SUMOylation of the GTPase Rac1 is required for optimal cell migration

Sonia Castillo-Lluva, Michael H. Tatham, Richard C. Jones, Ellis G. Jaffray, Ricky D. Edmondson, Ronald T. Hay, Angeliki Malliri

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    100 Citations (Scopus)

    Abstract

    The Rho-like GTPase, Rac1, induces cytoskeletal rearrangements required for cell migration. Rac activation is regulated through a number of mechanisms, including control of nucleotide exchange and hydrolysis, regulation of subcellular localization or modulation of protein-expression levels(1-3). Here, we demonstrate that (the small ubiquitin-like modifier) SUMO E3-ligase, PIAS3, interacts with Rac1 and is required for increased Rac activation and optimal cell migration in response to hepatocyte growth factor (HGF) signalling. Rac1 can be conjugated to SUMO-1 in response to hepatocyte growth factor treatment and SUMOylation is enhanced by PIAS3. Furthermore, we identify non-consensus sites within the polybasic region of Rac1 as the main location for SUMO conjugation. PIAS3-mediated SUMOylation of Rac1 controls the levels of Rac1-GTP and the ability of Rac1 to stimulate lamellipodia, cell migration and invasion. The finding that a Ras superfamily member can be SUMOylated provides insights into the regulation of these critical mediators of cell behaviour. Our data reveal a role for SUMO in the regulation of cell migration and invasion.

    Original languageEnglish
    Pages (from-to)1078-U70
    Number of pages21
    JournalNature Cell Biology
    Volume12
    Issue number11
    DOIs
    Publication statusPublished - Nov 2010

    Keywords

    • RHO-FAMILY GTPASES
    • GROWTH-FACTOR
    • IN-VIVO
    • NUCLEAR-LOCALIZATION
    • POLYBASIC REGION
    • PIAS PROTEINS
    • KINASE
    • SUMO
    • UBIQUITIN
    • IDENTIFICATION

    Cite this

    Castillo-Lluva, S., Tatham, M. H., Jones, R. C., Jaffray, E. G., Edmondson, R. D., Hay, R. T., & Malliri, A. (2010). SUMOylation of the GTPase Rac1 is required for optimal cell migration. Nature Cell Biology, 12(11), 1078-U70. https://doi.org/10.1038/ncb2112