Vos Michele D, Ellis Chad A, Elam Candice, Ulku Aylin S, Taylor Barbara J, Clark Geoffrey J
Department of Cell and Cancer Biology, NCI, National Institutes of Health, Rockville, Maryland 20850-3300, USA.
J Biol Chem. 2003 Jul 25;278(30):28045-51. doi: 10.1074/jbc.M300554200. Epub 2003 May 5.
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.
Ras蛋白通过与多种效应蛋白相互作用来调节广泛的生物学过程。虽然激活形式的Ras经常与肿瘤发生相关，但它们也可能引发生长拮抗作用。这些作用包括衰老、细胞周期停滞、分化和凋亡。对这些生长抑制活性背后的机制了解相对较少。最近，两个相关的新型Ras效应蛋白NORE1和RASSF1已被确定为凋亡和细胞周期停滞的介质。这两种蛋白都表现出许多通常与肿瘤抑制因子相关的特性。我们现在鉴定出该家族的一个新成员，命名为RASSF2。RASSF2通过Ras效应结构域以GTP依赖的方式直接与K-Ras结合。然而，RASSF2与H-Ras的相互作用较弱。此外，RASSF2促进凋亡和细胞周期停滞，并且在肺癌细胞系中经常下调。因此，我们将RASSF2鉴定为RASSF1家族Ras效应蛋白/肿瘤抑制因子的一个新成员，它表现出与K-Ras相互作用的特异性。
