title: RASSF4/AD037 is a potential ras effector/tumor suppressor of the RASSF family.
abstract: Activated Ras proteins interact with a broad range of effector proteins to induce a diverse series of biological consequences. Although typically associated with enhanced growth and transformation, activated Ras may also induce growth antagonistic effects such as senescence or apoptosis. It is now apparent that some of the growth-inhibitory properties of Ras are mediated via the RASSF family of Ras effector/tumor suppressors. To date, four members of this family have been identified (Nore1, RASSF1, RASSF2, and RASSF3). We now identify a fifth member of this group, RASSF4 (AD037). RASSF4 shows approximately 25% identity with RASSF1A and 60% identity with RASSF2. RASSF4 binds directly to activated K-Ras in a GTP-dependent manner via the effector domain, thus exhibiting the basic properties of a Ras effector. Overexpression of RASSF4 induces Ras-dependent apoptosis in 293-T cells and inhibits the growth of human tumor cell lines. Although broadly expressed in normal tissue, RASSF4 is frequently down-regulated by promoter methylation in human tumor cells. Thus, RASSF4 appears to be a new member of the RASSF family of potential Ras effector/tumor suppressors.
authors.affiliation: Department of Cell and Cancer Biology, National Cancer Institute, Rockville, Maryland 20850, USA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Eckfeld
authors.forename: Luke
authors.initials: L
authors.lastname: Hesson
authors.forename: Michele D
authors.initials: MD
authors.lastname: Vos
authors.forename: Ivan
authors.initials: I
authors.lastname: Bieche
authors.forename: Farida
authors.initials: F
authors.lastname: Latif
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Clark
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis / Q000502:physiology; D001483:Base Sequence; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015536:Down-Regulation; D020868:Gene Silencing; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: C495500:RASSF4 protein, human; D025521:Tumor Suppressor Proteins; D006160:Guanosine Triphosphate; D018631:ras Proteins