Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using antisera to major excreted protein (MEP) of Kirsten sarcoma virus transformed NIH 3T3 (KNIH) cells, we have identified phosphoproteins from the media of feline sarcoma virus (FeSV) transformed mink cells. These secretory phosphoproteins from FeSV-transformed mink cells are of 35 kDa M.W. and they do not have autophosphorylation activity. A comparative analysis of MEP from the media of transformed mouse and mink cells was performed on the basis of proteolytic cleavage products and acid hydrolyzed products of the phosphoproteins. While a marked difference was observed in the peptide map, a common 32P-linked molecule was observed following acid hydrolysis of both species of phosphoproteins.
Cell Mol Biol 1992 Feb
PMID:Retrovirus transformation associated secretory phosphoproteins of mouse and mink cells. 155 43

The endometrial stroma plays a decisive role in sustaining the gland epithelium along the menstrual cycle, and in preparing the microenvironment that allows embryo implantation. The stroma undergoes important changes during the menstrual cycle that affects both the cell number and differentiation. These changes are regulated by both estrogen and progesterone. Stromal sarcomas are extremely rare, occurring much less than any other uterine tumor. Their origin and biology are poorly understood. The purpose of this work was to try to learn more about the stromal physiology, and also to ascertain whether the stromal sarcoma has characteristics of hormone dependence. We studied the presence of estrogen receptors (ER), progesterone receptors (PR) and the stress-responsive protein of 27K (srp27, a protein first described as an estrogen-induced 24K protein in MCF-7 cells) in both normal stroma and stromal sarcoma. The ER and PR were measured by exchange assays. The srp 27 was studied both by Western-blot and by IHC by means of specific monoclonal antibodies. The stromal sarcomas studied showed a high concentration of both ER (96 to 116 fmol/mg prot.) and PR (565 to 995 fmol/mg prot.). These amounts of ER and PR were higher than the mean found in normal endometrium during the proliferative phase (43 and 637 fmol/mg prot., respectively), and much higher than that of the secretory phase (17 and 229 fmol/mg prot., respectively). The srp27 characterized by Western-blot in both the normal stroma and stromal sarcoma was found to be similar to the srp27 of breast cancer. The IHC results showed a very low expression of srp27 in the stroma during the proliferative phase that increases when the endometrium enters the secretory phase. The low-malignancy grade stromal sarcomas showed abundant expression of srp27, but the high-malignancy grade sarcomas showed no expression of srp27. The obtained results prove the stroma capability to express the srp27. A negative correlation between malignancy of stromal tumors and srp27 expression was found. The presence of ER and PR in some stromal sarcomas proves that they have characteristics of hormone responsiveness. These findings suggest that ER and PR assays should be routinely performed in stromal sarcomas as well as in endometrial adenocarcinomas, and also that antiestrogenic drugs might be considered for the treatment of ER and PR positive stromal sarcomas.
J Steroid Biochem Mol Biol 1992 Mar
PMID:Endometrial stromal sarcoma expression of estrogen receptors, progesterone receptors and estrogen-induced srp27 (24K) suggests hormone responsiveness. 156 30

Proteins binding to the PEA3 enhancer motif (AGGAAG) activate the polyomavirus early promoter and help comprise the viral late mRNA initiator element (W. Yoo, M. E. Martin, and W. R. Folk, J. Virol. 65:5391-5400, 1991). Because many developmentally regulated cellular genes have PEA3 motifs near their promoter sequences, and because Ets family gene products activate the PEA3 motif, we have studied the expression of PEA3-binding proteins and Ets-related proteins during differentiation of F9 embryonal carcinoma cells. An approximately 91-kDa protein (PEA3-91) was identified in F9 cell nuclear extracts by UV cross-linking to a radiolabeled PEA3 oligonucleotide probe, and expression of PEA3-91 was down-regulated after differentiation of F9 cells to parietal endoderm. The c-ets-1 gene product binds to a sequence in the murine sarcoma virus long terminal repeat that is similar to the PEA3 motif (cGGAAG), but PEA3-91 was not cross-linked to this Ets-1-binding motif, nor did antiserum which recognizes murine c-ets-1 and c-ets-2 proteins have any effect on PEA3-binding activity in mobility shift assays. Furthermore, c-ets-1 mRNA was not detected in undifferentiated or differentiated F9 cells, and c-ets-2 mRNA levels remained high after differentiation. Antiserum against the Drosophila Ets-related E74A protein, however, recognized an approximately 92-kDa protein in F9 cells whose expression during differentiation varied in a manner identical to that of PEA3-91. These data suggest that PEA3-91 is not the product of the ets-1 or ets-2 genes but is likely to be the product of a murine homolog of the Drosophila E74 gene.
Mol Cell Biol 1992 May
PMID:Expression of a 91-kilodalton PEA3-binding protein is down-regulated during differentiation of F9 embryonal carcinoma cells. 156 49

A mutational analysis of the rat cytochrome c oxidase subunit IV (RCO4) promoter region revealed the presence of a major control element consisting of a tandemly repeated pair of binding sites for a nuclear factor from HeLa cells. This factor was designated NRF-2 (nuclear respiratory factor 2) because a functional recognition site was also found in the human ATP synthase beta-subunit gene. Deletion or site-directed point mutations of the NRF-2 binding sites in the RCO4 promoter resulted in substantial loss of transcriptional activity, and synthetic oligomers of the NRF-2 binding sites from both genes stimulated a heterologous promoter when cloned in cis. NRF-2 binding and transcriptional activation required a purine-rich core sequence, GGAA. This motif is characteristic of the recognition site for a family of activators referred to as ETS domain proteins because of the similarity within their DNA-binding domains to the ets-1 proto-oncogene product. NRF-2 recognized an authentic Ets-1 site within the Moloney murine sarcoma virus long terminal repeat, and this site was able to compete for NRF-2 binding to the RCO4 promoter sequence. In addition, a single polypeptide of 55 kDa was detected following cross-linking of a partially purified NRF-2 fraction to RCO4, the human ATP synthase beta subunit, or Moloney murine sarcoma virus binding sites. However, in contrast to Ets-1, which appears to be exclusive to lymphoid tissues, NRF-2 has the broad tissue distribution expected of a regulator of respiratory chain expression.
Mol Cell Biol 1991 Nov
PMID:Transcriptional activation through ETS domain binding sites in the cytochrome c oxidase subunit IV gene. 165 36

Proliferin (PLF), a protein which has homology to PRL and GH, has been implicated in the regulation of cell growth and differentiation. PLF1 was detected and found to be differentially regulated during myogenesis in the rodent myogenic cell line C2C12. Transient and stable constitutive high level expression of PLF1 repressed expression of the transfected cardiac and skeletal alpha-actin myogenic-specific promoters, but did not affect expression of the cytoskeletal beta-actin and several viral promoters linked to CAT. Stable cotransfection analyses of 5' unidirectionally deleted actin promoters and a PLF expression vector indicated that PLF exerted its effect on transcription down-stream of nucleotide positions -177 and -154 with respect to the start of transcription at 1 in the cardiac and skeletal alpha-actin promoters. Analyses of cells stably transfected with PLF showed reduced levels of MyoD mRNA, a recently identified gene that is sufficient to convert pluripotential 10T1/2 cells into myoblasts. However, transient constitutive expression of MyoD by the Moloney sarcoma virus long terminal repeat did not override the effect of PLF. Electrophoretic mobility shift analysis of nuclear extracts from C2C12 cells stably transfected with a PLF expression vector displayed drastically reduced levels or activity of the CArG-binding factor (CBF) relative to the ubiquitously expressed transcription factor Oct-1. High affinity interaction between CBF and alpha-actin promoter sequences in vitro directly correlates with functional in vivo expression. CBF is a transcription factor that is sufficient and necessary for myogenic-specific transcription, interacts with the promoter sequences targeted by PLF, and is immunologically related to the serum response factor. In conclusion, PLF selectively represses myogenic-specific transcription within the actin multigene family by suppressing the level and/or activity of a trans-acting factor (CBF) that modulates multiple muscle-specific genes. The data provide a molecular explanation for the inhibition of differentiation by an endogenously produced growth factor/hormone that is differentially expressed during myogenesis and a physiologically important antagonistic regulator of muscle-specific transcription.
Mol Endocrinol 1991 Jun
PMID:Proliferin, a prolactin/growth hormone-like peptide represses myogenic-specific transcription by the suppression of an essential serum response factor-like DNA-binding activity. 165 42

The pyruvate-stimulated adenylate cyclase from Brevibacterium liquefaciens produces up to 450 microM cyclic AMP in the culture medium when the bacterium is grown on glucose and alanine. In this paper we report the cloning, expression and sequencing of the gene for this enzyme. Residues were identified, within the C-terminal domain, which are conserved in adenylate and guanylate cyclase sequences from eukaryotes and in the adenylate cyclase of the prokaryote Rhizobium meliloti. We have also identified a sequence of 30 residues near the N-terminus of the protein which is homologous to part of the regulatory domain of the cellular homologues of the oncogenes fes and fps; this sequence is also present in the avian Fujinami sarcoma virus fps gene.
Mol Microbiol 1991 May
PMID:A pyruvate-stimulated adenylate cyclase has a sequence related to the fes/fps oncogenes and to eukaryotic cyclases. 168 68

The plant diterpene forskolin reverses acquired resistance to doxorubicin in variants of the murine sarcoma S180 cell line. Because forskolin is known to elevate intracellular cAMP levels, investigations were performed to determine whether this reversal of resistance resulted from effects on signal transduction. Two analogues of forskolin, dideoxyforskolin, which does not elevate cAMP, and a water-soluble analogue, were also investigated. Although all three diterpenes elevated levels of either cAMP or protein kinase C, these effects were not consistently associated with reversal of doxorubicin resistance. Likewise, all three diterpenes were capable of displacing [3H]azidopine from P-glycoprotein, but reversal of doxorubicin resistance was observed only with forskolin and dideoxyforskolin, suggesting that binding to P-glycoprotein may be a necessary, but not sufficient, condition for reversing doxorubicin resistance. The hydrophobicity of the compounds appeared to be the single factor most consistently related to reversal of doxorubicin resistance in this cell system, with the hydrophilic compound water-soluble forskolin failing to produce this result, even at concentrations 10-fold higher than effective concentrations of the hydrophobic diterpenes.
Mol Pharmacol 1991 Dec
PMID:Reversal of doxorubicin resistance by hydrophobic, but not hydrophilic, forskolins. 168 37

High molecular weight DNA, which was isolated from a chondrosarcoma cell line, was transfected into human neonatal foreskin fibroblasts and NIH/3T3 cells. Both types of transfected cells expressed anchorage-independent growth in soft agar and produced tumors in nude mice. The tumors which developed in nude mice following injection of transfected human fibroblasts grew to approximately 0.8 cm in diameter in four weeks. The tumors which developed from transfected NIH/3T3 cells grew to greater than 2.0 cm in diameter in 6 weeks. After growth in soft agar the transfected human fibroblasts expressed a cell surface sarcoma-associated epitope recognized by the monoclonal antibody 345.134S. In addition to the transfected human fibroblasts, the original human chondrosarcoma tumor, the chondrosarcoma cell line derived from the tumor, and the nude mouse tumor which developed from transfected human fibroblasts all exhibited positive reactivity with the monoclonal antibody 345.134S. Transfected NIH/3T3 cells that exhibited anchorage-independent growth and tumorigenicity did not exhibit detectable reactivity with the monoclonal antibody. These results suggest that the expression of the tumor-associated cell surface antigen appears to be an early event correlated with transformation of the transfected human cells but not directly related to the tumorigenic potential of the DNA. The transfected cells which expressed anchorage independent growth exhibited the sarcoma cell surface antigen prior to attaining the potential for tumorigenicity.
Exp Mol Pathol 1990 Oct
PMID:HNF transfection with chondrosarcoma DNA results in the development of a sarcoma cell surface-associated epitope. 170 62

A set of genes is rapidly inducible when quiescent fibroblasts are stimulated by growth factors or by the activation of temperature-sensitive retroviral protein-tyrosine kinases. Most of these so-called immediate-early genes were cloned by differential cDNA hybridization. DNA sequence analysis identified many of them as putative members of the growth factor or of the transcription factor gene family, suggesting a role in signal transmission during the G0-to-G1 transition. In this study, we identified one of the genes that are rapidly inducible by the retroviral protein-tyrosine kinases v-Src and v-Fps of Rous sarcoma virus and Fujinami sarcoma virus, respectively, as the rhoB gene, a member of the ras gene superfamily whose products are GTP-binding proteins, rhoB is transiently activated at the transcriptional level by v-Fps and by epidermal growth factor. Its labile RNA is inducible in the presence of cycloheximide but not of actinomycin D. rhoB is strongly induced by epidermal growth factor and by platelet-derived growth factor both in subconfluent, serum-starved and in density-arrested Rat-2 fibroblasts. Fetal calf serum is a poor inducer, particularly in density-arrested cells, and phorbol esters do not increase rhoB expression at all. These data suggest that rhoB is inducible by protein-tyrosine kinases through a pathway not involving the activation of protein kinase C. Neither the closely related rhoC and rhoA genes nor the distantly related c-H-ras gene is rapidly inducible by mitogens. Thus, rhoB is the first known member of the small GTP-binding proteins among the immediate-early genes.
Mol Cell Biol 1991 Jul
PMID:The ras-related gene rhoB is an immediate-early gene inducible by v-Fps, epidermal growth factor, and platelet-derived growth factor in rat fibroblasts. 171 Jul 70

A methylcholanthrene-induced rat sarcoma that can be propagated in vitro or in vivo was evaluated for resistance to antifolates and was found to be relatively resistant to methotrexate and 10-ethyl-10-deazaaminopterin but sensitive to trimetrexate. Rat sarcoma cell extracts contained low levels of dihydrofolate reductase activity, the target enzyme of methotrexate, and inhibition of this enzyme by these three antifolates was similar. Transport studies showed poor uptake of both methotrexate and 10-ethyl-10-deazaaminopterin. In contrast, trimetrexate achieved high intracellular levels. The poor uptake of methotrexate was not due to lack of polyglutamylation. Thus, the basis for natural resistance to methotrexate and 10-ethyl-10-deazaaminopterin, compared with trimetrexate, in this rat sarcoma cell line was due to decreased transport of these drugs.
Mol Pharmacol 1991 Nov
PMID:Mechanisms of sensitivity and natural resistance to antifolates in a methylcholanthrene-induced rat sarcoma. 171 70


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