RhoH GTPase: A Key Regulator of Hematopoietic Cell Proliferation and Apoptosis?

Abstract

Rho GTPases are well characterized as critical regulators of cell growth and actin cytoskeleton in eukaryotic cells. The RhoE/Rnd3 subfamily member RhoH is hematopoietic-specific and GTPase deficient and thus is expected to be in the constitutively active, GTP-bound conformation. The activity of RhoH is likely regulated by the level of expression rather than GTP-binding/GTP-hydrolysis cycle in the cell. By RNAi based knockdown and overexpression approaches we recently have shown in hematopoietic progenitor cells that RhoH negatively impacts on growth factor-induced proliferation and survival and modulates chemokine-induced actin reorganization and cell migration. In addition, RhoH appears to counteract Rac GTPase activities, suggesting a possible mechanism by which RhoH functions as an antagonist of Rac signaling in the regulation of cell growth and actin-based functions in blood lineages.