In Rous sarcoma

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). 

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

Most of oncogene products that are protein kinases phosphorylate specific tyrosine residues. Examples of these are src, fps, yes and sea. RSVsrc, which occurs in Rous sarcoma virus, has been the most studied. The gene products of src, fps and yes are peripheral membrane proteins associated with the cytoplasmic surface of the plasmalemma (Fig. 11.5). Both p60 " and p60 possess specific tyrosine kinase activity but with an important functional difference, namely, that p60 " kinase activity is regulated through normal cellular mechanisms and does not transform cells, whereas kinase is readily activated and... 

What signals would cause the 4OS subunit to arrest at the correct initiation site in normal circumstances In the vast majority of mRNAs examined the initiation site is the 5 proximal AUG codon ( 2), but there are hints that this is not so absolutely universal that it could be the sole criterion for initiation site selection. For example, in Rous Sarcoma Virus RNA it is the second AUG codon from the 5 end that is thought to be the site of initiation of translation (79) 1 this is substantiated the... 

J. Arango, M. Pierce, Comparison of N-acetylg ucosaminyltransferase V activities in Rous Sarcoma-transformed baby hamster kidney (RS-BHK) and BHK cells, J Cell Biochem, 1988, 37, 225-231. 

Cell-surface structure and function in Rous sarcoma virus-transformed cells, in Biogenesis and Turnover of Membrane Macromolecules (J. S. Cook, ed.), pp. 251-276, Raven Press, New York. 

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)... 

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... 

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. 

Although inactive against the Rous sarcoma in the standard post-infection test, 6-mercaptopurine, 2-aminoadenine, and 8-azaguanine inhibited the development of the tumour if given prior to infection of the chicks (417, 418]. 

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. 

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... 

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]. 

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