Metastasis suppressor protein NDRG1 is destabilized by SUMO modification

초록

NDRG1 (N-myc Downstream Regulated Gene 1) is a metastasis protein which suppresses metastasis without affecting primary tumorigenesis. The regulatory mechanism of NDRG1 has not been revealed until recently. Here, we found that NDRG1 is a target of SUMO (small ubiquitin-like modifier) modification and NDRG1 is preferentially sumoylated by SUMO-2. Though NDRG1 has three putative SUMO consensus motifs, NDRG1 is not sumoylated at the conserved SUMO consensus motif. In this study, we found the major SUMO acceptor site of NDRG1. SUMO modification regulates the subcellular localization of NDRG1. SUMO-fused NDRG1 mutant shows the nuclear localization, while wild type and SUMO modification mutant NDRG1 reside predominantly in the cytosol. In addition, the SUMO modification of NDRG1 affects the protein stability of NDRG1. We found that wild type and SUMO modification mutant of NDRG1 protein was very stable but the protein stability of SUMO fused NDRG1 was dramatically decreased.