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Arch Hellen Med, 34(4), July-August 2017, 439-447


Flashback in the history of Ras research

G. Chaldaiopoulou, M. Goulielmaki, N. Khoury, V. Zoumpourlis
Unit of Biomedical Applications, Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, Athens, Greece

The ability of a group of retroviruses to produce tumors in infected animals was the first indication of the existence of genetic elements with oncogenic properties. After comprehensive studies on these retroviruses, the first Ras genes were identified, which were later found to be present in the rat genome. The trigger for further studies was given by the discovery of mutated Ras genes in human cancer cells. In the following years, a series of biochemical and structural, in vivo and in vitro, studies were conducted that contributed fundamental information to the field of cell and cancer biology. Ras proteins constitute a very small part of a superfamily of Ras-related small GTPases, which appear to be the main regulators of the majority of crucial cell functions. The study of these proteins has contributed to the comprehension of the molecular mechanisms involved in cancer incidence and progression, and the complex mechanisms of signal transduction in general. Through these years of in-depth investigation, the vital role of the small GTPases in biology was revealed and it became clear that extracellular signals are capable of modifying the regulation of intracellular procedures. Taking advantage of the knowledge that has been accumulated, research is now focused on finding new, effective anticancer treatments, although further investigation of the Ras genes continues to be mandatory for substantial understanding of their dynamic. This review provides a chronological flashback in the history of Ras research. A thorough analysis of the key discoveries related to the structure, biochemistry and mechanism of function of the Ras superfamily of proteins is presented, and their correlation with human cancer is highlighted.

Key words: Ras, Ras targeted cancer therapy, Ras transmission signals, Small GTPases.

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