Genomes and Genes
Gene Symbol: chico
Alias: BcDNA.GH11263, BcDNA:GH11263, CG5686, CHICO, Chico, Dmel\CG5686, IRS, IRS/chico, anon-WO0078940.1, anon-WO0078940.4, chic, dIRS, fs(2)4, fs(2)ry4, chico, CG5686-PA, CG5686-PB, CG5686-PC, chico-PA, chico-PB, chico-PC, flipper, insulin receptor substrate, insulin-like receptor substrate
Species: fruit fly
- Shingleton A, Das J, Vinicius L, Stern D. The temporal requirements for insulin signaling during development in Drosophila. PLoS Biol. 2005;3:e289 pubmed..We hypothesize that the insulin-signaling pathway controls such diverse effects as total developmental time, total body size and organ size through its effects on the rate of cell growth, and proliferation in different organs. ..
- Yamamoto R, Tatar M. Insulin receptor substrate chico acts with the transcription factor FOXO to extend Drosophila lifespan. Aging Cell. 2011;10:729-32 pubmed publisher..Here, we conduct genetic epistasis analysis to determine whether foxo is required for chico mutants (insulin receptor substrate) to reduce age-specific mortality and thus extend lifespan...
- Richard D, Rybczynski R, Wilson T, Wang Y, Wayne M, Zhou Y, et al. Insulin signaling is necessary for vitellogenesis in Drosophila melanogaster independent of the roles of juvenile hormone and ecdysteroids: female sterility of the chico1 insulin signaling mutation is autonomous to the ovary. J Insect Physiol. 2005;51:455-64 pubmed..However, female sterility of an insulin/IGF-like signaling mutant (chico(1)) of D...
- Giannakou M, Goss M, Jacobson J, Vinti G, Leevers S, Partridge L. Dynamics of the action of dFOXO on adult mortality in Drosophila. Aging Cell. 2007;6:429-38 pubmed..The decreased mortality and increased lifespan of dFOXO overexpressing flies was uncoupled from any effect on female fecundity and from expression levels of Drosophila insulin-like peptides in the brain. ..
- Wong R, Piper M, Wertheim B, Partridge L. Quantification of food intake in Drosophila. PLoS ONE. 2009;4:e6063 pubmed publisher..that alterations in food intake are not induced by dietary restriction or by a null mutation of the fly insulin receptor substrate chico...
- Hsu H, LaFever L, Drummond Barbosa D. Diet controls normal and tumorous germline stem cells via insulin-dependent and -independent mechanisms in Drosophila. Dev Biol. 2008;313:700-12 pubmed..Moreover, the retained ability of GSC tumors to respond to diet parallels the long known connections between diet, insulin signaling, and cancer risk in humans. ..
- Honegger B, Galic M, Kohler K, Wittwer F, Brogiolo W, Hafen E, et al. Imp-L2, a putative homolog of vertebrate IGF-binding protein 7, counteracts insulin signaling in Drosophila and is essential for starvation resistance. J Biol. 2008;7:10 pubmed publisher..Given that Imp-L2 and the human tumor suppressor IGFBP-7 show sequence homology in their carboxy-terminal immunoglobulin-like domains, we suggest that their common precursor was an ancestral insulin-binding protein. ..
- Wu Q, Brown M. Signaling and function of insulin-like peptides in insects. Annu Rev Entomol. 2006;51:1-24 pubmed
- 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. ..
- Partridge L, Gems D, Withers D. Sex and death: what is the connection?. Cell. 2005;120:461-72 pubmed..Understanding the molecular basis of the cost of reproduction will be informed by elucidation of the mechanisms by which DR and IIS affect these two traits. ..
- Corl A, Rodan A, Heberlein U. Insulin signaling in the nervous system regulates ethanol intoxication in Drosophila melanogaster. Nat Neurosci. 2005;8:18-9 pubmed..These findings suggest a previously unknown role for this highly conserved pathway in regulating the behavioral responses to an addictive drug. ..
- Naganos S, Horiuchi J, Saitoe M. Mutations in the Drosophila insulin receptor substrate, CHICO, impair olfactory associative learning. Neurosci Res. 2012;73:49-55 pubmed publisherCHICO, the Drosophila homolog of vertebrate insulin receptor substrate (IRS), mediates insulin/insulin-like growth factor signaling (IIS), and reductions in chico severely disrupt cell growth and proliferation...
- Amcheslavsky A, Jiang J, Ip Y. Tissue damage-induced intestinal stem cell division in Drosophila. Cell Stem Cell. 2009;4:49-61 pubmed publisher..By using this newly established system of intestinal stem cell proliferation and tissue regeneration, we find that the insulin receptor signaling pathway is required for intestinal stem cell division. ..
- Bohni R, Riesgo Escovar J, Oldham S, Brogiolo W, Stocker H, Andruss B, et al. Autonomous control of cell and organ size by CHICO, a Drosophila homolog of vertebrate IRS1-4. Cell. 1999;97:865-75 pubmedThe control of growth is fundamental to the developing metazoan. Here, we show that CHICO, a Drosophila homolog of vertebrate IRS1-4, plays an essential role in the control of cell size and growth...
- Stocker H, Andjelkovic M, Oldham S, Laffargue M, Wymann M, Hemmings B, et al. Living with lethal PIP3 levels: viability of flies lacking PTEN restored by a PH domain mutation in Akt/PKB. Science. 2002;295:2088-91 pubmed..Thus, Akt appears to be the only critical target activated by increased PIP3 concentrations in Drosophila. ..
- Oldham S, Montagne J, Radimerski T, Thomas G, Hafen E. Genetic and biochemical characterization of dTOR, the Drosophila homolog of the target of rapamycin. Genes Dev. 2000;14:2689-94 pubmed..These results are consistent with dTOR residing on a parallel amino acid sensing pathway. ..
- 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..Our observations suggest that TSC1/2 and Rheb have different effects on the activity of TORC1 and -2, further supporting the complexity of TOR regulation. ..
- Song W, Ren D, Li W, Jiang L, Cho K, Huang P, et al. SH2B regulation of growth, metabolism, and longevity in both insects and mammals. Cell Metab. 2010;11:427-37 pubmed publisher..Here, we identified dSH2B as the Drosophila homolog of SH2B1. dSH2B bound to Chico and directly promoted insulin-like signaling...
- Tatar M, Yin C. Slow aging during insect reproductive diapause: why butterflies, grasshoppers and flies are like worms. Exp Gerontol. 2001;36:723-38 pubmed..elegans daf-2. We propose neuroendocrine control of reproductive diapause in D. melanogaster that includes phenotypic plasticity for rates of senescence. ..
- Goberdhan D, Paricio N, Goodman E, Mlodzik M, Wilson C. Drosophila tumor suppressor PTEN controls cell size and number by antagonizing the Chico/PI3-kinase signaling pathway. Genes Dev. 1999;13:3244-58 pubmed..to the Drosophila Class I phosphatidylinositol 3-kinase, Dp110, and its upstream activator Chico, an insulin receptor substrate homolog...
- Pan D, Dong J, Zhang Y, Gao X. Tuberous sclerosis complex: from Drosophila to human disease. Trends Cell Biol. 2004;14:78-85 pubmed..Here, we review these exciting developments with an emphasis on Drosophila studies and discuss how Drosophila can be a powerful model system for an understanding of the molecular mechanisms of the activity of human disease genes. ..
- Choi N, Lucchetta E, Ohlstein B. Nonautonomous regulation of Drosophila midgut stem cell proliferation by the insulin-signaling pathway. Proc Natl Acad Sci U S A. 2011;108:18702-7 pubmed publisher..These results suggest that ISCs can indirectly sense changes in nutrient and insulin levels through contact with their daughters and reveal a mechanism that could link physiological changes in tissue growth to stem cell proliferation...
- Drummond Barbosa D, Spradling A. Stem cells and their progeny respond to nutritional changes during Drosophila oogenesis. Dev Biol. 2001;231:265-78 pubmed
- Werz C, Kohler K, Hafen E, Stocker H. The Drosophila SH2B family adaptor Lnk acts in parallel to chico in the insulin signaling pathway. PLoS Genet. 2009;5:e1000596 pubmed publisher..phosphoinositide 3-kinase (PI3K) in the IIS cascade, at the same level as chico (encoding the single fly insulin receptor substrate [IRS] homolog)...
- Hsu H, Drummond Barbosa D. Insulin levels control female germline stem cell maintenance via the niche in Drosophila. Proc Natl Acad Sci U S A. 2009;106:1117-21 pubmed publisher..These results underscore the importance of systemic factors for the regulation of stem cell niches and, thereby, of stem cell numbers. ..
- Libert S, Chao Y, Zwiener J, Pletcher S. Realized immune response is enhanced in long-lived puc and chico mutants but is unaffected by dietary restriction. Mol Immunol. 2008;45:810-7 pubmed..system in Drosophila carrying the longevity extending mutations puc (JNK signaling pathway, stress response) and chico (insulin signaling pathway), as well as animals subjected to dietary restriction (DR), which also extends lifespan...
- Bjedov I, Toivonen J, Kerr F, Slack C, Jacobson J, Foley A, et al. Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster. Cell Metab. 2010;11:35-46 pubmed publisher..Rapamycin could increase life span of weak insulin/Igf signaling (IIS) pathway mutants and of flies with life span maximized by dietary restriction, indicating additional mechanisms. ..
- Kenyon C. The plasticity of aging: insights from long-lived mutants. Cell. 2005;120:449-60 pubmed..Many mutations affecting longevity pathways delay age-related disease, and the molecular analysis of these pathways is leading to a mechanistic understanding of how these two processes--aging and disease susceptibility--are linked. ..
- Huang H, Potter C, Tao W, Li D, Brogiolo W, Hafen E, et al. PTEN affects cell size, cell proliferation and apoptosis during Drosophila eye development. Development. 1999;126:5365-72 pubmed
- Oldham S, Stocker H, Laffargue M, Wittwer F, Wymann M, Hafen E. The Drosophila insulin/IGF receptor controls growth and size by modulating PtdInsP(3) levels. Development. 2002;129:4103-9 pubmed..We show that in Drosophila mutating the consensus binding site for the Ras pathway adaptor Drk/Grb2 in Chico/IRS does not interfere with growth whereas mutating the binding sites of the PI 3-kinase adaptor p60 completely ..
- Pflieger D, Jünger M, Muller M, Rinner O, Lee H, Gehrig P, et al. Quantitative proteomic analysis of protein complexes: concurrent identification of interactors and their state of phosphorylation. Mol Cell Proteomics. 2008;7:326-46 pubmed..of samples immunopurified from Drosophila melanogaster cells expressing an epitope-tagged form of the insulin receptor substrate homologue Chico...
- Tu M, Epstein D, Tatar M. The demography of slow aging in male and female Drosophila mutant for the insulin-receptor substrate homologue chico. Aging Cell. 2002;1:75-80 pubmed..this sex-difference, we conducted a large-scale demographic study with three new isogenic strains of alleles at chico, the insulin-receptor substrate homologue...
- Day S, Lawrence P. Measuring dimensions: the regulation of size and shape. Development. 2000;127:2977-87 pubmed..We discuss a hypothesis that the local steepness of a morphogen gradient is a measure of length in one axis, a measure that is used to determine whether there will be net growth or not. ..
- Clancy D, Gems D, Harshman L, Oldham S, Stocker H, Hafen E, et al. Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein. Science. 2001;292:104-6 pubmedThe Drosophila melanogaster gene chico encodes an insulin receptor substrate that functions in an insulin/insulin-like growth factor (IGF) signaling pathway...
- Radimerski T, Montagne J, Rintelen F, Stocker H, van der Kaay J, Downes C, et al. dS6K-regulated cell growth is dPKB/dPI(3)K-independent, but requires dPDK1. Nat Cell Biol. 2002;4:251-5 pubmed..Effectors of this pathway include Chico (the insulin receptor substrate homologue), dPI(3)K, dPKB, dPTEN, and dS6K...
- Wittwer F, Jaquenoud M, Brogiolo W, Zarske M, Wüstemann P, Fernandez R, et al. Susi, a negative regulator of Drosophila PI3-kinase. Dev Cell. 2005;8:817-27 pubmed..The fact that Susi is expressed in a circadian rhythm, with highest levels during the night, suggests that Susi attenuates insulin signaling during the fasting period. ..
- 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. ..
- Luo X, Puig O, Hyun J, Bohmann D, Jasper H. Foxo and Fos regulate the decision between cell death and survival in response to UV irradiation. EMBO J. 2007;26:380-90 pubmed..These data suggest that integrating stress and survival signals through Foxo drives the decision between cell death and repair of damaged cells in vivo. ..
- Wessells R, Fitzgerald E, Cypser J, Tatar M, Bodmer R. Insulin regulation of heart function in aging fruit flies. Nat Genet. 2004;36:1275-81 pubmed..systemic levels of insulin-like peptides are reduced and by mutations of the only receptor, InR, or its substrate, chico. Moreover, interfering with InR signaling exclusively in the heart, by overexpressing the phosphatase dPTEN or the ..
- Towers P, Sattelle D. A Drosophila melanogaster cell line (S2) facilitates post-genome functional analysis of receptors and ion channels. Bioessays. 2002;24:1066-73 pubmed..In addition, many useful orthologues of human disease genes are emerging from the Drosophila genome and the study of their functions and interactions is another area for postgenome applications of S2 cell lines. ..
- Roussel M. The Cold Spring Harbor Laboratory meeting on tyrosine phosphorylation and cell signaling. Cold Spring Harbor, NY, USA, May 12-16, 1999. Biochim Biophys Acta. 2000;1470:R17-20 pubmed
- Partridge L, Alic N, Bjedov I, Piper M. Ageing in Drosophila: the role of the insulin/Igf and TOR signalling network. Exp Gerontol. 2011;46:376-81 pubmed publisher..Reduced IIS can act acutely to lower death rate, implying that it may ameliorate the effects of ageing-related damage, rather than preventing it. ..
- Jaklevic B, Uyetake L, Lemstra W, Chang J, Leary W, Edwards A, et al. Contribution of growth and cell cycle checkpoints to radiation survival in Drosophila. Genetics. 2006;174:1963-72 pubmed..or onset of pupariation) or inhibition of growth factor signaling and downstream targets (by mutations in cdk4, chico, or dmyc) reduced the radiation survival of larvae...
- 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. ..
- Helfand S, Rogina B. Molecular genetics of aging in the fly: is this the end of the beginning?. Bioessays. 2003;25:134-41 pubmed
- Dickson B. Development. Wiring the brain with insulin. Science. 2003;300:440-1 pubmed
- Song J, Wu L, Chen Z, Kohanski R, Pick L. Axons guided by insulin receptor in Drosophila visual system. Science. 2003;300:502-5 pubmed..DInR functions as a guidance receptor for the adapter protein Dock/Nck. This function is independent of Chico, the Drosophila insulin receptor substrate (IRS) homolog.
- Read R, Bach E, Cagan R. Drosophila C-terminal Src kinase negatively regulates organ growth and cell proliferation through inhibition of the Src, Jun N-terminal kinase, and STAT pathways. Mol Cell Biol. 2004;24:6676-89 pubmed..In particular, blockade of STAT function in dCsk mutants severely reduced Src-dependent overgrowth and activated apoptosis of mutant tissue. Our data provide in vivo evidence that Src activity requires JNK and STAT function. ..
- Pritchett T, McCall K. Role of the insulin/Tor signaling network in starvation-induced programmed cell death in Drosophila oogenesis. Cell Death Differ. 2012;19:1069-79 pubmed publisher..Furthermore, starvation-induced PCD is regulated by Tor signaling converging with the canonical insulin signaling pathway. ..
- Naganos S, Ueno K, Horiuchi J, Saitoe M. Learning defects in Drosophila growth restricted chico mutants are caused by attenuated adenylyl cyclase activity. Mol Brain. 2016;9:37 pubmed publisher..In Drosophila, chico encodes the only insulin receptor substrate. Similar to other animal models of IUGR, chico mutants have defects in global growth and associative ..
- Wang B, Goode J, Best J, Meltzer J, Schilman P, Chen J, et al. The insulin-regulated CREB coactivator TORC promotes stress resistance in Drosophila. Cell Metab. 2008;7:434-44 pubmed publisher..As disruption of insulin signaling also augmented TORC activity in adult flies, our results illustrate the importance of an insulin-regulated pathway that functions in the brain to maintain energy balance. ..
- Gumienny T, Padgett R. A small issue addressed. Bioessays. 2003;25:305-8 pubmed..elegans, the TGFbeta-like pathway acts in the hypodermis to regulate cell size and consequently body size.1 This finding is an exciting step in discovering the molecular mechanisms that control cell and body size. ..
- Murillo Maldonado J, Zeineddine F, Stock R, THACKERAY J, Riesgo Escovar J. Insulin receptor-mediated signaling via phospholipase C-? regulates growth and differentiation in Drosophila. PLoS ONE. 2011;6:e28067 pubmed publisher..Overall, our results provide evidence that PLC-? acts during development at a time when growth ends and differentiation begins, and is important for proper coordination of these two processes. ..
- Xu K, Zheng X, Sehgal A. Regulation of feeding and metabolism by neuronal and peripheral clocks in Drosophila. Cell Metab. 2008;8:289-300 pubmed publisher..We propose that the input of neuronal clocks and clocks in metabolic tissues is coordinated to provide effective energy homeostasis...
- Bai H, Kang P, Hernandez A, Tatar M. Activin signaling targeted by insulin/dFOXO regulates aging and muscle proteostasis in Drosophila. PLoS Genet. 2013;9:e1003941 pubmed publisher..Reduced insulin secretion from the brain may subsequently reinforce longevity assurance through decreased systemic insulin/IGF signaling. ..
- Knight A, Yan X, Hamamichi S, Ajjuri R, Mazzulli J, Zhang M, et al. The glycolytic enzyme, GPI, is a functionally conserved modifier of dopaminergic neurodegeneration in Parkinson's models. Cell Metab. 2014;20:145-57 pubmed publisher..Collectively, these results support glucose metabolism as a conserved functional node at the intersection of proteostasis and neurodegeneration. ..
- Hsu H, Drummond Barbosa D. Insulin signals control the competence of the Drosophila female germline stem cell niche to respond to Notch ligands. Dev Biol. 2011;350:290-300 pubmed publisher..These results are potentially relevant to many systems in which Notch signaling modulates stem cells and demonstrate that complex interactions between local and systemic signals are required for proper stem cell niche function. ..
- Alvarez Ponce D, Aguade M, Rozas J. Network-level molecular evolutionary analysis of the insulin/TOR signal transduction pathway across 12 Drosophila genomes. Genome Res. 2009;19:234-42 pubmed publisher..Our results clearly indicate that the levels of functional constraint do depend on the position of the proteins in the pathway and, consequently, the architecture of the pathway constrains gene sequence evolution. ..
- 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. ..
- Scherfer C, Han V, Wang Y, Anderson A, Galko M. Autophagy drives epidermal deterioration in a Drosophila model of tissue aging. Aging (Albany NY). 2013;5:276-87 pubmed..Because the aging readout we introduce here has an early onset and is easily visualized, genetic dissection using our model should identify other novel mechanisms by which lifespan genes feed into tissue-specific aging. ..