Intheir study,they show that RalA, a key mediator of Ras
transformation, is
also linked to the
translational machinery.
At least part of this
linkage, however, is independent of mTOR and acts through RalBP1 to
suppress cdc42-mediated activation of S6 kinase and the translation of
the antiapoptotic protein FLIPS.
This action, rather than contributing
to
transformation, opens a latent tumor-suppressive mechanism that can
be activated by tumor necrosis factor-related apoptosis-inducing
ligand.
The results show that the
translational machinery is linked
to tumor suppression as well as cell-proliferative pathways and that
the reestablishment of cell death pathways by activation of the Ral
oncogenic program provides a means for selective therapeutic targeting
of Ral-driven malignancies.