Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of nine proto-oncogenes (c-myc, N-myc, c-fos, c-jun, p53, H-ras, N-ras, c-raf, hst) and other three genes (AFP, PCNA, GST-P) were investigated during spontaneous development to hepatocellular carcinomas (HCCs) in LEC rats. Expressions of c-myc, H-ras, N-ras, c-raf, p53, and PCNA genes were detected but did not significantly change during the development to HCCs in LEC rats. Expressions of N-myc, hst, and AFP genes were not detectable since 5 weeks after birth. Expression of c-fos gene was detected in one out of four HCCs. Significantly increased expression of c-jun gene was observed in the liver tissues of LEC rats aged 8 months. The high expression was decreased in HCCs. On the other hand, the expression of GST-P gene increased in parallel with the clinical course of the development to HCCs in LEC rats. The increased expression of GST-P gene was observed in the liver tissues of LEC rats aged 8 months, and HCCs showed very high expression of GST-P gene. These observations suggest that both c-jun and GST-P genes may play a role in the spontaneous development to HCCs in LEC rats.
 ...
PMID:[A study on expression of various oncogenes and tumor-associated genes in LEC rats spontaneously developing hepatitis and hepatoma]. 169 10

The murine B-cell hybridoma B9 requires interleukin-6 (IL-6) for its survival and proliferation in vitro. We show here that withdrawal of IL-6 from B9 cultures results in programmed death, concomitant with arrest of the cells in the G1 phase of the cell cycle. Unlike several other systems that undergo programmed cell death, no induction of transcripts corresponding to the testosterone-repressed message-2 or transglutaminase genes is observed during this process. Upon readdition of IL-6 to G1-arrested B9 cells, viability is maintained and entry into S phase occurs after a lag period of 10 to 12 hr. Northern blot analysis showed that the immediate-early mRNAs normally induced shortly after growth factor stimulation in quiescent fibroblasts (c-fos, c-jun, Egr-1, c-myc, JE, and KC), and other growth-related genes (2F1, c-Ha-ras, and p53), are either not induced or remain unchanged during G1 to S phase progression. A correlation was found, however, between the temporal pattern of expression of several G1/S phase genes (dihydrofolate reductase, thymidine kinase, transferrin receptor, and histone H3) and DNA synthesis. These results demonstrate that IL-6-induced viability and growth of hybridoma (and, presumably, plasmacytoma) cells is mediated via novel signal transduction pathways.
 ...
PMID:Suppression of programmed death and G1 arrest in B-cell hybridomas by interleukin-6 is not accompanied by altered expression of immediate early response genes. 170 72

The myeloid interleukin-3 (IL-3) dependent cell line, FDC-P1, enters the G0 stage of the cell cycle after IL-3 deprivation for 24 hr. The expression of 13 protooncogenes and immediate-early genes was compared with 4 "control" genes after the addition of either IL-3 or phorbol myristate acetate (PMA) to IL-3-deprived cells. mRNA transcripts encoding c-myc and the T-cell receptor c-gamma gene were induced to high levels only after IL-3 addition, whereas c-fos, fos-B, c-jun, jun-B, Krox-20, and Krox-24 were induced transiently only after PMA addition. The remaining genes (fra-1, p53, jun-D, c-Ha-ras, c-Ki-ras, c-raf, beta-actin, ornithine decarboxylase, and histone 2B) were detected after culture with either IL-3 or PMA. When cells were serum- and IL-3-deprived, c-fos, fos-B, c-jun, jun-B, Krox-20, and Krox-24 were detected after exposure to either serum or PMA. Moreover, culture with cycloheximide and PMA resulted in superinduction of these genes, whereas cycloheximide and IL-3 addition did not. mRNAs encoding these genes had half-lives of 10-20 min after PMA treatment, whereas that of beta-actin was longer (greater than 2 hr), suggesting that short mRNA half-lives contributed to the transient nature of these genes. Although c-fos, fos-B, c-jun, jun-B, Krox-20, and Krox-24 expression can be detected in IL-3-dependent cells after exposure to either PMA or serum, these genes were not detected after IL-3 addition, which allows cell-cycle progression. These results document the existence of IL-3 and PMA-responsive genes and demonstrate that IL-3 and protein kinase C agonists can induce distinct patterns of gene expression.
 ...
PMID:Interleukin-3 and phorbol esters induce different patterns of immediate-early gene expression in an interleukin-3 dependent cell line. 170 18

Nuclear oncoproteins are among the most rapidly degraded intracellular proteins. Previous work has implicated the ubiquitin-mediated proteolytic system in the turnover of short-lived intracellular proteins. In the present study, we have evaluated the potential role of the ubiquitin system in the degradation of the specific nuclear oncoproteins encoded by the N-myc, c-myc, c-fos, p53 and E1A genes. Each of these nuclear oncoproteins was synthesized in vitro by transcription of the appropriate cDNA and translation of the resulting mRNA in the presence of [35S]methionine. Degradation of labeled proteins was monitored in the ubiquitin cell-free system. ATP stimulated the degradation of all the proteins between 3- and 10-fold. The degradation was completely inhibited by neutralizing antibody directed against the ubiquitin-activating enzyme, E1, the first enzyme in the ubiquitin-mediated proteolytic cascade. Moreover, degradation in E1-depleted lysates could be restored in each case by the addition of affinity-purified E1. These data suggest that the ubiquitin system mediates the degradation of these oncoproteins in vitro. Degradation of other proteins, such as superoxide dismutase, cytochrome c, enolase, RNase A, and ornithine decarboxylase, is not mediated by the ubiquitin cell-free system. This suggests that the nuclear oncoproteins studied here possess specific signals that target them for rapid turnover by this proteolytic pathway. Furthermore, the relative sensitivity to degradation of various E1A mutants in vivo is also maintained in the cell-free system, suggesting that the ubiquitin pathway may play a role in the cellular degradation of these proteins as well.
 ...
PMID:Degradation of nuclear oncoproteins by the ubiquitin system in vitro. 184 34

The inherited cancer-inducing disease familial polyposis coli (FPC) provides an excellent model not only for studying tumor progression in colorectal cancer but also for elucidating molecular mechanisms in general oncogenesis. This paper reviewed recent remarkable progresses of molecular mechanisms in colorectal tumorigenesis. This is concerned with the various kinds of genetic alterations that accumulate in the development from normal mucosa to adenoma, and then to adenocarcinoma in comparison with FPC and sporadic cases. This review included also information on the localization of FPC major gene. These observations indicate that in cases of colorectal tumorigenesis several genetic alterations may be involved, including activation of K-ras gene, deregulated expression of c-myc gene or c-fos gene and inactivation of tumor suppressor genes such as p53 and DCC genes, as well as the loss of heterozygosity. The observation suggest that adenomas will have undergone several gene or chromosome mutations before reaching to the fully malignant state. Therefore, DNA diagnosis for colorectal tumors in the clinical level may contribute to more accurate prognosis and better results for further therapy.
 ...
PMID:[Diagnosis of colorectal cancer from DNA level]. 184 82

Normal human diploid fibroblasts, TIG-1, which have a replicative life span of about 62 population doublings (PD), tended to senesce after about 50 PD with a gradual decrease in sensitivity to serum. Treatment of TIG-1 cells with the antisense-Rb oligomer, which completely depleted the retinoblastoma susceptibility gene product (RB), extended life span by about 10 PD. Treatment with the antisense-p53 oligomer alone had no effect; however, cotreatment with the antisense-Rb oligomer further potentiated the extension and the increased sensitivity to serum caused by the antisense-Rb oligomer alone, suggesting that p53 and RB function in separate, yet complementary pathways in signal transduction to senescence. The c-fos expression, which is presumed to be regulated negatively by RB, was not stimulated in partially senescent TIG-1 cells by treatment with the antisense-Rb oligomer.
 ...
PMID:Cooperative effect of antisense-Rb and antisense-p53 oligomers on the extension of life span in human diploid fibroblasts, TIG-1. 190 21

The wild-type (wt) p53 protein is the product of a tumor suppressor gene that is a frequent target for inactivation in many types of tumors. The nuclear localization of the protein, as well as additional features, suggest that it may be involved in the regulation of gene expression. To explore this possibility, the effects of overproduced wt p53 were investigated in a number of systems. Induction of growth arrest via the antiproliferative effect of wt p53 greatly impaired the ability of cells to exhibit an increase in c-fos mRNA upon serum stimulation. Experiments in which cells were cotransfected with p53 expression plasmids together with a reporter gene linked to various promoters revealed that wt p53 could effectively reduce transcription from a series of promoters derived from serum-inducible genes, but not from a major histocompatibility complex gene. The p53-mediated repression of c-fos gene expression occurred even in the presence of cycloheximide. Kinetic studies indicate that the effect of wt p53 is rapid, rather than representing a secondary consequence of growth arrest. These findings support a role for p53 in transcriptional regulation, perhaps by reducing the expression of genes that are needed for ongoing cell proliferation.
 ...
PMID:Wild-type p53 can down-modulate the activity of various promoters. 194 67

We have studied the expressions of nine proto-oncogenes (c-myc, N-myc, c-fos, C-jun, p53, H-ras, N-ras, c-raf, hst) and two other genes (PCNA, GST-P) during the spontaneous development of hepatocellular carcinomas (HCCs) in LEC rats. Expression of c-myc, H-ras, N-ras, C-raf, p53 and PCNA genes was detected, but this did not significantly change during the development of HCCs in LEC rats. Expression of N-myc and hst genes was not detectable. Expression of c-fos gene was detected in one HCC case out of four. Significantly increased expression of c-jun gene was observed in the liver tissues of LEC rats aged 8 months. This high expression was decreased with the development of HCCs. On the other hand, the expression of GST-P gene increased in parallel with the clinical course of the development of HCCs in LEC rats. The pattern of c-jun mRNA augmentation was different from that of GST-P mRNA. These observations suggest that c-jun gene may play a role in the spontaneous development of HCCs in LEC rats.
 ...
PMID:Increased expression of c-jun gene during spontaneous hepatocarcinogenesis in LEC rats. 197 34

Smooth muscle cells in the thickened intima of the aorta also expressed sis, mye, and c-fos, in addition to collagen types I, III, IV and type V. In the cultures of smooth muscle cells isolated from human aorta, collagen I, III and gelatinase were produced without any other special conditions for the culture. In the presence of PDGF, collagen type V and collagenase production was detected in the culture. Oncogene expression was not detected in the cultured cells when tested by the indirect immunofluorescence technique. Immortalized smooth muscle cells with SV 40 expressed myc, SV 40 large T antigen, and p53 without inhibition of collagen and collagenolytic enzymes production.
 ...
PMID:[Expression of oncogenes by smooth muscle cells in atherosclerotic lesions]. 215 35

We have used a system of nutritional manipulation to investigate whether hepatocytes of the normal liver can be primed for replication in vivo. In this system, rats that are denied protein for 3 days undergo a burst of hepatic DNA synthesis and mitosis when they are refed amino acids, while normally fed or starved rats do not respond. To determine if hepatocytes of protein deprived (PD) rats have been "primed" for replication, we examined changes in protooncogene expression in livers of PD rats to see if they would mimic the pattern of gene expression that is induced early after partial hepatectomy. c-jun, c-myc, and p53 mRNAs were elevated in livers of PD rats, while c-fos and c-ras genes were not expressed. The administration of amino acids to PD rats stimulated hepatic DNA synthesis in a shorter period than is required after partial hepatectomy and induced p53 and c-ras expression. In culture, hepatocytes from PD rats had higher levels of c-myc mRNA, underwent morphological changes more rapidly, and reached maximum rates of DNA synthesis earlier than normal hepatocytes. In both normal and primed hepatocyte cultures, transforming growth factor alpha stimulated DNA synthesis more effectively than epidermal growth factor. We conclude that hepatocytes pass through a priming stage before they proliferate and that replicative competence without DNA synthesis can be induced in hepatocytes in the normal liver.
 ...
PMID:Induction of replicative competence ("priming") in normal liver. 220 69


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>