Rous sarcoma virus discovery

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. 

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. 

The first virus linked to tumor production was discovered in 1908 by Ellerman and Bang. Their finding was followed in 1911 by the better known discovery by Peyton Rous of a virus that produces sarcomas in chickens (now known as Rous sarcoma virus, or RSV). Later (1932) Shope showed that a papilloma virus produced cutaneous tumors in rabbits, and Lucke (1934) showed that adenoviruses produced renal adenocarcinoma in the frog. These and other discoveries made in the 1940s and 1950s indicated that exposure to certain viruses could result in tumor production. However, viral oncogenes had not yet been identified, and skeptics... 

It is now almost exactly 50 years since I went as a postdoctoral fellow learn about cell culture in Harry Rubin s group in the Virus Laboratory at the University of California at Berkeley. The use of cell cultures had created the breakthroughs in quantitative animal virology, which led, inter alia, to the production of polio vaccines (albeit at the cost of the lives of hundreds of thousands of rhesus monkeys, whose kidney cells were used to produce the viruses for the vaccines). We worked on Rous sarcoma virus (RSV) and chicken leucosis viruses in chick embryo fibroblast cell cultures. Rubin and Temin had developed an assay for RSV, based on the production of foci of virus-transformed fibroblasts, and Temin did the crucial experiments which showed that RSV, an RNA virus, made a DNA copy of itself, which was used to produce new virus particles. The enzyme involved was reverse transcriptase, and its discovery was one of the most important leaps forward in cell and molecular biology. 

Herbimycin was found to have potent herbicidal activity against most mono- and dicotyledonous plants, especially against Cyperus microiria STEUD but strong resistance by Oryza saliva [173]. It was also reported that herbimycins showed cytocidal activity on both HeLa cells and Ehrlich cells in vitro and could convert the transformed morphology of Rous sarcoma virus-infected rat kidney cells to the normal ones [177]. However, interest in geldanamycin and herbimycin increased greatly upon the discovery of their potent antitumor activity at nanomolar concentrations [178, 179]. 

The first evidence for a tumour-inducing virus was from sarcomas in domestic fowl. Rous discovered in 1907 that a cell-fi"ee extract prepared from the minced extract of a sarcoma found in a Plymouth Rock caused sarcomas when injected into other domestic fowl. He postulated that the tumour was transmitted by a virus. The discovery received little attention then since it did not fit with the generally held theories of cancer at that time. Many years later, when a number of oncogenic viruses had been identified, the importance of Rous early discovery became apparent. Rous was awarded the Nobel prize... 

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