Functions of deleted in liver cancer (DLC1) in cell dynamics

Abstract

Combining proteomics, biochemical, structural and cellular studies, our current work had identified the eukaryote elongation factor 1A1 (EF1A1) as a novel interacting partner for the SAM domain of DLC1, defined their interaction mechanism through identifying important motif/domain involved for their interaction and investigated the functional significance of their interaction in cell migration. Significantly, we have shown that hydrophobic residues F38 and L39 in DLC1-SAM form an indispensable interacting motif for the interaction with EF1A1. Using DLC1 mutants mutated at these residues, we demonstrated that SAM domain is necessary for DLC1 to translocate EF1A1 to the membrane periphery and ruffles upon fibroblast growth factor stimulation, and it acts as an auxiliary switch to the anti-metastastic RhoGAP domain.These findings shed light on the mechanism of SAM domain of DLC1 cooperate with the RhoGAP activity to modulate DLC1b s function in cell dynamic control.