Genomes and Genes
Gene Symbol: Rheb
Description: Ras homolog enriched in brain
Alias: CG1081, DReb, Dm Rheb, DmRheb, Dmel\CG1081, Q9VND8, RHEB, RheB, dRheb, rheb, Ras homolog enriched in brain, CG1081-PA, CG1081-PB, RAS homolog enriched in brain, Ras homolog enriched in brain ortholog, Ras homologue enriched in brain, Ras homology enriched in brain, Rheb-PA, Rheb-PB
Species: fruit fly
- Kim E, Goraksha Hicks P, Li L, Neufeld T, Guan K. Regulation of TORC1 by Rag GTPases in nutrient response. Nat Cell Biol. 2008;10:935-45 pubmed publisher..Genetic studies in Drosophila also show that Rag GTPases regulate cell growth, autophagy and animal viability during starvation. Our studies establish a function of Rag GTPases in TORC1 activation in response to amino acid signals. ..
- Juhasz G, Hill J, Yan Y, Sass M, Baehrecke E, Backer J, et al. The class III PI(3)K Vps34 promotes autophagy and endocytosis but not TOR signaling in Drosophila. J Cell Biol. 2008;181:655-66 pubmed publisher..Our results suggest that Vps34 is regulated by TOR-dependent nutrient signals directly at sites of autophagosome formation. ..
- Kockel L, Kerr K, Melnick M, Brückner K, Hebrok M, Perrimon N. Dynamic switch of negative feedback regulation in Drosophila Akt-TOR signaling. PLoS Genet. 2010;6:e1000990 pubmed publisher..These results illustrate how the Akt-TOR pathway dynamically adapts the routing of negative feedback in response to the activity load of its signaling circuit in vivo. ..
- Martín Peña A, Acebes A, Rodriguez J, Sorribes A, de Polavieja G, Fernandez Funez P, et al. Age-independent synaptogenesis by phosphoinositide 3 kinase. J Neurosci. 2006;26:10199-208 pubmed..Thus, we propose that PI3K stimulation can be applied to prevent or delay synapse loss in normal aging and in neurological disorders. ..
- Saucedo L, Gao X, Chiarelli D, Li L, Pan D, Edgar B. Rheb promotes cell growth as a component of the insulin/TOR signalling network. Nat Cell Biol. 2003;5:566-71 pubmed..In a screen for novel regulators of growth, we identified Rheb (Ras homologue enriched in brain), a member of the Ras superfamily of GTP-binding proteins...
- Grewal S, Evans J, Edgar B. Drosophila TIF-IA is required for ribosome synthesis and cell growth and is regulated by the TOR pathway. J Cell Biol. 2007;179:1105-13 pubmed..Stimulation of rRNA synthesis by TIF-IA may therefore provide a feed-forward mechanism to coregulate the levels of other ribosome components. ..
- Chang Y, Neufeld T. An Atg1/Atg13 complex with multiple roles in TOR-mediated autophagy regulation. Mol Biol Cell. 2009;20:2004-14 pubmed publisher..Atg1-Atg13 complexes thus function at multiple levels to mediate and adjust nutrient-dependent autophagic signaling. ..
- Lee S, Kim S, Lee J, Park J, Lee G, Kim Y, et al. ATG1, an autophagy regulator, inhibits cell growth by negatively regulating S6 kinase. EMBO Rep. 2007;8:360-5 pubmed..Taken together, our genetic and biochemical results strongly indicate crosstalk between autophagy and cell growth regulation. ..
- Karbowniczek M, Zitserman D, Khabibullin D, Hartman T, Yu J, Morrison T, et al. The evolutionarily conserved TSC/Rheb pathway activates Notch in tuberous sclerosis complex and Drosophila external sensory organ development. J Clin Invest. 2010;120:93-102 pubmed publisher..We report here that inactivation of Tsc1 and overexpression of the Ras homolog Rheb each resulted in duplication of the bristle and socket cells, progeny of the pIIa cell, and loss of the neuronal ..
- Zhang Y, Gao X, Saucedo L, Ru B, Edgar B, Pan D. Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins. Nat Cell Biol. 2003;5:578-81 pubmed..Here we show that the small GTPase Rheb (Ras homologue enriched in brain) is a direct target of Tsc2 GAP activity both in vivo and in vitro...
- Hsieh T, Nicolay B, Frolov M, Moon N. Tuberous sclerosis complex 1 regulates dE2F1 expression during development and cooperates with RBF1 to control proliferation and survival. PLoS Genet. 2010;6:e1001071 pubmed publisher..revealed that the protein level of dE2F1 is increased in tsc1 or tsc2 mutant cells and conversely decreased in rheb or dTor mutant cells...
- Hall D, Grewal S, de la Cruz A, Edgar B. Rheb-TOR signaling promotes protein synthesis, but not glucose or amino acid import, in Drosophila. BMC Biol. 2007;5:10 pubmedThe Ras-related GTPase, Rheb, regulates the growth of animal cells...
- Patel P, Tamanoi F. Increased Rheb-TOR signaling enhances sensitivity of the whole organism to oxidative stress. J Cell Sci. 2006;119:4285-92 pubmed..The well-conserved Rheb-Target-of-rapamycin (TOR)-S6-kinase (S6K) signaling pathway regulates several cellular processes and has been shown ..
- Stocker H, Radimerski T, Schindelholz B, Wittwer F, Belawat P, Daram P, et al. Rheb is an essential regulator of S6K in controlling cell growth in Drosophila. Nat Cell Biol. 2003;5:559-65 pubmed..Here we describe a new effector in growth control, the small GTPase Rheb (Ras homologue enriched in brain)...
- Findlay G, Yan L, Procter J, Mieulet V, Lamb R. A MAP4 kinase related to Ste20 is a nutrient-sensitive regulator of mTOR signalling. Biochem J. 2007;403:13-20 pubmed..Our results therefore suggest a model whereby nutrients signal to mTORC1 via activation of MAP4K3. ..
- Dekanty A, Lavista Llanos S, Irisarri M, Oldham S, Wappner P. The insulin-PI3K/TOR pathway induces a HIF-dependent transcriptional response in Drosophila by promoting nuclear localization of HIF-alpha/Sima. J Cell Sci. 2005;118:5431-41 pubmed..We conclude that regulation of HIF-alpha/Sima by the PI3K-AKT-TOR pathway is a major conserved mode of regulation of the HIF-dependent transcriptional response in Drosophila. ..
- Bateman J, McNeill H. Temporal control of differentiation by the insulin receptor/tor pathway in Drosophila. Cell. 2004;119:87-96 pubmed..Examination of InR, PI3K, PTEN, Tor, Rheb, and S6 kinase mutants demonstrates that increased InR signaling leads to precocious differentiation while ..
- Sousa Nunes R, Yee L, Gould A. Fat cells reactivate quiescent neuroblasts via TOR and glial insulin relays in Drosophila. Nature. 2011;471:508-12 pubmed publisher..This mechanism indicates that dietary nutrients and remote organs, as well as local niches, are key regulators of transitions in stem-cell behaviour...
- Rehmann H, Bruning M, Berghaus C, Schwarten M, Kohler K, Stocker H, et al. Biochemical characterisation of TCTP questions its function as a guanine nucleotide exchange factor for Rheb. FEBS Lett. 2008;582:3005-10 pubmed publisher..It has been postulated to serve as a guanine nucleotide exchange factor for the small G-protein Rheb. Rheb functions in the PI3 kinase/mTOR pathway...
- Goberdhan D, Meredith D, Boyd C, Wilson C. PAT-related amino acid transporters regulate growth via a novel mechanism that does not require bulk transport of amino acids. Development. 2005;132:2365-75 pubmed..As PATH is likely to be saturated in vivo, we propose that one specialised function of high-affinity PAT-related molecules is to maintain growth as local nutrient levels fluctuate during development. ..
- Zielke N, Kim K, Tran V, Shibutani S, Bravo M, Nagarajan S, et al. Control of Drosophila endocycles by E2F and CRL4(CDT2). Nature. 2011;480:123-7 pubmed publisher..Many of the regulatory interactions essential to this novel cell cycle oscillator are conserved in animals and plants, indicating that elements of this mechanism act in most growth-dependent cell cycles. ..
- Brown H, Kaun K, Edgar B. The small GTPase Rheb affects central brain neuronal morphology and memory formation in Drosophila. PLoS ONE. 2012;7:e44888 pubmed publisher..We overexpressed Rheb, an upstream regulator of TOR, in two different subsets of D...
- Barth J, Szabad J, Hafen E, Kohler K. Autophagy in Drosophila ovaries is induced by starvation and is required for oogenesis. Cell Death Differ. 2011;18:915-24 pubmed publisher..Our data establish an important function for autophagy during oogenesis and contributes to the understanding of the role of autophagy in animal development...
- McNeill H, Craig G, Bateman J. Regulation of neurogenesis and epidermal growth factor receptor signaling by the insulin receptor/target of rapamycin pathway in Drosophila. Genetics. 2008;179:843-53 pubmed publisher..Together these data suggest that InR/TOR signaling regulates the timing of differentiation through modulation of EGFR target genes in developing photoreceptors. ..
- Li B, Gordon G, Du C, Xu J, Du W. Specific killing of Rb mutant cancer cells by inactivating TSC2. Cancer Cell. 2010;17:469-80 pubmed publisher..Inactivation of TSC2 and Rb synergistically induce oxidative stress via increased protein synthesis, inhibited de novo lipid synthesis, and decreased reactive oxygen species scavenger enzyme SOD2 induction. ..
- Scott R, Schuldiner O, Neufeld T. Role and regulation of starvation-induced autophagy in the Drosophila fat body. Dev Cell. 2004;7:167-78 pubmed..Here, we show that signaling through TOR and its upstream regulators PI3K and Rheb is necessary and sufficient to suppress starvation-induced autophagy in the Drosophila fat body...
- Hsu Y, Chern J, Cai Y, Liu M, Choi K. Drosophila TCTP is essential for growth and proliferation through regulation of dRheb GTPase. Nature. 2007;445:785-8 pubmed..Activation of the TSC pathway is mediated by Rheb (Ras homologue enriched in brain), a Ras superfamily GTPase...
- Hennig K, Colombani J, Neufeld T. TOR coordinates bulk and targeted endocytosis in the Drosophila melanogaster fat body to regulate cell growth. J Cell Biol. 2006;173:963-74 pubmed..Our data indicate that endocytosis acts both as an effector function downstream of TOR and as a physiologically relevant regulator of TOR signaling...
- Harvey K, Mattila J, Sofer A, Bennett F, Ramsey M, Ellisen L, et al. FOXO-regulated transcription restricts overgrowth of Tsc mutant organs. J Cell Biol. 2008;180:691-6 pubmed publisher..Analogous transcriptional changes are observed in mammalian cells, which implies that FOXO attenuates TOR-driven growth in diverse species. ..
- Reis T, Edgar B. Negative regulation of dE2F1 by cyclin-dependent kinases controls cell cycle timing. Cell. 2004;117:253-64 pubmed..g., by ectopic Dacapo, dWee1, dMyc, or Rheb)...
- Scott R, Juhasz G, Neufeld T. Direct induction of autophagy by Atg1 inhibits cell growth and induces apoptotic cell death. Curr Biol. 2007;17:1-11 pubmed..Furthermore, this work identifies autophagy as a critical mechanism by which inhibition of TOR signaling leads to reduced cell growth. ..
- Wang T, Lao U, Edgar B. TOR-mediated autophagy regulates cell death in Drosophila neurodegenerative disease. J Cell Biol. 2009;186:703-11 pubmed publisher..Thus, our data indicate that TOR induces cell death by suppressing autophagy and provide direct genetic evidence that autophagy alleviates cell death in several common types of neurodegenerative disease. ..
- Kuhn H, Sopko R, Coughlin M, Perrimon N, Mitchison T. The Atg1-Tor pathway regulates yolk catabolism in Drosophila embryos. Development. 2015;142:3869-78 pubmed publisher..We propose that the conserved Tor metabolic sensing pathway regulates yolk catabolism, similar to Tor-dependent metabolic regulation on the lysosome. ..
- Kapuria S, Karpac J, Biteau B, Hwangbo D, Jasper H. Notch-mediated suppression of TSC2 expression regulates cell differentiation in the Drosophila intestinal stem cell lineage. PLoS Genet. 2012;8:e1003045 pubmed publisher..Regulation of TSC/TOR activity by N signaling thus emerges as critical for maintenance and differentiation in somatic stem cell lineages. ..
- Haberman A, Akbar M, Ray S, KRAMER H. Drosophila acinus encodes a novel regulator of endocytic and autophagic trafficking. Development. 2010;137:2157-66 pubmed publisher..Taken together, our data show that dacn encodes a regulator of endosomal and autophagosomal dynamics, modulating developmental signaling and the cellular response to starvation. ..
- Nie Y, Li Q, Amcheslavsky A, Duhart J, Veraksa A, Stocker H, et al. Bunched and Madm Function Downstream of Tuberous Sclerosis Complex to Regulate the Growth of Intestinal Stem Cells in Drosophila. Stem Cell Rev. 2015;11:813-25 pubmed publisher..cell growth and 4EBP phosphorylation phenotypes induced by loss of Tuberous Sclerosis Complex or overexpression of Rheb were suppressed by the loss of Bunched or Madm...
- Luo J, Liu Y, Nassel D. Insulin/IGF-regulated size scaling of neuroendocrine cells expressing the bHLH transcription factor Dimmed in Drosophila. PLoS Genet. 2013;9:e1004052 pubmed publisher..be induced by targeted overexpression of nutrient-dependent TOR (target of rapamycin) signaling components, such as Rheb (small GTPase), TOR and S6K (S6 kinase)...
- Rawls J. Analysis of pyrimidine catabolism in Drosophila melanogaster using epistatic interactions with mutations of pyrimidine biosynthesis and beta-alanine metabolism. Genetics. 2006;172:1665-74 pubmed..These results are discussed in the context of similar consequences of 5-fluoropyrimidine toxicity and pyrimidine catabolism mutations in humans. ..
- Axelrod S, Saez L, Young M. Studying circadian rhythm and sleep using genetic screens in Drosophila. Methods Enzymol. 2015;551:3-27 pubmed publisher..We discuss the different screening approaches in light of the literature and published and unpublished sleep and rhythm screens utilizing ethyl methanesulfonate mutagenesis and transgenic RNAi from our lab. ..
- Ferreira A, MilÃ¡n M. Dally Proteoglycan Mediates the Autonomous and Nonautonomous Effects on Tissue Growth Caused by Activation of the PI3K and TOR Pathways. PLoS Biol. 2015;13:e1002239 pubmed publisher..We present evidence that Dally also contributes to integrating nutrient sensing and organ scaling, the fitting of pattern to size. ..
- Bates K, Sung C, Hilson L, Robinow S. unfulfilled interacting genes display branch-specific roles in the development of mushroom body axons in Drosophila melanogaster. G3 (Bethesda). 2014;4:693-706 pubmed publisher..misguided dorsally in five double heterozygote combinations (;unf/+;axin/+, unf/+;Fps85D/+, ;unf/+;Tsc1/+, ;unf/+;Rheb/+, ;unf/+;msn/+)...
- Kim W, Jang Y, Yang J, Chung J. Spatial Activation of TORC1 Is Regulated by Hedgehog and E2F1 Signaling in the Drosophila Eye. Dev Cell. 2017;42:363-375.e4 pubmed publisher..Based on this evolutionarily conserved regulation of TORC1 by Hh signaling, we propose that Hh-dependent developmental signaling pathways spatially regulate TORC1 activity in multicellular organisms. ..
- Doumanis J, Wada K, Kino Y, Moore A, Nukina N. RNAi screening in Drosophila cells identifies new modifiers of mutant huntingtin aggregation. PLoS ONE. 2009;4:e7275 pubmed publisher..Newly identified modifiers including genes related to nuclear transport, nucleotide processes, and signaling, may be involved in polyglutamine aggregate formation and Huntington disease cascades. ..
- Eddison M, Guarnieri D, Cheng L, Liu C, Moffat K, Davis G, et al. arouser reveals a role for synapse number in the regulation of ethanol sensitivity. Neuron. 2011;70:979-90 pubmed publisher..We thus show that a developmental abnormality affecting synapse number and ethanol sensitivity is not permanent and can be reversed by manipulating the environment of the adult fly. ..
- Khurana V, Lu Y, Steinhilb M, Oldham S, Shulman J, Feany M. TOR-mediated cell-cycle activation causes neurodegeneration in a Drosophila tauopathy model. Curr Biol. 2006;16:230-41 pubmed..TOR-mediated cell-cycle activation causes neurodegeneration in a Drosophila tauopathy model, identifying TOR and the cell cycle as potential therapeutic targets in tauopathies and AD. ..
- Smith Bolton R, Worley M, Kanda H, Hariharan I. Regenerative growth in Drosophila imaginal discs is regulated by Wingless and Myc. Dev Cell. 2009;16:797-809 pubmed publisher..This system is conducive to forward genetic screens, enabling an unbiased search for genes that regulate both the extent of and the capacity for regeneration. ..
- Rojas Benítez D, Thiaville P, de CrÃ©cy Lagard V, Glavic A. The Levels of a Universally Conserved tRNA Modification Regulate Cell Growth. J Biol Chem. 2015;290:18699-707 pubmed publisher..These findings reveal an unprecedented relationship between the translation machinery and TOR, where translation efficiency, limited by the availability of t(6)A-modified tRNA, determines growth potential in eukaryotic cells. ..
- O Farrell F, Wang S, Katheder N, Rusten T, Samakovlis C. Two-tiered control of epithelial growth and autophagy by the insulin receptor and the ret-like receptor, stitcher. PLoS Biol. 2013;11:e1001612 pubmed publisher..The combined activities of Stit and InR in ectodermal epithelial tissues provide an RTK-mediated, two-tiered reaction threshold to varying nutritional conditions that promote epithelial organ growth even at low levels of InR signaling. ..
- Dimitroff B, Howe K, Watson A, Campion B, Lee H, Zhao N, et al. Diet and energy-sensing inputs affect TorC1-mediated axon misrouting but not TorC2-directed synapse growth in a Drosophila model of tuberous sclerosis. PLoS ONE. 2012;7:e30722 pubmed publisher..In Drosophila, neuron-specific overexpression of Rheb, the direct downstream target inhibited by Tsc1/Tsc2, produced significant synapse overgrowth, axon misrouting, and ..
- Patch K, Stewart S, Welch A, Ward R. A second-site noncomplementation screen for modifiers of Rho1 signaling during imaginal disc morphogenesis in Drosophila. PLoS ONE. 2009;4:e7574 pubmed publisher..In addition, we identified Cdc42, Rheb and Sc2 as novel Rho1-interacting genes involved in adult leg development...
- Alvarez Ponce D, Guirao Rico S, Orengo D, Segarra C, Rozas J, Aguade M. Molecular population genetics of the insulin/TOR signal transduction pathway: a network-level analysis in Drosophila melanogaster. Mol Biol Evol. 2012;29:123-32 pubmed publisher..The detected polarity would be, therefore, intrinsic to the IT pathway architecture and function. ..
- Vachias C, Fritsch C, Pouchin P, Bardot O, Mirouse V. Tight coordination of growth and differentiation between germline and soma provides robustness for drosophila egg development. Cell Rep. 2014;9:531-41 pubmed publisher..Altogether, our results reveal an integrated and particularly robust mechanism ensuring the spatial and temporal coordination of tissue size, cell size, and cell differentiation for the proper development of two adjacent tissues. ..
- Kuleesha Y, Puah W, Wasser M. A model of muscle atrophy based on live microscopy of muscle remodelling in Drosophila metamorphosis. R Soc Open Sci. 2016;3:150517 pubmed publisher..In conclusion, studying muscle remodelling in metamorphosis can provide new insights into the cell biology of muscle wasting. ..
- Gupta A, Toscano S, Trivedi D, Jones D, Mathre S, Clarke J, et al. Phosphatidylinositol 5-phosphate 4-kinase (PIP4K) regulates TOR signaling and cell growth during Drosophila development. Proc Natl Acad Sci U S A. 2013;110:5963-8 pubmed publisher..Together, these results define dPIP4K activity as a regulator of cell growth and TOR signaling during larval development. ..
- Killip L, Grewal S. DREF is required for cell and organismal growth in Drosophila and functions downstream of the nutrition/TOR pathway. Dev Biol. 2012;371:191-202 pubmed publisher..Given that DREF is conserved, this role may also be important in the control of growth in other animals. ..
- Murillo Maldonado J, Sánchez Chávez G, Salgado L, Salceda R, Riesgo Escovar J. Drosophila insulin pathway mutants affect visual physiology and brain function besides growth, lipid, and carbohydrate metabolism. Diabetes. 2011;60:1632-6 pubmed publisher..This is significant because flies have an open circulatory system without microvasculature and can be studied without the complications of vascular defects. ..
- Tseng A, Tapon N, Kanda H, Cigizoglu S, Edelmann L, Pellock B, et al. Capicua regulates cell proliferation downstream of the receptor tyrosine kinase/ras signaling pathway. Curr Biol. 2007;17:728-33 pubmed..Thus, the DNA-binding protein Cic is a key downstream component in the pathway by which Ras regulates growth in imaginal discs. ..
- Francis D, Ghabrial A. Compensatory branching morphogenesis of stalk cells in the Drosophila trachea. Development. 2015;142:2048-57 pubmed publisher..This compensatory branching also occurs in response to injury, with damaged terminal cells being rapidly invaded by their stalk cell neighbor. ..
- TakÃ¡ts S, Varga Ã, Pircs K, JuhÃ¡sz G. Loss of Drosophila Vps16A enhances autophagosome formation through reduced Tor activity. Autophagy. 2015;11:1209-15 pubmed publisher..Tor reactivation by overexpression of Rheb suppresses autophagosome formation and restores growth and developmental timing in these animals...
- Nagarajan S, Grewal S. An investigation of nutrient-dependent mRNA translation in Drosophila larvae. Biol Open. 2014;3:1020-31 pubmed publisher..These findings indicate that nutrient control of mRNA translation in larvae is more complex than simply amino acid activation of insulin and TOR signaling. ..
- Devorkin L, Go N, Hou Y, Moradian A, Morin G, Gorski S. The Drosophila effector caspase Dcp-1 regulates mitochondrial dynamics and autophagic flux via SesB. J Cell Biol. 2014;205:477-92 pubmed publisher..These data reveal a new mitochondrial-associated molecular link between nonapoptotic caspase function and autophagy regulation in vivo. ..
- Natarajan R, Trivedi Vyas D, Wairkar Y. Tuberous sclerosis complex regulates Drosophila neuromuscular junction growth via the TORC2/Akt pathway. Hum Mol Genet. 2013;22:2010-23 pubmed publisher..complex, consisting of Tsc1 and Tsc2 proteins, regulates the activity of the TOR (target of rapamycin) complex via Rheb, a small GTPase. TOR, an atypical serine/threonine kinase, forms two distinct complexes TORC1 and TORC2...
- Danielsen E, Moeller M, Yamanaka N, Ou Q, Laursen J, Soenderholm C, et al. A Drosophila Genome-Wide Screen Identifies Regulators of Steroid Hormone Production and Developmental Timing. Dev Cell. 2016;37:558-70 pubmed publisher..These results reveal genes regulating steroidogenesis during development that likely modulate disease mechanisms. ..
- Yaniv S, Issman Zecharya N, Oren Suissa M, Podbilewicz B, Schuldiner O. Axon regrowth during development and regeneration following injury share molecular mechanisms. Curr Biol. 2012;22:1774-82 pubmed publisher..Due to the involvement of the TOR pathway in axon regeneration following injury, our results also suggests that developmental regrowth shares common molecular mechanisms with regeneration following injury. ..