Regulation of RhoA activation and cytoskeletal organization by acetylation.

Rho GTPases regulate cell motility in a large part through control of actin cytoskeletal organization. The activation state of Rho proteins is regulated by a wide variety of guanine nucleotide exchange factors (GEFs) and GTPase activating proteins that are differentially expressed among cell types and disease states. The RhoA specific GEF neuroepithelial transforming gene 1 (Net1) is highly expressed in many cancer cells and stimulates cell motility, invasion and cell spreading in response to a variety of ligands. A key feature of Net1 proteins is that they are sequestered in the nucleus in the absence of a motility stimulus. We have recently found that accumulation of the Net1A isoform outside the nucleus, which is the primary Net1 isoform controlling cell motility, is regulated by its acetylation status. Here, we describe acetylation as a novel mechanism of RhoGEF regulation in cell motility that can be targeted in cancer and metastasis.