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U R Rapp

Publications and source records attributed to U R Rapp.

224 records · Page 13Linked to original sources
PubMed1978

Acquisition of oncogenicity by endogenous mouse type C viruses: effects of variations in env and gag genes.

Several dual-tropic isolates derived from the thymuses of preleukemic or leukemic AKR mice and a more recrnt group of viruses generated by in vitro or in vivo passage of a poorly infectious endogenous virus of C3H mouse cells have been shown to be highly oncogenic. By analysis of the immunological properties of their gag gene-coded structural proteins, each of the AKR-derived isolates and two dual-tropic C3H-derived isolates were found to closely resemble AKR murine leukemia virus. In contrast, gag gene-coded proteins of two other leukemogenic isolates of C3H origin, including one ecotropic and one dual-tropic virus, were indistinguishable from those of Moloney murine leukemia virus. All of the oncogenic isolates, including those of AKR and C3H origin, were found to possess common envelope glycoprotein determinants of a unique class not shared by the nononcogenic ecotropic viruses from which they were derived. These findings support the possibility that oncogenic variants of endogenous ecotropic mouse type C viruses are derived by genetic recombination. This recombinational event appears to involve the acquisition, by different ecotropic viruses, of a common class of endogenous virus-coded envelope glycoprotein determinants which are presumably required, but not necessarily sufficient, for oncogenicity.

AKR murine leukemia virus↗
PubMed1976

Endogenous ecotropic mouse type C viruses deficient in replication and production of XC plaques.

Endogenous ecotropic type C viruses were induced by iodedeoxyuridine from nontransformed and chemically or spontaneously transformed clones of the C3H/10T1/2 cell line. Viruses produced by cells of certain transformed clones were N-tropic and formed large XC plaques. In contrast, viruses produced by nontransformed C3H/10T1/2 cells were not detectable in the XC plaque test. These XC- viruses infected mouse cells with high efficiency, as shown by the induction of murine leukemia virus group-specific antigens in infected cells, but virus production, as determined by DNA polymerase-containing particles, was extremely low. Upon growth in certain mouse cells these replication-deficient, XC(-) viruses converted to type C viruses that were similar in XC assays to N-tropic AKR virus (XC+).

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PubMedDate not supplied

Homologous cell-derived oncogenes in avian carcinoma virus MH2 and murine sarcoma virus 3611.

Retroviral oncogenes (v-onc) are derived from cellular genes (c-onc) which are highly conserved among different species. Retrovirus-transduced oncogenes are most commonly associated with the induction of haematopoietic tumours and sarcomas. The avian retrovirus Mill Hill no. 2 (MH2) was isolated from a spontaneous ovarian tumour of a chicken and is distinguished by the predominant induction of liver and kidney carcinomas in fowl. MH2 also induces transformation of fibroblasts, macrophages and epithelial cells in culture. The genome of MH2 contains two unrelated and independently expressed cell-derived oncogenes, v-mil and v-myc. Three other viral isolates among avian acute transforming retroviruses contain the v-myc oncogene, but only MH2 contains both v-myc and v-mil. Hence, some of the pathogenic specificities of MH2 may be due to the simultaneous expression of two oncogenes. The murine sarcoma virus 3611 (3611-MSV) isolated from a mouse carrying lung carcinoma and peritoneal tumours, induces fibrosarcomas in newborn mice and the transformation of fibroblasts and epithelial cells in culture. The oncogenic properties of 3611-MSV are due to the presence in its genome of a cell-derived oncogene termed v-raf. We report here that the two independently transduced oncogenes v-mil and v-raf are closely related and that they were apparently derived from homologous cellular genes of avian and mammalian species.

Animals↗
PubMedDate not supplied

Nucleotide sequence of avian retroviral oncogene v-mil: homologue of murine retroviral oncogene v-raf.

Eukaryotic cells contain genes termed proto-oncogenes (c-onc) which have the potential to transform cells in culture and induce tumours in vivo. Most of these genes have been identified by their occasional incorporation into retroviral genomes which can act as natural transducing vectors for these and perhaps other cellular genes. Cell-derived oncogenes of retroviruses (v-onc) are associated mostly with the induction of mesenchymal tumours whereas carcinoma induction is rare. One of these rare carcinoma-inducing viruses is the acutely transforming avian retrovirus MH2 (refs 3-5). Recently we and others have shown that this virus carries a novel putative oncogene, v- mil , in addition to the known oncogene v-myc. While the transforming ability of v- mil has not been directly established, we have recently discovered by hybridization analysis that v- mil is homologous to v-raf (ref. 9), the transforming gene of the murine retrovirus 3611 MSV (ref. 10). Both viruses express the mil /raf oncogene product as a gag-fusion polyprotein, while the myc oncogene of MH2 is expressed via a subgenomic mRNA. Here we report the complete nucleotide sequence of v- mil and compare it with that of v-raf. The 80% homology between the nucleotide sequences and the 94% homology between the predicted amino acid sequences of the two viral genes clearly indicate that these are the avian and murine forms of the same gene. Comparison of the two sequences with that of the human cellular homologue (T. I. Bonner et al., manuscript in preparation) indicates that v-raf has more 3' untranslated sequences while v- mil has additional sequences from two 5' exons of the cellular homologue. Although the mil /raf amino acid sequences reveal partial homology to that of the v-src product, no tyrosine-specific protein kinase activity is detected for the gag- mil and the gag-raf hybrid proteins.

Amino Acid Sequence↗
PubMedDate not supplied

Serine- and threonine-specific protein kinase activities of purified gag-mil and gag-raf proteins.

Retroviruses carry cell-derived oncogenes (v-onc) that have the potential to transform cells in culture and induce tumours in vivo. One of the few carcinoma-inducing viruses is the acutely transforming retrovirus MH2, which carries the putative oncogene v-mil and the known oncogene v-myc. Recently, a high degree of homology was discovered between v-mil and v-raf, the transforming gene of the murine retrovirus 3611 murine sarcoma virus (MSV), whereas homology to v-src is low. Both viruses express their oncogenes as the gag-fusion polyproteins p100gag-mil and p75gag-raf (of respective relative molecular mass (Mr) 100,000 and 75,000), while the myc oncogene of MH2 is expressed by means of a subgenomic messenger RNA. We have recently demonstrated that p100gag-mil is not a nuclear protein. Here we report that purified p100gag-mil and p75gag-raf exhibit protein kinase activities in vitro which, in contrast to the src-related p130gag-fps of Fujinami sarcoma virus (FSV) and all other characterized oncogene-encoded protein kinases, phosphorylate serine and threonine but not tyrosine. Both types of protein kinases phosphorylate lipids in vitro.

Animals↗
PubMedDate not supplied

Abrogation of IL-3 and IL-2 dependence by recombinant murine retroviruses expressing v-myc oncogenes.

Several oncogenes are thought to cause transformation by affecting the signal transmission pathway of growth factors. One example is the induction of c-myc, the cellular homologue of the avian transforming oncogene v-myc, by platelet-derived growth factor (PDGF) among a set of genes associated with competence induction in fibroblasts. Another of the competence genes, r-fos, has been shown to be related to v-fos, the transforming gene of the FBJ sarcoma virus. In addition, PDGF induces c-fos, the cellular homologue of v-fos. The importance of c-myc induction is suggested by the observation that c-myc, under the control of a glucocorticoid regulator, can partially relieve the requirement of fibroblasts for PDGF. We have examined the effects of oncogenes on haematopoietic/lymphoid cell differentiation, immortalization and factor dependence for growth. Here we report the effects of recombinant murine retroviruses capable of expressing the avian v-myc. With interleukin-3 (IL-3)- or interleukin-2 (IL-2)-dependent cells, the viruses abrogated the requirement for growth factors and suppressed c-myc expression.

Animals↗
PubMedDate not supplied

Selective immortalization of murine macrophages from fresh bone marrow by a raf/myc recombinant murine retrovirus.

Myeloid precursors can be grown in vitro in the presence of specific growth factors; however, their expansion is limited by a competing process of terminal differentiation. Proto-oncogenes seem to be involved in cellular proliferation and/or differentiation and may also play a role in the myelopoietic process. Murine myeloid precursors which are grown in vitro with growth factors respond with augmented self-renewal upon infection with recombinant retroviruses carrying the v-myc or v-src oncogenes, suggesting a synergism or complementation between some viral oncogenes (v-onc) and certain growth factors. We now show that the combination of two v-onc genes (raf and myc) induces the selective proliferation of monocytic cells from fresh murine bone marrow (BM) in the absence of a specific growth factor supplement. Depending on the culture conditions these cells can either differentiate and cease to proliferate or grow continuously, thus mimicking the alternative pathways that can be followed by committed BM stem cells in vivo.

Animals↗