The Rnd proteins, which form a distinct sub-group of the Rho family of small GTP-binding proteins, have been shown to regulate the organization of the actin cytoskeleton in several tissues []. This entry represents RhoE (also known as Rnd3 or Rho8), which is a member of the Rnd subfamily. Unlike other small G proteins, RhoE, along with two other proteins Rnd1/Rho6 and Rnd2/RhoN, does not hydrolyze GTP []. This is due to changes in key amino acids involved in catalysing GTP hydrolysis []. RhoE is known to bind the serine-threonine kinase ROCK I. Unphosphorylated RhoE associates primarily with membranes, but ROCK I-phosphorylated RhoE localizes in the cytosol []. Phosphorylation of RhoE correlates with its activity in disrupting RhoA-induced stress fibres and inhibiting Ras-induced fibroblast transformation []. In mammary epithelial tumor cells, RhoE regulates the assembly of the apical junction complex and tight junction formation []. In cells that lack stress fibres, such as macrophages and monocytes, RhoE induces a redistribution of actin, causing morphological changes in the cell []. In addition, RhoE has been shown to inhibit cell cycle progression in G1 phase at a point upstream of the pRb family pocket protein checkpoint []. RhoE has also been shown to inhibit Ras- and Raf-induced fibroblast transformation. RhoE is underexpressed in prostate cancer cells both in vitro and in vivo; re-expression of RhoE suppresses cell cycle progression and increases apoptosis, suggesting it may play a role in tumor suppression [].
