Mutations that promote unrestricted growth are usually not themselves sufficient to cause tumorigenesis, because such uncontrolled growth triggers mechanisms that lead to apoptosis. Activation of the small guanosine triphosphatase (GTPase) Ras, for example, promotes apoptosis along with its effects on proliferation and transformation. Vos et al. identify a candidate effector of Ras that could mediate signals causing cell death. The authors discovered RASSF1 by searching a database for human genes encoding Ras-association domains. Meanwhile the same protein was identified as a tumor suppressor. In transfected cells, RASSF1C (a splice variant) interacted specifically with GTP-bound, active Ras. Transient transfection of RASSF1C into human 293-T cells inhibited cell proliferation, apparently by promoting apoptosis. This effect of RASSF1C was accentuated when activated Ras was also expressed in the cells. The authors conclude that RASSF1 may be a Ras effector that mediates apoptotic signals. If so, inactivation of RASSF1 would be expected to contribute to tumorigenesis when combined with activating mutations in Ras.
Vos, M.D., Ellis, C.A., Bell, A., Birrer, M.J., and Clark, G.J. (2000) Ras uses the novel tumor suppressor RASSF1 as an effector to mediate apoptosis. J. Biol. Chem. 275: 35669-35672. [Abstract] [Full Text]