Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The c-fos gene, the cellular homologue of the transforming gene of the FBJ osteosarcoma virus, v-fos, is strongly induced in quiescent BALB/c 3T3 cells by growth factors and in other cell types by a wide variety of transmembrane signalling agents. c-fos is a member of a family of structurally related proteins which includes the fos-related antigens (fra). We have studied the dynamic state of the c-fos protein with an antibody prepared by immunizing rabbits with a plasmid-encoded fos fusion protein. In serum-stimulated BALB/c 3T3 cells, the antibody recognizes a nuclear antigen which resolves on SDS-PAGE as a 60-68-kD group of bands corresponding to c-fos, a doublet at 44-45-kD corresponding to the noncovalently associated p39 protein, as well as an approximately 50-kD band corresponding to a fra. We show that although c-fos protein synthesis is only transiently induced by serum, the c-fos protein persists within the cell after its synthesis has ceased, and it decays with a half-life of 2 hours. Significantly, newly synthesized p39 continues to appear in the immune-precipitated complex even at times when c-fos is no longer synthesized. These kinetics indicate that even following shutoff of c-fos protein synthesis, p39 is newly synthesized and can complex with c-fos protein or a fos-related antigen. During this time, c-fos also undergoes an extensive posttranslational modification. The modification is partially reversed by phosphatase treatment, which implicates protein phosphorylation. Together these results suggest that both interaction with p39 and phosphorylation may progressively modify the properties of c-fos and/or the fos-related antigens over a period of 4-8 hours following the shutoff of fos synthesis. We discuss the implications of the dynamic state of c-fos and fra protein interactions for the function of these proteins.
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PMID:Dynamic interactions of c-fos protein in serum-stimulated 3T3 cells. 249 95

The transforming gene of the osteosarcoma-producing FBJ murine sarcoma virus, v-fos, is homologous to a normal cellular gene, c-fos, in vertebrate species. Transcripts from the c-fos proto-oncogene accumulate to very high levels in late gestational mouse and human extra-embryonic tissues. We now report that these RNA transcripts are translated in these tissues. Rabbits were immunized with a synthetic peptide whose sequence is common to both c-fos and v-fos. After affinity purification on an immunosorbent containing the fos peptide (a nonapeptide), the antibody reacted with a component(s) in nuclei in sections of human and murine tissues and immunoprecipitated the v-fos gene product (p55) and a cellular protein of 39 kd (p39, complexed with fos) from lysates of metabolically-labelled virally transformed cells. Crude extracts of normal tissues contained major anti-fos-reactive proteins in the range of 55-60 kd as shown by protein blot analysis. Indirect immunofluorescence and immunoperoxidase staining showed that in addition to strong immunoreactive component(s) in the nuclei of extra-embryonic tissues of human and mouse, weaker reactions are detectable in all normal fetal and adult tissues tested. This demonstrates that fos-reactive protein is expressed in a wide variety of cells and tissues.
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PMID:Product of the cellular oncogene, c-fos, observed in mouse and human tissues using an antibody to a synthetic peptide. 389 12

Sera from rat bearing tumors induced by inoculation of FBJ murine osteogenic sarcoma virus (FBJ-MSV) nonproducer rat cells precipitate two proteins with molecular weights of 55,000 (p55) and 39,000 (p39) from FBJ-MSV-transformed cells. These proteins cannot be precipitated from uninfected cells or cells transformed by other strains of murine sarcoma virus, nor can they be precipitated by sera specific for the viral structural proteins. A methionine tryptic peptide mapping analysis showed that p55 and p39 have little or no homology and that they are not related to the helper virus gag and env gene products. p55 could also be detected among the in vitro translation products of 70S RNA from FBJ murine leukemia virus plus FBJ-MSV virions but not among those from FBJ murine leukemia virus alone. This suggests that p55 is encoded by the FBJ-MSV genome, whereas p39, which was not detected among the in vitro translation products, may not be virus encoded. Another difference between p55 and p39 is that p55 is phosphorylated, with most of the phosphate on a serine residue(s), whereas p39 is phosphorylated to a much lesser extent, if at all. No protein kinase activity was associated with p55 and p39 immune complexes under standard conditions. Our data suggest that p55 is a strong candidate for the FBJ-MSV oncogene product.
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PMID:Candidate product of the FBJ murine osteosarcoma virus oncogene: characterization of a 55,000-dalton phosphoprotein. 628 32

A 12.0-kilobase EcoRI restriction fragment containing FBJ murine osteosarcoma virus (FBJ-MSV) proviral DNA was identified in FBJ-MSV-transformed nonproducer rat cells and molecularly cloned in bacteriophage Charon 30 (lambda FBJ-1). A 5.8-kb HindIII fragment containing the entire FBJ-MSV proviral DNA was isolated from lambda FBJ-1 and subsequently subcloned in plasmid pBR322 (pFBJ-2). The DNA from recombinant plasmid pFBJ-2 was able to induce morphological transformation of rat fibroblasts in tissue culture. Transfected cells contained the p55 and p39 antigens specific for cells transformed by FBJ-MSV (T. Curran and N. M. Teich, J. Virol. 42:114-122, 1982). The organization of the FBJ-MSV provirus was analyzed by restriction endonuclease mapping, and a region of nonhomology with the helper virus was delineated. Sequences specific for this region (presumably the viral fos gene) were subcloned and used as a probe to identify related sequences present in the normal genomes of cells from a variety of mammalian species (cellular fos). A single-size (3.4 kilobases long) class of RNA hybridizing to the viral fos probe was identified in FBJ-MSV-transformed cells.
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PMID:FBJ murine osteosarcoma virus: identification and molecular cloning of biologically active proviral DNA. 629 25

The retinoblastoma tumor suppressor gene (RB-1) is a key regulator of cellular senescence. Expression of the retinoblastoma protein (pRB) in human tumor cells that lack it results in senescence-like changes. The induction of the senescent phenotype by pRB requires the postmitotic kinase CDK5, the best known function of which is in neuronal development and postmitotic neuronal activities. Activation of CDK5 in neurons depends on its activators p35 and p39; however, little is known about how CDK5 is activated in non-neuronal senescent cells. Here we report that p35 is required for the activation of CDK5 in the process of cellular senescence. We demonstrate that: (i) p35 is expressed in osteosarcoma cells, (ii) p35 is required for CDK5 activation induced by pRB during senescence, (iii) p35 is required for the senescent morphological changes in which CDK5 is known to be involved as well as for expression of the senescence secretome, and (iv) p35 is up-regulated in senescing cells. Taken together, these results suggest that p35 is at least one of the activators of CDK5 that is mobilized in the process of cellular senescence, which may provide insight into cancer cell proliferation and future cancer therapeutics.
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PMID:p35 is required for CDK5 activation in cellular senescence. 2018 42