SUMOylation of the GTPase Rac1 is required for optimal cell migration
Open Access
- 10 October 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 12 (11), 1078-1085
- https://doi.org/10.1038/ncb2112
Abstract
The SUMO E3 ligase PIAS3 is shown to promote Rac1 SUMOylation. This modification stimulates Rac1 activity and regulates its ability to drive lamellipodium formation. 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 levels1,2,3. Here, we identify 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. We demonstrate that Rac1 can be conjugated to SUMO-1 in response to hepatocyte growth factor treatment and that SUMOylation is enhanced by PIAS3. Furthermore, we identify non-consensus sites within the polybasic region of Rac1 as the main location for SUMO conjugation. We demonstrate that 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 an insight 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.Keywords
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