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Query: UMLS:C0009443 (cold)
 92,137 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the phosphorylation of cellular phosphoproteins and, in more detail, of SV40 T antigen and the cellular protein p53 in SV40 tsA-transformed cells. As detected by radiolabeling cold-sensitive tsA1499- or heat-sensitive tsA58-transformed rat fibroblasts with [32P]orthophosphate or by in vitro labeling extracts with [gamma-32P]ATP the hyperphosphorylation of certain cellular phosphoproteins including p53 and also of free SV40 large T antigen and T antigen complexed with p53 is strictly correlated with the expression of the transformed phenotype. This hyperphosphorylation can be observed as early as 30 min after shifting to the temperature where the cells expressed the transformed phenotype and, furthermore, it is dependent on protein synthesis. To evaluate the influence of a functional T antigen and to exclude properties of individual transformants we 32P labeled in vitro cellular proteins from rat F111, mouse NIH 3T3, and monkey TC-7 cells infected with tsA58 or tsA1499. In tsA58-infected cells we found a heat-sensitive enhancement of protein phosphorylation just as in tsA58 transformants. In tsA1499-infected monkey cells we observed a heat-sensitive and in abortively infected rat or mouse cells a cold-sensitive hyperphosphorylation of proteins. Thus in tsA-transformants and in various tsA-infected cells we found a strong correlation among the transformed phenotype, functions of T antigen, and the phosphorylation of various cellular proteins and in particular T antigen and p53.
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PMID:Enhanced protein phosphorylation in SV40-transformed and -infected cells. 282 83

F111 rat cells transformed by simian virus 40 mutant tsA1499 are cold sensitive for the expression of transformation. Yet, unlike F111 cells transformed by tsA58, they do not lose the ability to stabilize the transformation-associated host cell protein p53 at the temperature at which transformation is extinguished.
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PMID:Large-T-antigen-p53 complex formation is not cold sensitive in a cold-sensitive transformant induced by simian virus 40 mutant tsA1499. 632 80

The availability of antibodies which recognise p53 protein in paraffin-embedded tissue has created the opportunity to use immunohistochemistry to study the expression of p53 in a wide variety of clinical material. In this paper we have investigated the relationship between the type of fixative and the pattern of p53 staining in mammary carcinoma. Optimal results were obtained from breast tissue fixed in phenol formol saline, methacarn or cold formol saline with positive staining for stabilised p53 protein occurring in 69/95 (73%) cases studied. Care must be taken in the interpretation of these results since positive staining for p53 protein is not always indicative of mutation of the p53 gene. Furthermore, a range of staining patterns is seen in mammary carcinomas, making interpretation difficult. Assessment of staining needs to be standardised in order that different studies can be compared. However, in breast carcinoma, p53 immunohistochemistry appears to give information relating to tumour grade and, independently, to prognosis.
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PMID:Problems with p53 immunohistochemical staining: the effect of fixation and variation in the methods of evaluation. 750 24

p53 is an allosterically regulated protein with a latent DNA-binding activity. Posttranslational modification of a carboxy-terminal regulatory site in vitro, by casein kinase II and protein kinase C, can activate the sequence-specific DNA-binding function of the wild-type protein. The latent form of p53 is produced in a variety of eukaryotic and prokaryotic cell lines, including E. coli, Sf9 insect cells, and C6 cells, indicating that the activation of p53 in vivo is rate-limiting. In addition, phosphorylation of p53 at the protein kinase C site and activation in vivo correlate with the loss of reactivity of active p53 protein to the carboxy-terminal antibody, PAb421. These results suggest that two highly conserved protein kinases modify polypeptide structure through a common biochemical mechanism and that different enzymatic pathways may channel information into the carboxy-terminal regulatory site of p53, allosterically activating its function as a tumor suppressor.
Cold Spring Harb Symp Quant Biol 1994
PMID:Regulation of the cryptic sequence-specific DNA-binding function of p53 by protein kinases. 758 70

A number of genetic changes have been documented in prostate cancer, ranging from allelic loss to point mutations and changes in DNA methylation patterns (summarized in Fig. 1). To date, the most consistent changes are those of allelic loss events, with the majority of tumors examined showing loss of alleles from at least one chromosomal arm. The short arm of chromosome 8, followed by the long arm of chromosome 16, appear to be the most frequent regions of loss, suggesting the presence of novel tumor suppressor genes. Deletions of one copy of the Rb and p53 genes are less frequent, as are mutations of the p53 gene, and accumulating evidence suggests the presence of an additional tumor suppressor gene on chromosome 17p, which is frequently inactivated in prostate cancer. Alterations in the E-cadherin/alpha-catenin-mediated cell-cell adhesion mechanism appear to be present in almost half of all prostate cancers and may be critical to the acquisition of metastatic potential of aggressive prostate cancers. Finally, altered DNA methylation patterns have been found in the majority of prostate cancers examined, suggesting widespread alterations in methylation-modulated gene expression. The presence of multiple changes in these tumors is consistent with the multistep nature of the transformation process. Finally, efforts to identify prostate cancer susceptibility loci are under way and may elucidate critical early events in prostatic carcinogenesis.
Cold Spring Harb Symp Quant Biol 1994
PMID:Genetic alterations in prostate cancer. 758 26

Inactivation of the p53 tumor suppressor gene appears to be an important event in the progression of many types of human neoplasms; however its role in rodent experimental tumorigenesis is controversial. Previous studies have shown that a wide array of chemically induced and spontaneous mouse liver tumors lack p53 mutations within the evolutionarily conserved regions of exons 5-8. However, since p53 inactivation in human neoplasms occurs relatively late in tumor progression, it is possible that the mouse liver tumors evaluated previously were not suitably advanced to incur p53 aberrations. In the present study, we examined an end-stage, highly malignant embryonal mouse liver tumor known as the hepatoblastoma (HB) for p53 mutations utilizing the highly sensitive 'cold' single-strand conformation polymorphism (SSCP) technique. In addition, several of the HBs were examined by direct nucleotide sequencing. No aberrations of the p53 gene were detected within exons 5-8 of any of the 16 HBs examined. These results confirm that the p53 gene plays a minimal role in the development or malignant progression of hepatocellular tumors in mice.
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PMID:Lack of p53 point mutations in chemically induced mouse hepatoblastomas: an end-stage, highly malignant hepatocellular tumor. 765 27

A rapid (< 2.5 hrs) method for single-strand conformation polymorphism (SSCP) analysis of PCR products that allows the use of ethidium bromide staining is described. PCR products ranging in size from 117 to 256 bp were evaluated for point mutations and polymorphisms by 'cold SSCP' in commercially available pre-cast polyacrylamide mini-gels. Several electrophoretic parameters (running temperature, buffers, denaturants, DNA concentration, and gel polyacrylamide concentration) were found to influence the degree of strand separation and appeared to be PCR fragment specific. Use of the 'cold' SSCP technique and the mini-gel format allowed us to readily optimize the electrophoretic conditions for each PCR fragment. This greatly increased our ability to detect polymorphisms compared to conventional, radioisotope-labeled 'hot' SSCP, typically run under two standard temperature conditions. Excellent results have been obtained in resolving mutant PCR fragments from human p53 exons 5 through 8, human HLA-DQA, human K-ras exons 1 and 2, and rat K-ras exon 3. Polymorphisms could be detected when mutant DNA comprised as little as 3% of the total gene copies in a PCR mixture. Compared to standard 'hot' SSCP, this novel non-isotopic method has additional advantages of dramatically increased speed, precise temperature control, reproducibility, and easily and inexpensively obtainable reagents and equipment. This new method also lacks the safety and hazardous waste management concerns associated with radioactive methods.
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PMID:'Cold SSCP': a simple, rapid and non-radioactive method for optimized single-strand conformation polymorphism analyses. 836 79

Mutations in the p53 tumor suppressor gene have been implicated in the pathogenesis of a wide variety of human neoplasms. The location and types of p53 gene mutation can reflect exposure of humans to certain types carcinogenic agents. Much less is known about the role of p53 mutational inactivation in rodent tumors. Using both 'Hot' (radioactive) and 'Cold' (non-radioactive) single strand conformation polymorphism (SSCP) analyses, the present study of analyzed exons 5-8 and the exon-intron junction of the p53 gene from rat esophageal papillomas induces by N- nitrosomethylbenzylamine (NMBA) for mutations. Nine of 30 (30%) esophageal papillomas contained SSCP mobility shifts, principally within exons 5 and 7. These positive SSCP findings were further validated by direct DNA sequencing analysis. Eight of the nine mutations were G:C-->A:T transitions in codons 131, 149, 153, 242 (2), 243, 248, and the 5 end of intron 7. None of these G:C-->A:T mutations occurred at the CpG sites. The other mutation was a frameshift mutation in codon 176. The G:C-A:T transitions observed in this study are consistent with the documented formation of O(6)-methylguanine adducts in DNA N-nitroso compounds. These results suggest that point mutations of the p53 gene are involved in the development of approximately one-third of NMBA-induced rat esophageal papillomas. 'Hot' and 'Cold' SSCP methods were equally sensitive for the identification of mutations in the rat p53 gene.
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PMID:Mutation in the p53 tumor suppressor gene in rat esophageal papillomas induced by N-nitrosomethylbenzylamine. 862 69

Tumor suppressor genes such as Rb and p53 usually kill tumor cells when overexpressed ectopically. This is a consequence of their normal cell cycle regulatory functions. By contrast, the E1a gene of adenovirus, a common cold virus, converts tumor cells into viable normal cells. This has advantages for investigation and control of cancer. In particular, E1a is a master programmer of the epithelial phenotype. This provides a new tool for understanding the molecular basis of the epithelial-mesenchymal transition, and how it goes awry in cancer cells. Furthermore, epithelial cells are sensitive to a form of apoptosis - 'anoikis' - that is induced by detachment from extracellular matrix. This property confers strict anchorage-dependence. Transcriptional programming, by E1a or the formation of cell-cell junctional complexes, programs epithelial cells to be sensitive to anoikis.
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PMID:Reversal of malignancy by the adenovirus E1a gene. 865 90

In the cold winter of 1966 Aleksay Olovnikov, a theoretical biologist at the Academy of Sciences in Moscow, was waiting in the subway station where he was hit by the idea that the ends of linear chromosomes can't be replicated fully during each round of replication. In a theoretical paper (Olovnikov, 1971) he proposed that in somatic cells the ends of the chromosomes are not fully replicated during DNA synthesis, resulting in the shortening of linear DNA molecules with each cell division, and that this may be the cause of cell cycle arrest in senescent cells. Almost two decades after this proposal, Calvin Harley and co-workers found that telomeres, the physical ends of human chromosomes, shorten as a function of age in human cells in vitro and in vivo. The telomere hypothesis proposes that critically short telomeres may act as a mitotic clock to signal the cell cycle arrest at senescence (Harley, 1991). Here, we extend the telomere hypothesis and propose a model that incorporates recent advances in tumor suppressors and cell cycle control with several areas of cell aging. We propose that telomere shortening per se is not the direct signal for cell cycle arrest. It is the consequence of telomere loss, which may lead to generation of ds or ss DNA breaks. These breaks activate a p53 dependent or independent DNA-damage pathway that leads to the induction of a family of inhibitors of cyclin dependent kinases (including p21 and p16) and the eventual G1 block of senescence. In agreement with this hypothesis, we demonstrate that the level of p53 protein increases in near senescent cultures of MDFs. This increase may be responsible for induction of p21 (Noda, 1993) and IGF-Bp3 (Goldstein, 1991).
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PMID:From telomere loss to p53 induction and activation of a DNA-damage pathway at senescence: the telomere loss/DNA damage model of cell aging. 870 99


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