Title: RhoGDI SUMOylation at Lys-138 increases its binding activity to Rho GTPase and its inhibiting cancer cell motility.
Authors: Yu, Jianxiu; Zhang, Dongyun; Liu, Jinyi; Li, Jingxia; Yu, Yonghui; Wu, Xue-Ru; Huang, Chuanshu
Published In J Biol Chem, (2012 Apr 20)
Abstract: The Rho GDP dissociation inhibitor (RhoGDI) can bind to small GTPases and keep them in a biologically inactive state in cytoplasm, through which it affects actin polymerization and cell motility. However, mechanisms underlying how RhoGDI regulates Rho GTPase complex formation/membrane extraction/GTPase dissociation remain largely unexplored. Our previous studies reported that X-linked inhibitor of apoptosis protein (XIAP) interacted with RhoGDI via its RING domain and negatively modulated RhoGDI SUMOylation and HCT116 cancer cell migration. Here, we identified that RhoGDI SUMOylation specifically occurred at Lys-138, which was inhibited by XIAP domain. We further demonstrated that RhoGDI SUMOylation at Lys-138 was crucial for inhibiting actin polymerization and cytoskeleton formation as well as cancer cell motility. Moreover, SUMO-RhoGDI had a much higher binding affinity to small Rho GTPase compared with the un-SUMOylated form of RhoGDI. Taken together, our study demonstrated a novel modification of RhoGDI, SUMOylation at Lys-138, which played a key role in regulating Rho GTPase activation in cancer cells. The physiological regulation of RhoGDI SUMOylation by the RING domain of XIAP may account for modulation of cancer cell invasion and metastasis by XIAP.
PubMed ID: 22393046
MeSH Terms: Cell Line, Tumor; Cell Movement; Gene Expression Regulation, Neoplastic*; Guanine Nucleotide Dissociation Inhibitors/metabolism*; Humans; Lysine/chemistry*; Models, Biological; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms/drug therapy*; Neoplasms/metabolism; Neoplasms/pathology*; Sumoylation; Wound Healing; X-Linked Inhibitor of Apoptosis Protein/metabolism; rho GTP-Binding Proteins/chemistry*; rho GTP-Binding Proteins/metabolism; rho Guanine Nucleotide Dissociation Inhibitor alpha; rho-Specific Guanine Nucleotide Dissociation Inhibitors