Jose A Cancelas1, David A Williams. 1. Division of Experimental Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Abstract
PURPOSE OF REVIEW: Rho GTPases are key molecular switches controlling the transduction of external signals to cytoplasmic and nuclear effectors. In the last few years, the development of genetic and pharmacological tools has allowed a more precise definition of the specific roles of Rho GTPases in hematopoietic stem cells (HSCs) and progeny of these cells. Rho GTPases are now known to be crucial in HSCs response to hematopoietic microenvironment cues. This article will review the known HSC functions, which are regulated by Rho GTPases. RECENT FINDINGS: This review analyzes the latest data on how different Rho GTPases control adhesion, migration, retention, proliferation, survival, senescence and oncogenic transformation of HSCs and relates these new findings to the physiological functions of these cells. SUMMARY: The development of small molecule inhibitors with ability to interfere Rho GTPase activation by guanine nucleotide exchange factors offers new therapeutic strategies to manipulate the function of HSCs.
PURPOSE OF REVIEW: Rho GTPases are key molecular switches controlling the transduction of external signals to cytoplasmic and nuclear effectors. In the last few years, the development of genetic and pharmacological tools has allowed a more precise definition of the specific roles of Rho GTPases in hematopoietic stem cells (HSCs) and progeny of these cells. Rho GTPases are now known to be crucial in HSCs response to hematopoietic microenvironment cues. This article will review the known HSC functions, which are regulated by Rho GTPases. RECENT FINDINGS: This review analyzes the latest data on how different Rho GTPases control adhesion, migration, retention, proliferation, survival, senescence and oncogenic transformation of HSCs and relates these new findings to the physiological functions of these cells. SUMMARY: The development of small molecule inhibitors with ability to interfere Rho GTPase activation by guanine nucleotide exchange factors offers new therapeutic strategies to manipulate the function of HSCs.
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