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 protein encoded by the wild-type p53 proto-oncogene has been shown to suppress transformation, whereas certain mutations that alter p53 become transformation competent. Fusion proteins between p53 and the GAL4 DNA binding domain were made to anchor p53 to a DNA target sequence and to allow measurement of transcriptional activation of a reporter plasmid. The wild-type p53 stimulated transcription in this assay, but two transforming mutations in p53 were unable to act as transcriptional activators. Therefore, p53 can activate transcription, and transformation-activating mutations result in a loss of function of the p53 protein. The inability of the p53 mutant proteins to activate transcription may enable them to be transformation competent.
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PMID:Transcriptional activation by wild-type but not transforming mutants of the p53 anti-oncogene. 214 64

Statistically significant charge clusters are of infrequent occurrence in all kinds of proteins. In the six standard classes of proto-oncogene products, all of the nuclear class contain a significant charge cluster and several, but not all, of the transmembrane class do, whereas significant charge clusters or patterns are not found in protooncogenes of primarily cytoplasmic location, nor in membrane-bound (src-like) proto-oncogenes, nor in those of the ras family. Among nuclear oncogene families, such as myc, jun, fos, myb, or ets-related, and among homologous proteins across species, the significant charge clusters are part of the most conserved region. These gene families generally have similar charge distributions embodying a significant charge cluster, not of an invariant sign, preceded by a substantial uncharged stretch of predominantly polar residues. The nuclear transforming proteins p53 and p68 also contain significant charge clusters together with long uncharged segments, suggestive of a modular structure of these proteins. The transmembrane oncogene c-mas contains a mixed charge cluster and c-fms displays an unusual (0, +)7 pattern, in both cases positioned within their intracellular activating domain. Distinctive charge configurations for excreted proto-oncogenes are of a mixed character. Possible functions, mechanisms, and associated experimental procedures for studying proteins with anomalous charge distributions are discussed.
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PMID:Charge configurations in oncogene products and transforming proteins. 218 79

The expression of 20 proto-oncogenes was analysed by Northern blotting in four cell lines derived from patients with Hodgkin's disease (L428, L540, CO and DEV) and compared to lymphoid and myeloid leukemia cell lines and normal hematopoietic cells. Expression of the proto-oncogenes c-myc, p53, c-jun, pim-1, lck, c-syn, c-raf and N-ras were detected in Hodgkin's disease derived cell lines and in normal hematopoietic cells. Transcripts of the proto-oncogene c-met were detected in the Hodgkin's derived cell lines L428 and L540 but not in the lymphoid or myeloid leukemia cell lines or in tonsil cells, peripheral blood mononuclear cells and granulocytes. Expression of the proto-oncogenes N-myc and lck were observed in the Hodgkin's derived cell line CO which express T cell receptor genes and in the T cell lines JM and CEM. L428 cells and CO cells expressed aberrant transcripts of the c-fes proto-oncogene. Thus Hodgkin's disease derived cell lines are heterogeneous in their expression pattern of proto-oncogenes, expressing normal and aberrant transcripts of proto-oncogenes which are not found in untransformed hematopoietic cells.
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PMID:Heterogeneous expression of proto-oncogenes in Hodgkin's disease derived cell lines. 221 Jun 88

p53, a transformation-related protein located in the nucleus, shares several properties with the product of the nuclear proto-oncogene c-myc. The latter is transiently induced after different membrane-originating stimuli. A similar observation has been made with c-fos, a gene that also belongs to the 'nuclear' class of oncogenes. Here we show that p53, unlike the products of the c-myc and c-fos genes, is not induced by the signal generated by the interaction between epidermal growth factor (EGF) and its receptor. Hence, p53 does not appear to be involved in EGF signal transduction. In order to draw this conclusion we have used an EGF receptor gene-amplified human breast tumor cell line that is growth-inhibited by EGF, and exponentially growing normal human fibroblasts.
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PMID:Comparative analysis of the involvement of p53, c-myc and c-fos in epidermal growth factor-mediated signal transduction. 243 65

To address the role of c-fos proto-oncogene we constructed a plasmid that allows constitutive expression of RNA complementary to c-fos mRNA, and stably introduced this plasmid into F9 embryonal carcinoma cells. Some F9 clones expressing c-fos antisense RNA had a reduced basal level of c-fos mRNA, and were unable to induce a c-fos mRNA as well as its protein when stimulated with phorbol ester or with interferon (IFN). Nevertheless, the ability to induce major histocompatibility class I genes following IFN treatment was not impaired in these clones. Clones expressing c-fos antisense RNA grew as rapidly as control F9 cells, and underwent differentiation after retinoic acid treatment. Unexpectedly, constitutive expression of c-myc mRNA was reduced on average by 10-fold in clones expressing c-fos antisense RNA. However, expression of the p53 gene and heat shock gene hsp 70 was not affected in these clones, indicating the existence of a specific regulatory linkage between c-fos and c-myc genes. Cycloheximide treatment led to induction of a large amount of c-fos mRNA in clones expressing c-fos antisense RNA as well as in control F9 clones. The amount of c-fos antisense RNA was also increased by cycloheximide treatment. We postulate that c-fos antisense RNA blocks expression of the endogenous c-fos gene by accelerating the degradation of c-fos mRNA and that cycloheximide treatment interferes with this degradation.
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PMID:Constitutive expression of c-fos antisense RNA blocks c-fos gene induction by interferon and by phorbol ester and reduces c-myc expression in F9 embryonal carcinoma cells. 245 69

The proto-oncogenes myc, myb, and p53 produce nuclear proteins which have been implicated in the regulation of proliferation or differentiation in a number of systems. The expression of these proto-oncogenes was studied in murine erythroleukemia (MEL) cells during (i) normal replication, (ii) DMSO-induced differentiation and (iii), alpha-difluoromethylornithine (DFMO)-restricted cell division and differentiation. The RNA levels of c-myc, c-myb, and p53 were all elevated during normal cellular proliferation; only c-myc expression declined when the cells stopped dividing although the rate of transcription for the gene was unaltered. In contrast, treatment of the cells with DFMO resulted in gradual cessation of cell replication and a decrease in transcription of c-myc, c-myb and p53. When the MEL cells were induced to differentiate with dimethyl sulfoxide (DMSO), a transient reduction in c-myc and c-myb RNA levels occurred immediately prior to the G1 arrest with a concomitant decrease in transcriptional activity, while p53 mRNA production was elevated without an increase in transcription. Similar changes of the proto-oncogene levels were observed when the MEL cells were incubated with DFMO and then later induced with DMSO, a protocol which restricts differentiation of the MEL cells. From these experiments we conclude that (i) c-myc, c-myb, and p53 are regulated independently at both the transcriptional and post-transcriptional levels, (ii) DFMO inhibits MEL cell proliferation and expression of several genes, including c-myc, c-myb and p53, and (iii) DFMO suppresses terminal differentiation but is unable to alter proto-oncogene changes associated with the early stages of differentiation.
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PMID:Transcriptional and post-transcriptional regulation of c-myc, c-myb, and p53 during proliferation and differentiation of murine erythroleukemia cells treated with DFMO and DMSO. 245 48

To study the function of proto-oncogene c-fos, we prepared an antisense plasmid that expresses in mammalian cells c-fos antisense RNA which is complementary to the endogenous c-fos mRNA. Upon transfection into undifferentiated F9 EC cells, the antisense plasmid directed constitutive expression of a large amount of c-fos antisense RNA. These cells were very low in the basal level of c-fos message and were unable to induce c-fos message when stimulated with interferon or phorbol ester. The failure to induce c-fos message led to the blockade of c-fos protein expression in these cells. Thus, these cells represented a c-fos defective phenotype. The blockade of c-fos gene expression seen in antisense-cells could be caused by rapid degradation of the c-fos message, since c-fos mRNA expression was rescued in these cells when treated with protein synthesis inhibitor, cycloheximide. We found that expression of c-myc gene was down-regulated in c-fos antisense-cells: Although control undifferentiated F9 cells constitutively expressed a high level of c-myc message, the antisense cells had a much lower amount of c-myc mRNA. Since p53 and heat shock gene 70 were expressed at comparable levels in control and antisense cells, c-myc gene expression appears to be regulated by c-fos gene in F9 EC cells. Lastly, these antisense cells grew as rapidly as control F9 cells and underwent differentiation after retinoic acid treatment, indicating that c-fos expression is not a prerequisite for differentiation of F9 cells.
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PMID:c-fos antisense RNA blocks expression of c-fos gene in F9 embryonal carcinoma cells. 246 66

The papovavirus SV40 is able to induce tumours in susceptible hosts and will transform cells in vitro. Its major early protein, large T antigen, is required for viral DNA synthesis, both in vivo and in vitro, and is also responsible for the oncogenic action of the virus. We have made use of an extensive library of anti-T monoclonal antibodies to investigate the cellular effects of T. Large T shares an antigenic determinant with a growth-regulated host protein, p68, which is a member of an expanding super-family of helicases with particular homology to the translation initiation factor elF-4A. We have also studied the binding and interaction of large T with two particular host components: the replicative enzyme DNA polymerase alpha and the proto-oncogene p53. These two proteins bind to similar regions of T and exert similar effects on its antigenic structure. We found that p53 can block the binding of DNA polymerase alpha to T as well as co-existing with DNA polymerase alpha in a trimeric complex with T. This suggests that these interactions may be important in the oncogenic and replicative action of large T.
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PMID:Host proteins that bind to or mimic SV40 large T antigen: using antibodies to look at protein interactions and their significance. 247 59

DNA clones of the wild-type p53 proto-oncogene inhibit the ability of E1A plus ras or mutant p53 plus ras-activated oncogenes to transform primary rat embryo fibroblasts. The rare clones of transformed foci that result from E1A plus ras plus wild-type p53 triple transfections all contain the p53 DNA in their genome, but the great majority fail to express the p53 protein. The three cell lines derived from such foci that express p53 all produce mutant p53 proteins with properties similar or identical to transformation-activated p53 proteins. The p53 mutants selected in this fashion (transformation in vitro) resemble the p53 mutants selected in tumors (in vivo). These results suggest that the p53 proto-oncogene can act negatively to block transformation.
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PMID:The p53 proto-oncogene can act as a suppressor of transformation. 1505 86

Aberrations in nuclear proto-oncogene organisation and/or gene expression have been implicated in cell transformation mediated by the v-abl gene. For example, it has been suggested that amplification of the c-myc proto-oncogene is a co-operative event in v-abl induced fibroblast transformation. We have investigated amplification of the c-myc, p53 and c-fos nuclear proto-oncogenes in several Abelson murine leukaemia virus (A-MuLV) transformed fibroblast lines. None of these proto-oncogenes were detectably rearranged or amplified in v-abl transformed Swiss 3T3 lines. In contrast, NIH3T3 fibroblasts transformed by the v-abl gene consistently showed a 4 to 16-fold amplification of the c-myc gene. These data show that c-myc gene amplification is not an obligatory event associated with A-MuLV transformation, but may be restricted to cell lines derived from NIH3T3. c-myc gene amplification also did not correlate with a reduced latency period for tumour induction in nude mice. In addition, c-myc amplification was not selected during tumourigenesis, indicating that this event is not required for A-MuLV transformed Swiss 3T3 cells to display a full tumourigenic phenotype.
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PMID:Analysis of A-MuLV transformed fibroblast lines for amplification of the c-myc, p53 and c-fos nuclear proto-oncogenes. 254 44


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