title: Rho regulation: DLC proteins in space and time.
abstract: Rho GTPases function as molecular switches that connect changes of the external environment to intracellular signaling pathways. They are active at various subcellular sites and require fast and tight regulation to fulfill their role as transducers of extracellular stimuli. New imaging technologies visualizing the active states of Rho proteins in living cells elucidated the necessity of precise spatiotemporal activation of the GTPases. The local regulation of Rho proteins is coordinated by the interaction with different guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) that turn on and off GTPase signaling to downstream effectors. GEFs and GAPs thus serve as critical signaling nodes that specify the amplitude and duration of a particular Rho signaling pathway. Despite their importance in Rho regulation, the molecular aspects underlying the spatiotemporal control of the regulators themselves are still largely elusive. In this review we will focus on the Deleted in Liver Cancer (DLC) family of RhoGAP proteins and summarize the evidence gathered over the past years revealing their different subcellular localizations that might account for isoform-specific functions. We will also highlight the importance of their tightly controlled expression in the context of neoplastic transformation.
authors.affiliation: University of Stuttgart, Institute of Cell Biology and Immunology, Allmandring 31, 70569 Stuttgart, Germany.
authors.forename: Anja C
authors.initials: AC
authors.lastname: Braun
authors.affiliation: University of Stuttgart, Institute of Cell Biology and Immunology, Allmandring 31, 70569 Stuttgart, Germany. Electronic address: monilola.olayioye@izi.uni-stuttgart.de.
authors.forename: Monilola A
authors.initials: MA
authors.lastname: Olayioye
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D002467:Cell Nucleus / Q000201:enzymology; D022081:Cell Surface Extensions / Q000201:enzymology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D022083:Cytoplasmic Structures / Q000201:enzymology; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D064067:Rho Guanine Nucleotide Exchange Factors / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: C112352:DLC1 protein, human; D020690:GTPase-Activating Proteins; D064067:Rho Guanine Nucleotide Exchange Factors; C473607:STARD13 protein, human; D025521:Tumor Suppressor Proteins; D020741:rho GTP-Binding Proteins
keywords: Deleted in liver cancer 1–3 (DLC1/StarD12, DLC2/StarD13, DLC3/StarD8); GTPase activating protein (GAP); Rho signaling; Subcellular localization; Tumor suppression