Gene Symbol: Gclc
Description: Glutamate-cysteine ligase catalytic subunit
Alias: 2259, CG2259, DmGCLC, DmGCS, DmGCSh, Dmel\CG2259, GCL, GCLC, GCLc, GCSh, GclC, Gcs, Gcsh, gclc, Glutamate-cysteine ligase catalytic subunit, CG2259-PA, CG2259-PB, CG2259-PC, CG2259-PD, Gclc-PA, Gclc-PB, Gclc-PC, Gclc-PD, catalytic subunit of glutamate- cysteine ligase, gamma-Glutamylcysteine synthetase, gamma-Glutamylcysteine synthetase catalytic subunit, gamma-glutamylcysteine ligase, glutamate cysteine ligase, glutamate-cysteine ligase
Species: fruit fly
Products:     Gclc

Top Publications

  1. Fraser J, Saunders R, McLellan L. Drosophila melanogaster glutamate-cysteine ligase activity is regulated by a modifier subunit with a mechanism of action similar to that of the mammalian form. J Biol Chem. 2002;277:1158-65 pubmed
    ..D. melanogaster GCLC (DmGCLC) and the candidate DmGCLM were expressed separately in Escherichia coli, purified, mixed, and then subjected to ..
  2. Radyuk S, Gambini J, Borras C, Serna E, Klichko V, Vina J, et al. Age-dependent changes in the transcription profile of long-lived Drosophila over-expressing glutamate cysteine ligase. Mech Ageing Dev. 2012;133:401-13 pubmed publisher
    ..Functional clustering analysis of the transcriptome data revealed that biological processes affected by GCLc in young flies (10 days) were generally related to cell morphogenesis and differentiation, while those in older ..
  3. Hochmuth C, Biteau B, Bohmann D, Jasper H. Redox regulation by Keap1 and Nrf2 controls intestinal stem cell proliferation in Drosophila. Cell Stem Cell. 2011;8:188-99 pubmed publisher
    ..Our findings establish Keap1 and Nrf2 as a critical redox management system that regulates stem cell function in high-turnover tissues. ..
  4. Radyuk S, Rebrin I, Luchak J, Michalak K, Klichko V, Sohal R, et al. The catalytic subunit of Drosophila glutamate-cysteine ligase is a nucleocytoplasmic shuttling protein. J Biol Chem. 2009;284:2266-74 pubmed publisher
    ..The rate-limiting step in the de novo GSH biosynthesis pathway is catalyzed by glutamate cysteine ligase (GCL), a heterodimer, composed of a catalytic subunit (GCLc) and a modulatory subunit (GCLm)...
  5. Luchak J, Prabhudesai L, Sohal R, Radyuk S, Orr W. Modulating longevity in Drosophila by over- and underexpression of glutamate-cysteine ligase. Ann N Y Acad Sci. 2007;1119:260-73 pubmed
    ..span (up to 50%) was achieved in Drosophila melanogaster when the catalytic subunit of glutamate-cysteine ligase (GCLc) was overexpressed in neuronal tissue, while a moderate increase (up to 24%) was observed when the modulatory ..
  6. Orr W, Radyuk S, Prabhudesai L, Toroser D, Benes J, Luchak J, et al. Overexpression of glutamate-cysteine ligase extends life span in Drosophila melanogaster. J Biol Chem. 2005;280:37331-8 pubmed
    ..The GAL4-UAS binary transgenic system was used to generate flies overexpressing either the catalytic (GCLc) or modulatory (GCLm) subunit of this enzyme, in a global or neuronally targeted pattern...
  7. Fraser J, Kansagra P, Kotecki C, Saunders R, McLellan L. The modifier subunit of Drosophila glutamate-cysteine ligase regulates catalytic activity by covalent and noncovalent interactions and influences glutathione homeostasis in vivo. J Biol Chem. 2003;278:46369-77 pubmed
    ..Drosophila melanogaster GCL modifier subunit (DmGCLM) can form covalent interactions with the catalytic subunit (DmGCLC) and modify its activity...
  8. Rahman M, Sykiotis G, Nishimura M, Bodmer R, Bohmann D. Declining signal dependence of Nrf2-MafS-regulated gene expression correlates with aging phenotypes. Aging Cell. 2013;12:554-62 pubmed publisher
    ..The maintenance of acute stress resistance, motor function, and heart performance in aging flies overexpressing MafS supports a critical role for signal responsiveness of Nrf2 function in promoting youthful phenotypes. ..
  9. Wang C, Yolitz J, Alberico T, Laslo M, Sun Y, Wheeler C, et al. Cranberry interacts with dietary macronutrients to promote healthy aging in Drosophila. J Gerontol A Biol Sci Med Sci. 2014;69:945-54 pubmed publisher
    ..Our study reveals an interaction of cranberry with dietary macronutrients and stresses the importance of considering diet composition in designing interventions for promoting healthy aging. ..

More Information


  1. Saunders R, McLellan L. Molecular cloning of Drosophila gamma-glutamylcysteine synthetase by functional complementation of a yeast mutant. FEBS Lett. 2000;467:337-40 pubmed
    gamma-Glutamylcysteine synthetase (GCS) catalyses a critical, rate-limiting step in glutathione synthesis. In this study we describe the isolation and characterisation of a GCS cDNA (pDmGCS4.3...
  2. Beaver L, Klichko V, Chow E, Kotwica Rolinska J, Williamson M, Orr W, et al. Circadian regulation of glutathione levels and biosynthesis in Drosophila melanogaster. PLoS ONE. 2012;7:e50454 pubmed publisher
    ..We further demonstrate a rhythm in activity of glutamate cysteine ligase (GCL), the rate-limiting enzyme in glutathione biosynthesis...
  3. Klichko V, Chow E, Kotwica Rolinska J, Orr W, Giebultowicz J, Radyuk S. Aging alters circadian regulation of redox in Drosophila. Front Genet. 2015;6:83 pubmed publisher
    ..of the clock genes on expression of the catalytic (Gclc) and modulatory (Gclm) subunits comprising the glutamate cysteine ligase (GCL) holoenzyme...
  4. Barnes V, Bhat A, Unnikrishnan A, Heydari A, Arking R, Pile L. SIN3 is critical for stress resistance and modulates adult lifespan. Aging (Albany NY). 2014;6:645-60 pubmed
    ..Taken together, the data support a model whereby SIN3 regulates a gene expression program required for proper mitochondrial function and effective stress response during adulthood. ..
  5. de Aguiar L, Figueira F, Gottschalk M, da Rosa C. Glyphosate-based herbicide exposure causes antioxidant defence responses in the fruit fly Drosophila melanogaster. Comp Biochem Physiol C Toxicol Pharmacol. 2016;185-186:94-101 pubmed publisher
    ..In addition, the mRNA expression of antioxidant genes (i.e., keap1, sod, sod2, cat, irc, gclc, gclm, gss, trxt, trxr-1 and trxr-2) was evaluated via RT-PCR...
  6. Li X, Chatterjee N, Spirohn K, Boutros M, Bohmann D. Cdk12 Is A Gene-Selective RNA Polymerase II Kinase That Regulates a Subset of the Transcriptome, Including Nrf2 Target Genes. Sci Rep. 2016;6:21455 pubmed publisher
    ..We suggest that Cdk12 acts as a gene-selective Pol II kinase that engages a global shift in gene expression to switch cells from a metabolically active state to "stress-defence mode" when challenged by external stress. ..
  7. Mercer S, La Fontaine S, Warr C, Burke R. Reduced glutathione biosynthesis in Drosophila melanogaster causes neuronal defects linked to copper deficiency. J Neurochem. 2016;137:360-70 pubmed publisher
    ..RNA interference-mediated knockdown of the Glutamate-cysteine ligase catalytic subunit gene (Gclc) that encodes the rate-limiting enzyme in GSH biosynthesis was utilised to genetically deplete GSH levels...
  8. Lashmanova E, Proshkina E, Zhikrivetskaya S, Shevchenko O, Marusich E, Leonov S, et al. Fucoxanthin increases lifespan of Drosophila melanogaster and Caenorhabditis elegans. Pharmacol Res. 2015;100:228-41 pubmed publisher
    ..elegans were revealed only for fucoxanthin. In presence of carotenoids decreased flies' fecundity, increased spontaneous locomotor activity and resistance to oxidative stress were detected. ..
  9. López Del Amo V, Seco Cervera M, García Giménez J, Whitworth A, Pallardó F, Galindo M. Mitochondrial defects and neuromuscular degeneration caused by altered expression of Drosophila Gdap1: implications for the Charcot-Marie-Tooth neuropathy. Hum Mol Genet. 2015;24:21-36 pubmed publisher
  10. Sohal R, Forster M. Caloric restriction and the aging process: a critique. Free Radic Biol Med. 2014;73:366-82 pubmed publisher
    ..In such groups, CR lowers body temperature, rate of metabolism, and oxidant production and retards the age-related pro-oxidizing shift in the redox state. ..
  11. Mockett R, Nobles A. Lack of robustness of life extension associated with several single-gene P element mutations in Drosophila melanogaster. J Gerontol A Biol Sci Med Sci. 2013;68:1157-69 pubmed publisher
    ..Transgenes associated with oxidative damage prevention (UAS-hSOD1 and UAS-GCLc) or removal (EP-UAS-Atg8a and UAS-dTOR (FRB) ) failed to increase mean life spans in any expression pattern in ..
  12. Calap Quintana P, Soriano S, Llorens J, Al Ramahi I, Botas J, Moltó M, et al. TORC1 Inhibition by Rapamycin Promotes Antioxidant Defences in a Drosophila Model of Friedreich's Ataxia. PLoS ONE. 2015;10:e0132376 pubmed publisher
    ..These results point to the TORC1 pathway as a new potential therapeutic target for FRDA and as a guide to finding new promising molecules for disease treatment. ..
  13. Pandey A, Vimal D, Chandra S, Saini S, Narayan G, Kar Chowdhuri D. Long-term dietary exposure to low concentration of dichloroacetic acid promoted longevity and attenuated cellular and functional declines in aged Drosophila melanogaster. Age (Dordr). 2014;36:9628 pubmed publisher
    ..examined locomotor performance, ROS generation, glutathione (GSH) depletion, expression of GSH-synthesizing genes (gclc and gclm), and hsps at different days (0, 10, 20, 30, 40, 50) of the age in flies after prolonged DCA exposure...
  14. Toroser D, Yarian C, Orr W, Sohal R. Mechanisms of gamma-glutamylcysteine ligase regulation. Biochim Biophys Acta. 2006;1760:233-44 pubmed
    ..objective of this study was to investigate the mechanisms regulating the activity of gamma-glutamylcysteine ligase (GCL; EC, the rate limiting enzyme in glutathione biosynthesis...