HA-RAS IN NORMAL AND TUMORAL TISSUES - STRUCTURE, FUNCTION AND REGULATION

The c-Ha-ras1 gene belongs to an eucaryotic ubiquitous gene family whi ch codes important molecules involved in the transduction of mitogenic signals and of cellular differentiation. The c-Ha-ras1 estructure, in four coding exons and a non-coding 5'exon, is highly preserved throug hout evolution. This gene, which generates a 1.4 Kb transcript, is exp ressed in practically all the cell lineages with a tissue-specific pat tern. The coded protein, of 189 amino acids and 21 kDa, is a small pr otein that binds guanine nucleotides (GTP/GDP), is associated with the plasma membrane and possesses low intrinsic GTPase activity. p21ras f unctions as a molecular switch active when GTP is bound to it and inac tive in the GDP-bound form. Its activity is very tightly controlled in the cell by various positive and negative control mechanisms. The ras gene family is the most frequently involved in the development of hum an and animal tumors. Qualitative (point mutations) and quantitative ( over expression) mechanisms of oncogenic activation have been describe d. The possible relation between determined human Ha-ras1 alleles and the predisposition to cancer has been suggested as well.