Viruses Rous sarcoma virus

Type D (squirrel monkey retrovirus). ALV-related virus (avian leukemia virus, rous sarcoma virus). 

LDL receptor (LDLR) LDL, apo-E, hepatitis C virus, Rous sarcoma virus subgroup A, human rhinovirus Ubiquitously expressed... 

In contrast to the effects obtained with viruses mentioned earlier, rous sarcoma virus (RSV) is inactivated by direct contact with 2 [81]. Evidence for the drug action by a chelate compound was obtained by using concentrations of 3a and copper(II) sulfate, neither of which individually affected enzyme activity or transforming abilities [82]. In a later study these workers showed that several metal complexes inhibit the RNA dependent DNA polymerases and the transforming ability of RSV, the most active compound being a 1 1 copper(II)... 

ROP Retinopathy of prematurity ROS Reactive oxygen species R-PIA R-(l-methyl-I-phenyltheyl)-adenosine RPMI 1640 Roswell Park Memorial Institute 1640 medium RS Reiter s syndrome RSV Rous sarcoma virus RTE Rabbit tubular epithelium RTE-a-5 Rat tubular epithelium ant n a-5... 

FIGURE 8.13 Nonreceptor PTKs. These protein kinases form a large family, and most of them contain SH2 and SH3 domains. Several were originally discovered as transforming genes of a viral genome, hence names such as src or abl, derived from Rous sarcoma virus or Abelson murine leukemia virus, respectively. (Adapted from Hunter, T., Biochem. Soc. Trans., 24(2), 307-327, 1996.)... 

This enzyme is associated with the virions of RNA tumor viruses such as the Rous sarcoma virus (RSV). The enzyme has remarkable enzymatic activity in that it can catalyze several seemingly diverse steps in the synthesis of double-stranded DNA from the single-stranded RNA viral genome. The enzyme uses a tRNA for tryp-tophan as a primer to make a copy of DNA that is complementary to the viral RNA. The resulting RNA-DNA hybrid is converted to a double-stranded DNA molecule by ribon-uclease (RNase)H and DNA-dependent DNA polymerase activities that are intrinsic to reverse transcriptase. 

Certain RNA viruses, particularly retroviruses, have also proven capable of inducing cancer. Retroviruses known to induce cancer in animals include Rous sarcoma virus, Kirsten murine... 

J. R. Glenney Jr. and D. Soppet. Sequence and expression of caveolin, a protein component of caveolae plasma membrane domains phosphorylated on tyrosine in Rous sarcoma virus-transformed fibroblasts. Proc. Natl. Acad. Sci. USA 89 10517— 10521 (1992). 

J. R. Glenney Jr. Tyrosine phosphorylation of a 22-kDa protein is correlated with transformation by Rous sarcoma virus. J. Biol. Chem. 264 20163-20166 (1989). 

Sefton BM, Hunter T, Beemon K. 1980. Temperature-sensitive transformation by Rous sarcoma virus and temperature-sensitive protein kinase activity. J Virol 33 220-229. 

It is important to highlight that c-Src or cellular Src behaves as described above however there is a second form of Src termed v-Src or viral Src. v-Src was originally discovered as a component of the Rous Sarcoma virus, which causes cancer in chickens. The sequences of c-Src and v-Src are nearly identical. The major difference in the two proteins occurs in the C-terminal tail. While c-Src is regulated through phosphorylation of the C-terminus, v-Src has no C-terminal phosphorylation site and therefore is constitutively active and unregulated. 

Following identihcation of the Rous sarcoma virus, a substantial number of additional tumor-causing (oncogenic) viruses have been identified. We are left with the key question of how to reconcile two observations on the one hand, chemicals or chemical substances cause cancer, on the other hand, viruses cause cancer. These observations split the oncology community into two camps. As frequently happens in science, neither camp had the full story and the two opposing viewpoints proved to be entirely compatible. 

Vedel, M., Lawrence, F., Robert-Gero, M. and Lederer, E. (1978) The antifungal antibiotic sinefungin as a very active inhibitor of mefhyltransferases and of the transformation of chick embryo fibroblasts by Rous sarcoma virus. Biochemical and Biophysical Research Communications, 85, 371-376. 

Certain RNA viruses, particularly retroviruses, have also proven capable of inducing cancer. Retroviruses known to induce cancer in animals include Rous sarcoma virus, Kirsten murine sarcoma virus, avian myelocytomatosis virus, as well as various murine leukaemia viruses. Thus far, the only well-characterized human RNA transforming virus is that of human T cell lymphocytotropic virus-1 (HTLV-1), which can induce adult T cell leukaemia/lymphoma (ATL). Identification of antigens uniquely associated with various tumour types, and identification of additional cancer-causing viruses, remain areas of very active research. 

In particular cases where small amounts of myristoylated peptides are required, enzymatic N-myristoylation of unprotected and purified peptides can be achieved using the yeast TV-myristoyltransferase. This procedure has been applied for N-myristoylation of the N-terminal deca-, dodeca-, and tetradecamer fragment of pp60vsrc, the transforming protein of Rous sarcoma virus. 31 This method is particularly useful when [3H]-labeled myristoylated compounds are required. 

In comparison to the level of cellular serine or threonine phosphorylation, protein tyrosine phosphorylation occurs at quite low levels in normal cells but dramatically increases upon oncogenic transformation or stimulation. Since the first discovery in 1978 that the transforming protein from Rous sarcoma virus (pp60vsrc) exhibited intrinsic kinase activity/5 protein kinase activity has also been shown to be inherent to other growth factor receptors such as epidermal growth factor receptor and the insulin receptor,[6 91 and to involve autophosphorylation processes. The diverse biochemical activity exhibited by protein tyrosine phosphorylation has stimulated the development of chemical methods for the preparation of phosphorylated peptides for use as substrates in elucidating the biochemical and physiological activity of phosphorylated site(s). 

Some representatives of the retroviruses cause tumors in animals such as mice or chickens. The discovery of oncogenes initiated from the src gene of Rous sarcoma virus, which could be identified as the tumor causing principle of this retrovirus. The src gene codes for the Src tyrosine kinase (see 8.3). The gene sections of retroviruses responsible for tumor formation were designated oncogenes. 

Cerulenin inhibits formation of polyisoprenol, probably by uncom-petitively inhibiting HMG-CoA synthetase.250 It strongly inhibited production of Rous-sarcoma virus by infected, chick-embryo cells, but an effect on the viral glycoproteins was not observed.251 Other effects of cerulenin, such as its inhibition of fatty acid synthesis, may have caused inhibition of virus production. The inhibition, by cerulenin, of secretion of proteins by bacilli has been noted for some time, but no satisfactory explanation has as yet been offered (see Ref. 252, and ref-... 

In the presence of tunieamycin, cells infected with Rous sarcoma virus produced virus particles that lacked infectivity, and were devoid of the envelope glycoproteins gp85 and gp35. Virus particles lacking envelope glycoproteins had previously been found in a deletion mutant of Rous sarcoma virus and in a temperature-sensitive mutant of... 

The fact that earlier investigations of the effect of tunicamycin on the replication of Rous sarcoma virus failed to show the unglvcosyl-... 

Azarnia R, Loewenstein WR Intercellular communication and the control of growth. X. Alteration of junctional permeability by the sre gene. A study with temperature-sensitive mutant Rous sarcoma virus. J Membr Biol 1984 82 191-205. 

Crow DS, Beyer EC, Paul DL, Kobe SS, Lau AF Phosphorylation of connexin43 gap junction protein in uninfected and Rous sarcoma virus-transformed mamalian fibroblasts. Mol Cell Biol 1990 10 ... 

In the structure of the apo-form of HIV PR, the flaps from both monomers are related by crystallographic two-fold symmetry and can be considered as being in an open conformation. In the structures of related proteases from Rous Sarcoma Virus and HIV-2, the flaps are either crystallographically disordered or in a partly closed conformation [18]. This suggests that, in solution, in the absence of ligands, the flaps are rather flexible and that the stable conformation of the flaps observed in the crystal structure of the apo-enzyme of HIV PR could be considered to result from kinetic trapping during the crystallization process. 

Several lines of evidence demonstrate that the active unit of integrase is a multimer. It is clear, as an isolated protein in solution, that integrase forms dimers [6,10-12], and it has been shown by sedimentation equilibrium studies that Rous sarcoma virus (RS V) integrase exists in reversible equilibrium between monomeric, dimeric, and tetrameric forms [13]. Protein-protein cross-linking studies of HIV-1 [14] and RSV [15] integrases confirm the existence of protein dimers and tetramers in solution, and in vivo, the yeast GAL4 two-hybrid system has demonstrated that HIV-1 integrase can interact with itself [16]. 

Bushman FD, Wang B. Rous sarcoma virus integrase protein Mapping functions for catalysis and substrate binding. J Virol 1994 68 2215-2223. 

Retroviruses have featured prominently in recent advances in the molecular understanding of cancer. Most retroviruses do not kill their host cells but remain integrated in the cellular DNA, replicating when the cell divides. Some retroviruses, classified as RNA tumor viruses, contain an oncogene that can cause the cell to grow abnormally (see Fig. 12-47). The first retrovirus of this type to be studied was the Rous sarcoma virus (also called avian sarcoma virus Fig. 26-31), named for F. Peyton Rous, who studied chicken tumors now known to be caused by this virus. Since the initial discovery of oncogenes by Flarold Varmus and Michael Bishop, many dozens of such genes have been found in retroviruses. 

One of the best-documented examples occurs in translation of the mRNA for the overlapping gag and pol genes of the Rous sarcoma virus (see Fig. 26-31). The reading frame for pol is offset to the left by one base pair (—1 reading frame) relative to the reading frame for gag (Fig. 1). 

FIGURE 1 The gag-pol overlap region in Rous sarcoma virus RNA. 

The Rous sarcoma virus oncogene v-src and a family of related oncogenes are derived from protein tyrosine kinases that are attached with the aid of a... 

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