Correlation Engine 2.0
Clear Search sequence regions


  • cdc42 (7)
  • cdc42 protein (1)
  • cell movement (1)
  • GTP (4)
  • gtpase (1)
  • humans (1)
  • IQGAP1 (16)
  • protein human (2)
  • RAC1 (3)
  • rac1 protein (1)
  • ras GTPase (2)
  • regulates (1)
  • Rho GTPases (2)
  • ubiquitin (2)
  • Sizes of these terms reflect their relevance to your search.

    IQ motif-containing GTPase-activating protein 1 (IQGAP1) is a scaffold protein that interacts with numerous binding partners and thereby regulates fundamental biological processes. The functions of IQGAP1 are modulated by several mechanisms, including protein binding, self-association, subcellular localization, and phosphorylation. Proteome-wide screens have indicated that IQGAP1 is ubiquitinated, but the possible effects of this post-translational modification on its function are unknown. Here we characterized and evaluated the function of IQGAP1 ubiquitination. Using MS-based analysis in HEK293 cells, we identified six lysine residues (Lys-556, -1155, -1230, -1465, -1475, and -1528) as ubiquitination sites in IQGAP1. To elucidate the biological consequences of IQGAP1 ubiquitination, we converted each of these lysines to arginine and found that replacing two of these residues, Lys-1155 and Lys-1230, in the GAP-related domain of IQGAP1 (termed IQGAP1 GRD-2K) reduces its ubiquitination. Moreover, IQGAP1 GRD-2K bound a significantly greater proportion of the two Rho GTPases cell division cycle 42 (CDC42) and Rac family small GTPase 1 (RAC1) than did WT IQGAP1. Consistent with this observation, reconstitution of IQGAP1-null cells with IQGAP1 GRD-2K significantly increased the amount of active CDC42 and enhanced cell migration significantly more than WT IQGAP1. Our results reveal that ubiquitination of the CDC42 regulator IQGAP1 alters its ability to bind to and activate this GTPase, leading to physiological effects. Collectively, these findings expand our view of the role of ubiquitination in cell signaling and provide additional insight into CDC42 regulation.

    Citation

    Laëtitia Gorisse, Zhigang Li, Craig D Wagner, David K Worthylake, Francesca Zappacosta, Andrew C Hedman, Roland S Annan, David B Sacks. Ubiquitination of the scaffold protein IQGAP1 diminishes its interaction with and activation of the Rho GTPase CDC42. The Journal of biological chemistry. 2020 Apr 10;295(15):4822-4835

    Expand section icon Mesh Tags

    Expand section icon Substances


    PMID: 32094223

    View Full Text