RASSF2 is a novel K-Ras-specific effector and potential tumor suppressor.
Ras proteins regulate a wide range of biological processes by interacting with a broad assortment of effector proteins. Although activated forms of Ras are frequently associated with oncogenesis, they may also provoke growth-antagonistic effects. These include senescence, cell cycle arrest, differentiation, and apoptosis. The mechanisms that underlie these growth-inhibitory activities are relatively poorly understood. Recently, two related novel Ras effectors, NORE1 and RASSF1, have been identified as mediators of apoptosis and cell cycle arrest. Both of these proteins exhibit many of the properties normally associated with tumor suppressors. We now identify a novel third member of this family, designated RASSF2. RASSF2 binds directly to K-Ras in a GTP-dependent manner via the Ras effector domain. However, RASSF2 only weakly interacts with H-Ras. Moreover, RASSF2 promotes apoptosis and cell cycle arrest and is frequently down-regulated in lung tumor cell lines. Thus, we identify RASSF2 as a new member of the RASSF1 family of Ras effectors/tumor suppressors that exhibits a specificity for interacting with K-Ras.
Department of Cell and Cancer Biology, NCI, National Institutes of Health, Rockville, Maryland 20850-3300, USA.
Michele D
MD
Vos
Chad A
CA
Ellis
Candice
C
Elam
Aylin S
AS
Ulku
Barbara J
BJ
Taylor
Geoffrey J
GJ
Clark
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D019556:COS Cells; D016923:Cell Death; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D002469:Cell Separation; D016922:Cellular Senescence; D004247:DNA / Q000378:metabolism; D015536:Down-Regulation; D005434:Flow Cytometry; D016147:Genes, Tumor Suppressor; D005982:Glutathione Transferase / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014162:Transfection; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D018631:ras Proteins / Q000378:metabolism*
D011506:Proteins; C425300:RASSF2 protein, human; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; D006160:Guanosine Triphosphate; D004247:DNA; D005982:Glutathione Transferase; D018631:ras Proteins