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 The Ras-association domain family (RASSF) members and their role in human  tumourigenesis van der Weyden L; Adams DJBiochim Biophys Acta  2007[Sep]; 1776 (1): 58-85Ras proteins play a direct causal role in human cancer with activating mutations  in Ras occurring in approximately 30% of tumours. Ras effectors also contribute  to cancer, as mutations occur in Ras effectors, notably B-Raf and PI3-K, and  drugs blocking elements of these pathways are in clinical development. In 2000, a  new Ras effector was identified, RAS-association domain family 1 (RASSF1), and  expression of the RASSF1A isoform of this gene is silenced in tumours by  methylation of its promoter. Since methylation is reversible and demethylating  agents are currently being used in clinical trials, detection of RASSF1A  silencing by promoter hypermethylation has potential clinical uses in cancer  diagnosis, prognosis and treatment. RASSF1A belongs to a new family of RAS  effectors, of which there are currently 8 members (RASSF1-8). RASSF1-6 each  contain a variable N-terminal segment followed by a Ras-association (RA) domain  of the Ral-GDS/AF6 type, and a specialised coiled-coil structure known as a SARAH  domain extending to the C-terminus. RASSF7-8 contain an N-terminal RA domain and  a variable C-terminus. Members of the RASSF family are thought to function as  tumour suppressors by regulating the cell cycle and apoptosis. This review will  summarise our current knowledge of each member of the RASSF family and in  particular what role they play in tumourigenesis, with a special focus on  RASSF1A, whose promoter methylation is one of the most frequent alterations found  in human tumours.|*Gene Expression Regulation, Neoplastic[MESH]|Animals[MESH]|DNA Methylation[MESH]|Gene Silencing[MESH]|Genes, ras/*physiology[MESH]|Humans[MESH]|Neoplasms/genetics/*pathology[MESH]|Tumor Suppressor Proteins/*physiology[MESH]
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