SUMOylation of the GTPase Rac1 is required for optimal cell migration

TY - JOUR

T1 - SUMOylation of the GTPase Rac1 is required for optimal cell migration

AU - Castillo-Lluva, Sonia

AU - Tatham, Michael H.

AU - Jones, Richard C.

AU - Jaffray, Ellis G.

AU - Edmondson, Ricky D.

AU - Hay, Ronald T.

AU - Malliri, Angeliki

PY - 2010/11

Y1 - 2010/11

N2 - 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.

AB - 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.

KW - RHO-FAMILY GTPASES

KW - GROWTH-FACTOR

KW - IN-VIVO

KW - NUCLEAR-LOCALIZATION

KW - POLYBASIC REGION

KW - PIAS PROTEINS

KW - KINASE

KW - SUMO

KW - UBIQUITIN

KW - IDENTIFICATION

U2 - 10.1038/ncb2112

DO - 10.1038/ncb2112

M3 - Article

C2 - 20935639

SN - 1465-7392

VL - 12

SP - 1078-U70

JO - Nature Cell Biology

JF - Nature Cell Biology

IS - 11

ER -