53 tumor suppressor gene has been reported and named p63/p73L/p51/p40/CUSP/KET. We have investigated the hypotheses that: (a) p63 is mutated in diverse types of human cancers; and (b) p63 functions in the same pathway as p53 and p73 in the process of carcinogenesis; therefore, mutations in these three genes would be mutually exclusive. We have analyzed the genomic structure of the p63 gene and have performed mutational analyses on 54 human cell lines using intronic primers flanking each exon. We have confirmed that the human p63 open reading frame encodes the same length of protein as murine p63 that was initially reported to be 39 amino acids longer than human p63. By mutational analysis, we have shown that DLD1 and SKOV3 cells have either heterozygous mutations or polymorphisms in the putative DNA binding domain of p63. In these cell lines, p63 is biallelically expressed. We conclude that mutations in the p63 gene are rare in human cell lines. The fact that DLD1 is abnormal for both p63 and p53 genes suggests that they may not be involved in the same tumor suppressor pathway.
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PMID:Mutational analysis of the p63/p73L/p51/p40/CUSP/KET gene in human cancer cell lines using intronic primers. 1048 47

We have identified a new human p53 homologue, p40 (p51/p63). This gene was mapped to the distal arm of 3q and was found to be essential for normal epithelial development. We used microsatellite and FISH analyses to search for genetic alterations of p40 in primary HNSCC. A more precise localization of p40 was completed using 6 known markers on 3q and a newly isolated microsatellite marker within the p40 gene. We also determined the genomic organization of the p40 gene using human YAC and BAC clones. Microsatellite analysis revealed that 14 of 26 (54%) primary HNSCC had allelic imbalance in at least 1 of the 7 microsatellite loci. However, FISH analysis with a p40 probe showed that a majority of HNSCC had an increased copy number of the locus regardless of allelic status. Thus, overrepresentation of the p40 locus may play an important role in the development of HNSCC.
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PMID:Frequent gain of the p40/p51/p63 gene locus in primary head and neck squamous cell carcinoma. 1079 91

We and others recently isolated a human p53 homologue (p40/p51/p63/p73L) and localized the gene to the distal long arm of chromosome 3. Here we sought to examine the role of p40/p73L, two variants lacking the N-terminal transactivation domain, in cancer. Fluorescent in situ hybridization (FISH) analysis revealed frequent amplification of this gene locus in primary squamous cell carcinoma of the lung and head and neck cancer cell lines. (We named this locus AIS for amplified in squamous cell carcinoma.) Furthermore, amplification of the AIS locus was accompanied by RNA and protein overexpression of a variant p68(AIS) lacking the terminal transactivation domain. Protein overexpression in primary lung tumors was limited to squamous cell carcinoma and tumors known to harbor a high frequency of p53 mutations. Overexpression of p40(AIS) in Rat 1a cells led to an increase in soft agar growth and tumor size in mice. Our results support the idea that AIS plays an oncogenic role in human cancer.
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PMID:AIS is an oncogene amplified in squamous cell carcinoma. 1080 2


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