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)

The panel of 70 transformed clones was isolated after exposure of C3H/10T1/2 cells in stationary phase to low-moderate doses (1-4 Gy) of 137Cs gamma-rays. Two widely different dose rates were used: high (HDR, 0.66 Gy/min) and low (LDR, 4.8 x 10(-4) Gy/min). Immunohistochemical analyses were performed by cellular staining with three types of monoclonal anti-p53 antibodies, Ab-1 (PAb421), Ab-3 (PAb240) and Ab-4 (PAb246) in order to identify wild-type and altered conformation of the p53 protein in cell nuclei. The gamma-ray exposure led to induction of altered p53 protein in the majority of morphologically transformed clones. For LDR exposure the percentage of clones with changed p53 protein was 79 (11/14), 71 (12/17) and 100 (6/6) for the exposure doses of 2, 3 and 3.6 Gy, respectively. For HDR exposure the percentage of such clones was 60 (3/5), 40 (4/10) and 87 (13/15) for 1, 2 and 3 Gy, respectively. Moreover, in some transformed clones, especially in those induced by higher gamma-ray doses, p53 protein in cell nuclei was not found. It was demonstrated by lack of the staining with Ab-1 antibody which can detect both mutant and wild-type of p53 protein. An altered conformation of p53 protein was detected, using Ab-3 antibody which does not react with its native conformation, in 27% (18/67) of all radiation-induced clones. A native conformation of p53 protein was recognized by Ab-4 antibody in 33% (10/30) of clones induced by HDR, and in 22% (8/37) of clones induced by LDR exposure. Our study shows that alterations of p53 protein in cell nuclei is a frequent feature of morphological transformations induced by ionizing radiation in C3H/10T1/2 cells, and that these alterations occur independently of dose rate.
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PMID:Alteration of p53 protein in C3H/10T1/2 cells morphologically transformed by gamma-rays in stationary phase. 954 59

Recent data suggest that aberrant function of the wild type p53 protein (WTp53) may alter cellular survival following DNA damage through cellular pathways involving apoptosis and cell-cycle checkpoints, but little is known concerning it's possible role in DNA repair. In the present study, the ionizing radiation sensitivity was determined for a series of rat embryo fibroblast (REF) cell lines transfected with an activated form of the H-ras oncogene alone, or in combination with a variety of missense-mutant p53 (MTp53) alleles. Transformed REF clones which expressed exogenous MTp53 and p21ras proteins (CLASS II clones) were generally radioresistant in culture as determined by higher values for the surviving fraction after 2 Gy (SF2 value) and the radiation dose required to reduce survival to a fraction of 0.1 (D10 value), compared either to transformed REF clones expressing p21ras protein alone (CLASS I clones), or to non-transfected REF control cell lines expressing baseline endogenous levels of p21ras and WTp53 protein. The increased radioresistance observed in the CLASS II clones (following both HDR- and LDR-irradiation), was significantly correlated with increased expression of MTp53 protein, and a decreased radiation-induced G1 arrest response. The variability observed in clonogenic radiosensitivity among REF clones was not explained by differential radiation-induced apoptosis. Using the Comet assay performed after continuous low dose-rate (LDR)-irradiation, MTp53-expressing REF clones were also found to be more proficient at the rejoining of DNA double-strand breaks (DNA-dsb), compared to WTp53-expressing REF clones. These results suggest that an enhanced DNA and cellular repair capacity may, in part, explain the increased radiation survival observed in some MTp53-expressing transformed fibroblasts and tumours.
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PMID:Radioresistant MTp53-expressing rat embryo cell transformants exhibit increased DNA-dsb rejoining during exposure to ionizing radiation. 958 77

Based on the results of previous microarray analyses of murine NIH3T3/PG13Luc cells irradiated with continuous low-dose-rate (LDR) gamma-ray or end-high-dose-rate-irradiations (end-HDR) at the end of the LDR-irradiation period, the inverse dose-rate-effects on gene expression levels were observed. To compare differences of the effects between LDR-irradiation and HDR-irradiation, HDR-irradiations at 2 different times, one (ini-HDR) at the same time at the start of LDR-irradiation and the other (end-HDR), were performed. The up-regulated genes were classified into two types, in which one was up-regulated in LDR-, ini-HDR-, and end-HDR irradiation such as Cdkn1a and Ccng1, which were reported as p53-dependent genes, and the other was up-regulated in LDR- and ini-HDR irradiations such as pro-collagen TypeIa2/Col1a2, TenascinC/Tnc, and Fibulin5/Fbln5, which were reported as extra-cellular matrix-related (ECM) genes. The time dependent gene expression patterns in LDR-irradiation were also classified into two types, in which one was an early response such as in Cdkn1a and Ccng1 and the other was a delayed response such as the ECM genes which have no linearity to total dose. The protein expression pattern of Cdkn1a increased dose dependently in LDR- and end-HDR-irradiations, but those of p53Ser15/18 and MDM2 in LDR-irradiations were different from end-HDR-irradiations. Furthermore, the gene expression levels of the ECM genes in embryonic fibroblasts from p53-deficient mice were not increased by LDR- and end-HDR-irradiation, so the delayed expressions of the ECM genes seem to be regulated by p53. Consequently, the inverse dose-rate-effects on the expression levels of the ECM genes in LDR- and end-HDR-irradiations may be explained from different time responses by p53 status.
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PMID:Inverse dose-rate-effects on the expressions of extra-cellular matrix-related genes in low-dose-rate gamma-ray irradiated murine cells. 1828 61

Human cytomegalovirus (HCMV) is a ubiquitous pathogen capable of causing life threatening consequences in neonates and immune-compromised individuals. HCMV inflicts site-specific double strand breaks (DSBs) in the cellular genome. DNA damage infliction raises the corollary question of virus modulation of DNA repair. We recently reported HDR was stimulated in wt human foreskin fibroblasts (HFFs) during fully permissive infection or expression of the HCMV protein IE1-72 (IE72). These studies have been extended into semi-permissive T98G glioblastoma cells. T98Gs encode a mutant p53, which may contribute to their high baseline rate of HDR. We fully expected HCMV infection to increase HDR in T98Gs, similar to its effects in HFFs. Surprisingly in T98Gs HCMV infection, or sole expression of IE72, decreased HDR by two-fold. Transient expression of wt p53 in T98Gs also reduced HDR by two-fold. Dual transient expression of wt p53 and IE72 restored high baseline HDR levels. GST pulldown experiments revealed that both IE72 and wt p53 bound the important HDR protein, Rad51. We conclude that the expression of certain HCMV proteins can modulate HDR in an infected cell, dependent upon p53 status. We propose a model of the protein interactions explaining this behavior.
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PMID:Modulation of homology-directed repair in T98G glioblastoma cells due to interactions between wildtype p53, Rad51 and HCMV IE1-72. 2457 46

Multiple myeloma (MM) is a genetically complex disease. The past few years have seen an evolution in cancer research with the emergence of next-generation sequencing (NGS), enabling high throughput sequencing of tumors-including whole exome, whole genome, RNA, and single-cell sequencing as well as genome-wide association study (GWAS). A few inherited variants have been described, counting for some cases of familial disease. Hierarchically, primary events in MM can be divided into hyperdiploid (HDR) and nonhyperdiploid subtypes. HRD tumors are characterized by trisomy of chromosomes 3, 5, 7, 9, 11, 15, 19, and/or 21. Non-HRD tumors harbor IGH translocations, mainly t(4;14), t(6;14), t(11;14), t(14;16), and t(14;20). Secondary events participate to the tumor progression and consist in secondary translocation involving MYC, copy number variations (CNV) and somatic mutations (such as mutations in KRAS, NRAS, BRAF, P53). Moreover, the dissection of clonal heterogeneity helps to understand the evolution of the disease. The following review provides a comprehensive review of the genomic landscape in MM.
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PMID:Genomic Aberrations in Multiple Myeloma. 2769 56