Ra1A interacts with ZONAB in a cell density-dependent manner and regulates its transcriptional activity

Ral proteins are members of the Ras superfamily of small GTPases and are involved in signalling pathways for actin cytoskeleton remodelling, cell cycle control, cellular transformation and vesicle transport. To identify novel RalA effector proteins, we used the reverse Ras recruitment system and found that RalA interacts with a Y-box transcription factor, ZO-1-associated nucleic acid-binding protein (ZONAB), in a GTP-dependent manner. The amount of the RalA-ZONAB complex increases as epithelial cells become more dense and increase cell contacts. The RalA-ZONAB interaction results in a relief of transcriptional repression of a ZONAB-regulated promoter. Additionally, expression of oncogenic Ras alleviates transcriptional repression by ZONAB in a RalA-dependent manner. The data presented here implicate the RalA/ZONAB interaction in the regulation of ZONAB function.