A role for Ral GTPase-activating protein subunit β in mitotic regulation.

Ral proteins are small GTPases that play critical roles in normal physiology and in oncogenesis. There is little information on the GTPase-activating proteins (GAPs) that downregulate their activity. Here, we provide evidence that the noncatalytic β subunit of RalGAPα1/2 β complexes is involved in mitotic control. RalGAPβ localizes to the Golgi and nucleus during interphase, and relocalizes to the mitotic spindle and cytokinetic intercellular bridge during mitosis. Depletion of RalGAPβ causes chromosome misalignment and decreases the amount of mitotic cyclin B1, disturbing the metaphase-to-anaphase transition. Overexpression of RalGAPβ interferes with cell division, leading to binucleation and multinucleation, and cell death. We propose that RalGAPβ plays an essential role in the sequential progression of mitosis by controlling the spatial and temporal activation of Ral GTPases in the spindle assembly checkpoint (SAC) and cytokinesis. Deregulation of RalGAPβ might cause genomic instability, leading to human carcinogenesis.