Genomes and Genes
Gene Symbol: Tsc1
Alias: CG6147, Dmel\CG6147, TSC, TSC1, dTSC, dTSC-1, dTSC1, dTsc1, dtsc1, rocky, tsc1, Tsc1, CG6147-PA, TTuberous sclerosis complex 1, Tsc1-PA, hamartin, jolly green giant, rocky, tuberous sclerosis 1, tuberous sclerosis complex 1, tuberous sclerosis complex protein 1
Species: fruit fly
- Reiling J, Hafen E. The hypoxia-induced paralogs Scylla and Charybdis inhibit growth by down-regulating S6K activity upstream of TSC in Drosophila. Genes Dev. 2004;18:2879-92 pubmed..Together, genetic and biochemical analysis places Scylla/Charybdis downstream of PKB and upstream of TSC. Furthermore, we show that scylla and charybdis are induced under hypoxic conditions and that scylla is a target of ..
- Hietakangas V, Cohen S. Re-evaluating AKT regulation: role of TOR complex 2 in tissue growth. Genes Dev. 2007;21:632-7 pubmed..Thus, TORC2 acts as a rheostat to broaden the range of AKT signaling at the high end of its range. ..
- Demontis F, Perrimon N. Integration of Insulin receptor/Foxo signaling and dMyc activity during muscle growth regulates body size in Drosophila. Development. 2009;136:983-93 pubmed publisher..Thus, maximal dMyc transcriptional activity depends on InR to control muscle mass, which in turn induces a systemic behavioral response to allocate body size and proportions. ..
- Udan R, Kango Singh M, Nolo R, Tao C, Halder G. Hippo promotes proliferation arrest and apoptosis in the Salvador/Warts pathway. Nat Cell Biol. 2003;5:914-20 pubmed..We find that Sav binds to a regulatory domain of Hpo that is essential for its function, indicating that Hpo acts together with Sav and Wts in a signalling module that coordinately regulates cell proliferation and apoptosis. ..
- 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 pubmedMutations in the TSC1 or TSC2 genes cause tuberous sclerosis, a benign tumour syndrome in humans...
- 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..Here, we further characterize this phenomenon. We show that tuberous sclerosis complex 1 mutations cause increased FOXO levels, resulting in elevated expression of FOXO-regulated genes, some ..
- Kapahi P, Zid B, Harper T, Koslover D, Sapin V, Benzer S. Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr Biol. 2004;14:885-90 pubmed..We find that overexpression of dTsc1, dTsc2, or dominant-negative forms of dTOR or dS6K all cause lifespan extension...
- 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. ..
- 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...
- Gao X, Zhang Y, Arrazola P, Hino O, Kobayashi T, Yeung R, et al. Tsc tumour suppressor proteins antagonize amino-acid-TOR signalling. Nat Cell Biol. 2002;4:699-704 pubmed..Here, we show that tuberous sclerosis 1 (Tsc1) and Tsc2, tumour suppressors that are responsible for the tuberous sclerosis syndrome, antagonize ..
- Schleich S, Teleman A. Akt phosphorylates both Tsc1 and Tsc2 in Drosophila, but neither phosphorylation is required for normal animal growth. PLoS ONE. 2009;4:e6305 pubmed publisher..Since Drosophila Tsc1, the obligate partner of Tsc2, has an Akt phosphorylation motif that is not conserved in mammals, we investigate ..
- Geminard C, Rulifson E, Leopold P. Remote control of insulin secretion by fat cells in Drosophila. Cell Metab. 2009;10:199-207 pubmed publisher..Thus, the availability of nutrients is remotely sensed in fat body cells and conveyed to the brain IPCs by a humoral signal controlling ILP release. ..
- Zhang Y, Billington C, Pan D, Neufeld T. Drosophila target of rapamycin kinase functions as a multimer. Genetics. 2006;172:355-62 pubmed..mutations in the HEAT and kinase domains can dominantly interfere with wild-type TOR function in cells lacking TSC1 or TSC2...
- LaFever L, Feoktistov A, Hsu H, Drummond Barbosa D. Specific roles of Target of rapamycin in the control of stem cells and their progeny in the Drosophila ovary. Development. 2010;137:2117-26 pubmed publisher..These results uncover specific TOR functions in the control of stem cells versus their differentiating progeny, and reveal parallels between Drosophila and mammalian follicle growth. ..
- 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..Here, we report that Tuberous Sclerosis Complex 1 (TSC1), a well-established tumor suppressor that regulates cell size, is an important regulator of ..
- 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. ..
- Radimerski T, Montagne J, Hemmings Mieszczak M, Thomas G. Lethality of Drosophila lacking TSC tumor suppressor function rescued by reducing dS6K signaling. Genes Dev. 2002;16:2627-32 pubmed..More importantly, we demonstrate that reducing dS6K signaling rescues early larval lethality associated with loss of dTsc1/2 function, arguing that the S6K pathway is a promising target for the treatment of TSC.
- Cheng L, Bailey A, Leevers S, Ragan T, Driscoll P, Gould A. Anaplastic lymphoma kinase spares organ growth during nutrient restriction in Drosophila. Cell. 2011;146:435-47 pubmed publisher..Together, these findings identify a brain-sparing mechanism that shares some regulatory features with the starvation-resistant growth programs of mammalian tumors. ..
- 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..Thus, in cells lacking TOR, autophagy plays a protective role that is dominant over its potential role as a growth suppressor. ..
- Lee J, Koh H, Kim M, Park J, Lee S, Lee S, et al. JNK pathway mediates apoptotic cell death induced by tumor suppressor LKB1 in Drosophila. Cell Death Differ. 2006;13:1110-22 pubmed..Collectively, our studies unprecedentedly elucidate JNK as the downstream mediator of the LKB1-dependent apoptosis, and provide a new paradigm for understanding the diverse LKB1 functions in vivo. ..
- Colombani J, Raisin S, Pantalacci S, Radimerski T, Montagne J, Leopold P. A nutrient sensor mechanism controls Drosophila growth. Cell. 2003;114:739-49 pubmed..This involves TSC/TOR signaling in the fat body, and a remote inhibition of organismal growth via local repression of PI3-kinase ..
- Pan D, Dong J, Zhang Y, Gao X. Tuberous sclerosis complex: from Drosophila to human disease. Trends Cell Biol. 2004;14:78-85 pubmed..This disease is caused by mutations in the TSC1 or TSC2 tumor suppressor genes; the molecular mechanisms underlying the activity of these have long been elusive...
- Murthy V, Han S, Beauchamp R, Smith N, Haddad L, Ito N, et al. Pam and its ortholog highwire interact with and may negatively regulate the TSC1.TSC2 complex. J Biol Chem. 2004;279:1351-8 pubmed..Sclerosis Complex (TSC) is an autosomal dominant disorder associated with mutations in TSC1, which codes for hamartin, or TSC2, which codes for tuberin...
- Potter C, Pedraza L, Xu T. Akt regulates growth by directly phosphorylating Tsc2. Nat Cell Biol. 2002;4:658-65 pubmed..growth by phosphorylating the tuberous sclerosis complex 2 (Tsc2) tumour suppressor and inhibiting formation of a Tsc1-Tsc2 complex...
- 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. ..
- Jünger M, Rintelen F, Stocker H, Wasserman J, Végh M, Radimerski T, et al. The Drosophila forkhead transcription factor FOXO mediates the reduction in cell number associated with reduced insulin signaling. J Biol. 2003;2:20 pubmed..We propose that in response to cellular stresses, such as nutrient deprivation or increased levels of reactive oxygen species, dFOXO is activated and inhibits growth through the action of target genes such as d4E-BP. ..
- Layalle S, Arquier N, Leopold P. The TOR pathway couples nutrition and developmental timing in Drosophila. Dev Cell. 2008;15:568-77 pubmed publisher..In conclusion, the PG uses TOR signaling to couple nutritional input with ecdysone production and developmental timing. ..
- Sun P, Quan Z, Zhang B, Wu T, Xi R. TSC1/2 tumour suppressor complex maintains Drosophila germline stem cells by preventing differentiation. Development. 2010;137:2461-9 pubmed publisherTuberous sclerosis complex human disease gene products TSC1 and TSC2 form a functional complex that negatively regulates target of rapamycin (TOR), an evolutionarily conserved kinase that plays a central role in cell growth and metabolism...
- Bateman J, McNeill H. Temporal control of differentiation by the insulin receptor/tor pathway in Drosophila. Cell. 2004;119:87-96 pubmed..In a screen for patterning mutants, we isolated alleles of tsc1, a component of the insulin receptor (InR) growth control pathway...
- 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. ..
- Manning B, Cantley L. Rheb fills a GAP between TSC and TOR. Trends Biochem Sci. 2003;28:573-6 pubmedThere has been much interest in determining the molecular and cellular functions of hamartin and tuberin, which are encoded by the genes TSC1 and TSC2 that are mutated in the tuberous sclerosis complex disease...
- Amcheslavsky A, Ito N, Jiang J, Ip Y. Tuberous sclerosis complex and Myc coordinate the growth and division of Drosophila intestinal stem cells. J Cell Biol. 2011;193:695-710 pubmed publisher..We demonstrate in this paper that the tuberous sclerosis complex (TSC) plays a critical role in balancing ISC growth and division...
- Yang Q, Inoki K, Kim E, Guan K. TSC1/TSC2 and Rheb have different effects on TORC1 and TORC2 activity. Proc Natl Acad Sci U S A. 2006;103:6811-6 pubmed..Furthermore, tuberous sclerosis complex 1 (TSC1) and TSC2, which are negative regulators of Rheb, have negative and positive effects on TORC1 and ..
- Gao X, Pan D. TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth. Genes Dev. 2001;15:1383-92 pubmedTuberous sclerosis is a human disease caused by mutations in the TSC1 or the TSC2 tumor suppressor gene...
- Marshall L, Rideout E, Grewal S. Nutrient/TOR-dependent regulation of RNA polymerase III controls tissue and organismal growth in Drosophila. EMBO J. 2012;31:1916-30 pubmed publisher..Thus, stimulation of Pol III is a key downstream effector of TOR in the control of cellular and systemic growth. ..
- Teleman A, Chen Y, Cohen S. Drosophila Melted modulates FOXO and TOR activity. Dev Cell. 2005;9:271-81 pubmed..Here, we identify Melted as a new modulator of this pathway in Drosophila. Melted interacts with both Tsc1 and FOXO and can recruit these proteins to the cell membrane...
- 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 publisherMutations in either of the genes encoding the tuberous sclerosis complex (TSC), TSC1 and TSC2, result in a multisystem tumor disorder characterized by lesions with unusual lineage expression patterns...
- 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..Our genetic and biochemical analyses suggest that Rheb functions downstream of the tumour suppressors Tsc1 (tuberous sclerosis 1)-Tsc2 in the TOR (target of rapamycin) signalling pathway to control growth, and that a major effector of ..
- 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..Tuberous sclerosis (TSC) is a benign tumour syndrome caused by mutations in either TSC1 or TSC2 tumour suppressor genes...
- Jorgensen P, Tyers M. How cells coordinate growth and division. Curr Biol. 2004;14:R1014-27 pubmed..Recently, genetic screens in Drosophila and functional genomics approaches in yeast have macheted into the thicket of cell size control. ..
- Tapon N, Ito N, Dickson B, Treisman J, Hariharan I. The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation. Cell. 2001;105:345-55 pubmed..inherited human disease tuberous sclerosis, characterized by hamartomatous tumors, results from mutations in either TSC1 or TSC2. We have characterized mutations in the Drosophila Tsc1 and Tsc2/gigas genes...
- Potter C, Huang H, Xu T. Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size. Cell. 2001;105:357-68 pubmed..We have isolated a mutation in the Drosophila homolog of TSC1 (Tsc1). Cells mutant for Tsc1 are dramatically increased in size yet differentiate normally...
- Delalle I, Pfleger C, Buff E, Lueras P, Hariharan I. Mutations in the Drosophila orthologs of the F-actin capping protein alpha- and beta-subunits cause actin accumulation and subsequent retinal degeneration. Genetics. 2005;171:1757-65 pubmed..In its absence, cells progressively accumulate actin filaments and eventually die. A possible role for their human orthologs in neurodegenerative disease merits further investigation. ..
- Huang Z, Ren S, Jiang Y, Wang T. PINK1 and Parkin cooperatively protect neurons against constitutively active TRP channel-induced retinal degeneration in Drosophila. Cell Death Dis. 2016;7:e2179 pubmed publisher..In addition, the results demonstrated that maintaining mitochondrial homeostasis via PINK1/Parkin-dependent mitochondrial quality control can potentially alleviate cell death in a wide range of neurodegenerative diseases. ..
- Nuzhdin S, Brisson J, Pickering A, Wayne M, Harshman L, McIntyre L. Natural genetic variation in transcriptome reflects network structure inferred with major effect mutations: insulin/TOR and associated phenotypes in Drosophila melanogaster. BMC Genomics. 2009;10:124 pubmed publisher..In summary, our results question the assertion of the 'sparse' nature of genetic networks, while validating and extending candidate gene approaches in the analyses of complex traits. ..
- Avet Rochex A, Carvajal N, Christoforou C, Yeung K, Maierbrugger K, Hobbs C, et al. Unkempt is negatively regulated by mTOR and uncouples neuronal differentiation from growth control. PLoS Genet. 2014;10:e1004624 pubmed publisher..of unk and hdc completely suppresses the precocious neuronal differentiation phenotype caused by loss of Tsc1. Thus, Unk and Hdc are the first neurogenic components of the InR/mTOR pathway to be identified...
- Potter C, Xu T. Mechanisms of size control. Curr Opin Genet Dev. 2001;11:279-86 pubmed..The mechanisms of organ size control could also be critical targets for evolutionary events or disease processes such as tumorigenesis. ..
- Zhang T, Liao Y, Hsu F, Zhang R, Searle J, Pei X, et al. Hyperactivated Wnt signaling induces synthetic lethal interaction with Rb inactivation by elevating TORC1 activities. PLoS Genet. 2014;10:e1004357 pubmed publisher..These results suggest that elevated TORC1 activity and metabolic stress underpin the evolutionarily conserved synthetic lethal interaction between hyperactivated Wnt signaling and inactivated Rb tumor suppressor. ..
- Benmimoun B, Polesello C, Waltzer L, Haenlin M. Dual role for Insulin/TOR signaling in the control of hematopoietic progenitor maintenance in Drosophila. Development. 2012;139:1713-7 pubmed publisher..Hence, our study highlights the role of the IIS/TOR pathways in orchestrating hematopoietic progenitor fate and links blood cell fate to nutritional status. ..
- Denton D, Chang T, Nicolson S, Shravage B, Simin R, Baehrecke E, et al. Relationship between growth arrest and autophagy in midgut programmed cell death in Drosophila. Cell Death Differ. 2012;19:1299-307 pubmed publisher..Despite the roles of autophagy in both survival and death, our findings suggest that autophagy induction occurs in response to similar signals in both scenarios. ..
- Cai W, Wei Y, Jarnik M, Reich J, Lilly M. The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lysosome Function. PLoS Genet. 2016;12:e1006036 pubmed publisher..Taken together our data support the model that Wdr24 is a key effector of the GATOR2 complex, required for both TORC1 activation and the TORC1 independent regulation of lysosomes. ..
- 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..missing, or misguided dorsally in five double heterozygote combinations (;unf/+;axin/+, unf/+;Fps85D/+, ;unf/+;Tsc1/+, ;unf/+;Rheb/+, ;unf/+;msn/+)...
- 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..The TSC1/2 complex inhibits TOR signaling, acting as a tumor suppressor in vertebrates and regulating cell growth...
- 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. ..
- Leopold P. Neuronal differentiation: TOR and insulin receptor pathways set the tempo. Cell. 2004;119:4-5 pubmed..A recent study reveals a novel role for these pathways in controlling the timing of neuronal differentiation during Drosophila development, thus allowing a tight coordination between growth and differentiation programs. ..
- Yapici N, Zimmer M, Domingos A. Cellular and molecular basis of decision-making. EMBO Rep. 2014;15:1023-35 pubmed publisher..These studies interrogate decision-making about food, sexual behaviour, aggression or foraging strategies, and add molecular and cell biology understanding onto the consilience of brain and decision. ..
- Lam D, Shah S, de Castro I, Loh S, Martins L. Drosophila happyhour modulates JNK-dependent apoptosis. Cell Death Dis. 2010;1:e66 pubmed publisher..Together, our results show that hppy has a JNK-dependent proapoptotic function in Drosophila, which reinforces the hypothesis that MAP4K3 might act as tumour suppressor by regulating apoptosis in higher eukaryotes. ..
- Potter C, Tasic B, Russler E, Liang L, Luo L. The Q system: a repressible binary system for transgene expression, lineage tracing, and mosaic analysis. Cell. 2010;141:536-48 pubmed publisher..The Q system can be expanded to other uses in Drosophila and to any organism conducive to transgenesis...