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)

Correlation between the expression of growth factor/receptor systems or the alterations of tumor suppressor genes and biological malignancy of gastric cancer was described. Overexpression of many growth factors/receptors, such as EGF, TGF alpha, EGF receptor and ERBB2, and reduction of type I receptor for TGF beta may be linked with new prognostic factors of gastric carcinomas. The expression of cripto, a novel gene of EGF family, shows a tendency to correlate with tumor staging of well differentiated gastric adenocarcinomas. p53 gene abnormalities take place in 60% of gastric carcinomas including early stage carcinoma. Loss of heterozygosity on chromosomes 1q, 7p and 7q is frequently observed in advanced gastric carcinomas of well differentiated type. Molecules which regulate tumor invasion and metastasis such as nm23, tissue inhibitor of metalloproteinase (TIMP) and endogenous galactoside-binding lectin may provide for prognostic factors of gastric cancer.
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PMID:[New prognostic factors in human gastric carcinomas]. 134 86

Regulatory regions controlling p53 gene transcription in Syrian hamster embryo cells were characterized by use of chloramphenicol acetyl-transferase (CAT) constructs encompassing various subfragments of its 5'-flanking sequences. This analysis identified a 961 bp PstI-SacI (PS) fragment upstream from the p53 P1 promoter, which exhibited promoter activity only in the reverse orientation relative to the p53 gene. Northern hybridizations of mRNA from hamster embryo cells with genomic probes containing the PS fragment detected a 2.1-kb transcript expressed at much lower levels than the p53 mRNA. Steady-state levels of the 2.1-kb mRNA were threefold higher in actively growing cells than in cells from confluent cultures. Library screenings with PS-containing probes resulted in the isolation from exponentially growing cells of a cDNA, the nucleotide sequence of which showed no significant homology to genes previously described. This novel gene, named Gnb5, for guanine nucleotide-binding protein, beta 5, codes for a protein of 538 amino acids with a highly acidic amino terminus containing a proline-rich domain, followed by a neutral domain with five repeat units of the beta-transducin (WD-40) motif. The homology with beta subunits of G proteins and with other WD-40 repeat-containing proteins was restricted to the repeats. The Gnb5 gene is well conserved in rodents and primates, as the hamster Gnb5 cDNA recognized, under high stringency conditions, the human and mouse counterparts in Southern and Northern hybridizations. Expression of Gnb5 in adult tissues was detected preferentially in testes, in both hamsters and humans.
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PMID:The Gnb5 gene is a novel beta-transducin homolog transcribed from a divergent promoter located immediately upstream of the Syrian hamster p53 P1 promoter. 761 25

Hyperplastic lesions of the oropharyngeal mucosa such as leukoplakia and oral lichen planus can eventually develop into squamous cell carcinomas (SCC) and provide an excellent model for multistage carcinogenesis. The development of carcinomas is assumed to be the result of the interaction of genetic factors, locally applied carcinogens and immunological unresponsiveness. Recently a novel gene termed mdm2 has been isolated that is found to be involved in transcriptional regulation and can inhibit p53 function by forming a complex with p53. In this study the immunohistochemical detection of the MDM2 protein in 186 paraffin embedded tissue sections of normal mucosa, premalignant, malignant and metastatic lesions of the oropharyngeal mucosa is reported for the first time. p53 protein expression was also investigated in the same tissue samples. The increase in the number of p53 and MDM2 positive biopsies was correlated with the dysplasia grade and the loss of differentiation in the premalignant and malignant lesions. In late stages of the disease the number of biopsies that expressed both p53 and MDM2 increased. Inactivation of p53 function in head and neck carcinogenesis may also be due to MDM2 binding. Detection of MDM2 protein expression by immunohistochemistry may be an important diagnostic tool in the future.
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PMID:Detection of p53 and MDM2 protein expression in head and neck carcinogenesis. 765 34

To search for candidate genes involved in p53-mediated apoptosis, the differential display technique was used to identify RNA species whose expression was altered in murine NIH3T3 cells treated with the cytotoxic drug etoposide. We report here the isolation and characterization of EI24, a novel gene whose 2.4 kb mRNA is induced following etoposide treatment. Induction of EI24 mRNA by etoposide required expression of wild-type p53 in murine embryonic fibroblasts which had been transformed with the oncogenes E1A and T24 H-ras; and overexpression of functional p53 in these cells was sufficient to induce expression of the EI24 mRNA. The EI24 mRNA was also induced in a p53-dependent manner by ionizing irradiation of primary murine thymocytes. Isolation of a full-length EI24 cDNA revealed that its protein product bears homology to CELF37C12.2, a Caenorhabditis elegans protein of unknown function.
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PMID:Identification and cloning of EI24, a gene induced by p53 in etoposide-treated cells. 864 19

We have identified a novel gene inducible by wild-type p53. A significant correlation between expression of this gene and p53 status in cells derived from esophageal cancers indicated that this gene is likely to be specifically regulated in a p53-dependent manner. As the predicted amino acid sequence showed a high degree of homology to the family of glycosyl-phosphatidylinositol (GPI)-anchored membrane proteins, we termed this gene GML (GPI-anchored molecule-like protein). Introduction of GML cDNA suppressed the growth of esophageal cancer cells in culture. A correlation between the presence of GML expression and the sensitivity of esophageal cancer cells to anti-cancer drugs implied that the gene product plays a significant role in the apoptotic pathway or cell-cycle regulation induced by p53 after DNA damage.
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PMID:Isolation of a novel GPI-anchored gene specifically regulated by p53; correlation between its expression and anti-cancer drug sensitivity. 893 43

Among its known functions, tumor suppressor gene p53 serves as a transcriptional regulator and mediates various signals through activation of downstream genes. We recently identified a novel gene, GML (glycosylphosphatidylinositol (GPI)-anchored molecule-like protein), whose expression is specifically induced by wildtype p53. To characterize the GML gene further, we determined 35.8 kb of DNA sequence that included a consensus binding sequence for p53 and the entire GML gene. The GML gene consists of four exons; and the p53-binding sequence is present in the 5'-flanking region. In genomic organization this gene resembles genes encoding murine Ly-6 glycoproteins, a human homologue of the Ly-6 family called RIG-E, and CD59; products of these genes, known as GPI-anchored proteins, are variously involved in signal transduction, cell-cell adhesion, and cell-matrix attachment. FISH analysis revealed that the GML gene is located on human chromosome 8q24.3. Genes encoding at least two other GPI-anchored molecules, E48 and RIG-E, are also located in this region.
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PMID:Genomic structure and chromosomal localization of GML (GPI-anchored molecule-like protein), a gene induced by p53. 916 50

Exposure of mammalian cells to ionizing radiation (IR) induces a complex array of cellular responses including cell cycle arrest and/or apoptosis. IR-induced G1 arrest has been shown to depend on the presence of the tumor suppressor p53, which acts as a transcriptional activator of several genes. p53 also plays a role in the induction of apoptosis in response to DNA damage, and this pathway can be activated by both transcription-dependent and -independent mechanisms. Here we report the identification of a novel transcript whose expression is induced in response to IR in a p53-dependent manner, and that shows homology to the type 2C protein phosphatases. We have named this novel gene, wip1. In vitro, recombinant Wip1 displayed characteristics of a type 2C phosphatase, including Mg2+ dependence and relative insensitivity to okadaic acid. Studies performed in several cell lines revealed that wip1 accumulation following IR correlates with the presence of wild-type p53. The accumulation of wip1 mRNA following IR was rapid and transient, and the protein was localized to the nucleus. Similar to waf1, ectopic expression of wip1 in human cells suppressed colony formation. These results suggest that Wip1 might contribute to growth inhibitory pathways activated in response to DNA damage in a p53-dependent manner.
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PMID:Wip1, a novel human protein phosphatase that is induced in response to ionizing radiation in a p53-dependent manner. 917 66

The human RAD51 protein is a homologue of the bacteria RecA and yeast RAD51 proteins that are involved in homologous recombination and DNA repair. RAD51 interacts with proteins involved in recombination and also with tumor suppressor proteins p53 and breast cancer susceptibility gene 1 (BRCA1). We have used the yeast two-hybrid system to clone murine cDNA sequences that encode two RAD51-associated molecules, RAB22 and RAB163. RAB163 encodes the C-terminal portion of mouse BRCA2, the homologue of the second breast cancer susceptibility gene protein in humans, demonstrating an in vitro association between RAD51 and BRCA2. RAB22 is a novel gene product that also interacts with RAD51 in vitro. To detect RAD51 interactions in vivo, we developed a transient nuclear focus assay that was used to demonstrate a complete colocalization of RAB22 with RAD51 in large nuclear foci.
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PMID:RAB22 and RAB163/mouse BRCA2: proteins that specifically interact with the RAD51 protein. 919 68

Through cloning of functional p53-binding sites (p53-tagged sites) from the human genome, we isolated a novel gene inducible by wild-type p53. Its cDNA sequence contained an open reading frame encoding a 431-amino acid peptide that showed a significant homology with members of the P2X family. This protein also revealed a similarity to RP-2, a gene activated in thymocytes undergoing programmed cell death. Northern blot analysis showed that it was expressed predominantly in skeletal muscle. Hence, we designated the gene P2XM (P2X specifically expressed in skeletal muscle). P2XM was localized to chromosomal band 22q11, where frequent loss of heterozygosity has been observed in rhabdoid tumors. Although we detected no genetic alteration in the coding sequences, one of four rhabdomyosarcoma cell lines examined had completely lost expression of this gene. Furthermore, a minor splice variant lacking a part of exon 1 that would encode residues corresponding to transmembrane domain M1 was relatively more abundant in two of seven sarcoma cell lines, one of which was derived from a rhabdomyosarcoma, and the other was derived from an osteosarcoma. The results suggest that P2XM may play a significant role in the proliferation and/or differentiation of skeletal muscle cells and that its altered expression may be involved in the development of some sarcomas.
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PMID:Cloning of P2XM, a novel human P2X receptor gene regulated by p53. 924 61

Recently we identified a novel gene, gml, whose expression is regulated in a p53-dependent manner and found that gml expression was correlated with the sensitivity of esophageal cancer cells to anticancer drugs. To further investigate the biological mechanism of gml in determining the chemosensitivity of cancer cells to clinically useful agents, we introduced gml cDNA into TE10, an esophageal cancer cell line that lacks endogenous gml expression. In two resulting stable cell lines which expressed gml cDNA in the absence of wildtype p53, cell death occurred within 6 h after treatment with Taxol. TE10 parent cells or TE10 cells transfected with vector alone displayed relative resistance for 36 h. Induction of gml did not by itself affect viability. Morphological analysis confirmed that the increased chemosensitivity to Taxol conferred by gml was due to apoptosis. These data suggest that reduced expression of gml is likely to be associated with poor response rates to chemotherapy, and that an assay for gml expression might serve a clinical purpose as a predictor of chemotherapeutic sensitivity.
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PMID:GML sensitizes cancer cells to Taxol by induction of apoptosis. 931 6


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