AI Article Synopsis

  • Activated Ras proteins engage with various effector proteins, leading to different biological outcomes, including both cell growth and growth-inhibitory effects like senescence or apoptosis.
  • The RASSF family, known for its role as Ras effector/tumor suppressors, includes four known members, and research has now identified a fifth member, RASSF4, which shares significant genetic similarity with RASSF1A and RASSF2.
  • RASSF4 interacts directly with activated K-Ras and promotes apoptosis in certain cells while being frequently down-regulated in human tumors due to promoter methylation, highlighting its potential role as a tumor suppressor.

Article 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.

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http://dx.doi.org/10.1158/0008-5472.CAN-04-2065DOI Listing

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