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Gene Review

Ces1g  -  carboxylesterase 1G

Mus musculus

Synonyms: Acyl-coenzyme A:cholesterol acyltransferase, Carboxylesterase 1G, Ces-1, Ces1, ES-x, ...
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Disease relevance of Ces1

  • We demonstrate that each of these ONYX-015-based adenoviruses expresses an active CE enzyme that can efficiently convert CPT-11 to SN-38 [1].
  • However, in contrast to CPT-11, a water-soluble CPT analogue that was recently approved for second line treatment of colorectal cancer, the 20(S)-glycinate esters do not require carboxylesterase for conversion to their active forms [2].
  • Reversal of CPT-11 resistance of lung cancer cells by adenovirus-mediated gene transfer of the human carboxylesterase cDNA [3].
  • Cell toxicity induced by inhibition of acyl coenzyme A:cholesterol acyltransferase and accumulation of unesterified cholesterol [4].
  • Genetic analyses identified Ses1 as a significant quantitative trait locus influencing the carrier state of 129S6 mice following a sublethal challenge with Salmonella enterica serovar Enteritidis [5].

High impact information on Ces1

  • Finally, we demonstrate that we can achieve transgene expression and activity in vivo in a human tumor xenograft model, and that treatment with a CE-expressing virus in combination with CPT-11 enhances survival of tumor-bearing mice [1].
  • AdCMV.CE infection resulted in an increase in functional CE protein in resistant cells in vitro that was sufficient to convert CPT-11 to its active metabolite, SN-38, and effectively suppressed resistant cell growth in vitro in the presence of CPT-11 [3].
  • N-terminal amino acid sequence analysis indicated that the isolated enzyme was rat serum carboxylesterase [6].
  • Similarly, the nonacetylated derivative, N-(deoxyguanosin-8-yl) benzidine, was synthesized by carboxylesterase treatment of N-(deoxyguanosin-8-yl)-N'-acetylbenzidine and was shown not to occur in rat and mouse liver DNA [7].
  • Identification, expression, and purification of a pyrethroid-hydrolyzing carboxylesterase from mouse liver microsomes [8].

Chemical compound and disease context of Ces1


Biological context of Ces1


Anatomical context of Ces1

  • Mouse peritoneal macrophages (MPMs) or J774 macrophages were loaded with cholesteryl esters using acetylated LDL and FC/phospholipid dispersions and were subsequently exposed to an acyl coenzyme A:cholesterol acyltransferase (ACAT) inhibitor [17].
  • The model foam cells were then incubated for up to 5 days with an acyl-coenzyme A:cholesterol acyltransferase (ACAT) inhibitor (CP-113,818) in the absence of an extracellular FC acceptor to allow intracellular accumulation of FC [18].
  • To determine the chromosome location of the largest unmapped linkage group in the rat (LG V containing multiple carboxylesterase loci), we used single-strand conformation polymorphism analysis to identify the rat esterase-10 gene in a panel of rat x mouse somatic cell hybrids [16].
  • The loss in carboxylesterase activity correlated with decreased immunodetectable hydrolase A in microsomes incubated with VC, PMSF, or PMSF and VC [19].
  • All cell types of the respiratory epithelium had some carboxylesterase activity, with varying intensities between individual cell populations [20].

Associations of Ces1 with chemical compounds

  • We further demonstrate that feeding mice with diets containing cholestyramine or sodium cholate increases mRNA-expression of ES-x in liver 2.5- to 3-fold [13].
  • 9. Treatment with endoglycosidase H caused an increase in electrophoretic mobility indicating that the liver carboxylesterase was a glycoprotein of the high mannose type [21].
  • A second carboxylesterase gene (NCBI accession number NM_133960), isolated during a cDNA mouse liver library screening, was also found to hydrolyze pyrethroids [8].
  • Treating Y-1 cells with the acyl coenzyme A:cholesterol acyltransferase inhibitor, 58-035, caused cellular cholesteryl ester depletion and rendered more apparent the effect of dibutyryl-cAMP to cause cellular free cholesterol depletion [22].
  • Male mice were treated (i.p.) for 3 days with 15 different environmentally encountered epoxides, and the effects of these compounds on liver microsomal and cytosolic epoxide hydrolase (mEH and cEH), glutathione S-transferase (mGST and cGST) and carboxylesterase (mCE) activities were determined [23].

Enzymatic interactions of Ces1


Other interactions of Ces1


Analytical, diagnostic and therapeutic context of Ces1


  1. A prodrug strategy using ONYX-015-based replicating adenoviruses to deliver rabbit carboxylesterase to tumor cells for conversion of CPT-11 to SN-38. Stubdal, H., Perin, N., Lemmon, M., Holman, P., Bauzon, M., Potter, P.M., Danks, M.K., Fattaey, A., Dubensky, T., Johnson, L. Cancer Res. (2003) [Pubmed]
  2. Water soluble 20(S)-glycinate esters of 10,11-methylenedioxycamptothecins are highly active against human breast cancer xenografts. Wadkins, R.M., Potter, P.M., Vladu, B., Marty, J., Mangold, G., Weitman, S., Manikumar, G., Wani, M.C., Wall, M.E., Von Hoff, D.D. Cancer Res. (1999) [Pubmed]
  3. Reversal of CPT-11 resistance of lung cancer cells by adenovirus-mediated gene transfer of the human carboxylesterase cDNA. Kojima, A., Hackett, N.R., Crystal, R.G. Cancer Res. (1998) [Pubmed]
  4. Cell toxicity induced by inhibition of acyl coenzyme A:cholesterol acyltransferase and accumulation of unesterified cholesterol. Warner, G.J., Stoudt, G., Bamberger, M., Johnson, W.J., Rothblat, G.H. J. Biol. Chem. (1995) [Pubmed]
  5. Influence of Slc11a1 on the outcome of Salmonella enterica serovar Enteritidis infection in mice is associated with Th polarization. Caron, J., Larivière, L., Nacache, M., Tam, M., Stevenson, M.M., McKerly, C., Gros, P., Malo, D. Infect. Immun. (2006) [Pubmed]
  6. The role of rat serum carboxylesterase in the activation of paclitaxel and camptothecin prodrugs. Senter, P.D., Marquardt, H., Thomas, B.A., Hammock, B.D., Frank, I.S., Svensson, H.P. Cancer Res. (1996) [Pubmed]
  7. Covalent binding of benzidine and N-acetylbenzidine to DNA at the C-8 atom of deoxyguanosine in vivo and in vitro. Martin, C.N., Beland, F.A., Roth, R.W., Kadlubar, F.F. Cancer Res. (1982) [Pubmed]
  8. Identification, expression, and purification of a pyrethroid-hydrolyzing carboxylesterase from mouse liver microsomes. Stok, J.E., Huang, H., Jones, P.D., Wheelock, C.E., Morisseau, C., Hammock, B.D. J. Biol. Chem. (2004) [Pubmed]
  9. Metabolism of T-2 toxin by rat liver carboxylesterase. Johnsen, H., Odden, E., Lie, O., Johnsen, B.A., Fonnum, F. Biochem. Pharmacol. (1986) [Pubmed]
  10. Urethane-induced lung hyperplasia: carboxylesterase isozymes as markers in lung pathology. Böcking, A., Mittermayer, C., von Deimling, O. Lab. Invest. (1981) [Pubmed]
  11. The effects of differential induction of cytochrome P-450, carboxylesterase and glutathione S-transferase activities on malathion toxicity in mice. Ketterman, A.J., Pond, S.M., Becker, C.E. Toxicol. Appl. Pharmacol. (1987) [Pubmed]
  12. Unidirectional cross-tolerance between the carbamate insecticide propoxur and the organophosphate disulfoton in mice. Costa, L.G., Murphy, S.D. Fundamental and applied toxicology : official journal of the Society of Toxicology. (1983) [Pubmed]
  13. Cloning and sequencing of a novel murine liver carboxylesterase cDNA. Ellinghaus, P., Seedorf, U., Assmann, G. Biochim. Biophys. Acta (1998) [Pubmed]
  14. The use of transient chromatin immunoprecipitation assays to test models for E2F1-specific transcriptional activation. Lavrrar, J.L., Farnham, P.J. J. Biol. Chem. (2004) [Pubmed]
  15. Altered irinotecan and SN-38 disposition after intravenous and oral administration of irinotecan in mice bearing human neuroblastoma xenografts. Zamboni, W.C., Houghton, P.J., Thompson, J., Cheshire, P.J., Hanna, S.K., Richmond, L.B., Lou, X., Stewart, C.F. Clin. Cancer Res. (1998) [Pubmed]
  16. Assignment of rat linkage group V to chromosome 19 by single-strand conformation polymorphism analysis of somatic cell hybrids. Pravenec, M., Simonet, L., Kren, V., St Lezin, E., Levan, G., Szpirer, J., Szpirer, C., Kurtz, T. Genomics (1992) [Pubmed]
  17. Effects of intracellular free cholesterol accumulation on macrophage viability: a model for foam cell death. Kellner-Weibel, G., Jerome, W.G., Small, D.M., Warner, G.J., Stoltenborg, J.K., Kearney, M.A., Corjay, M.H., Phillips, M.C., Rothblat, G.H. Arterioscler. Thromb. Vasc. Biol. (1998) [Pubmed]
  18. Crystallization of free cholesterol in model macrophage foam cells. Kellner-Weibel, G., Yancey, P.G., Jerome, W.G., Walser, T., Mason, R.P., Phillips, M.C., Rothblat, G.H. Arterioscler. Thromb. Vasc. Biol. (1999) [Pubmed]
  19. Inactivation of cytochrome P-450 (CYP2E1) and carboxylesterase (hydrolase A) enzymes by vinyl carbamate in murine pulmonary microsomes. Lee, R.P., Forkert, P.G. Drug Metab. Dispos. (1999) [Pubmed]
  20. Biochemical quantitation and histochemical localization of carboxylesterase in the nasal passages of the Fischer-344 rat and B6C3F1 mouse. Bogdanffy, M.S., Randall, H.W., Morgan, K.T. Toxicol. Appl. Pharmacol. (1987) [Pubmed]
  21. Purification and cloning of a broad substrate specificity human liver carboxylesterase that catalyzes the hydrolysis of cocaine and heroin. Pindel, E.V., Kedishvili, N.Y., Abraham, T.L., Brzezinski, M.R., Zhang, J., Dean, R.A., Bosron, W.F. J. Biol. Chem. (1997) [Pubmed]
  22. Plasma membrane cholesterol is utilized as steroidogenic substrate in Y-1 mouse adrenal tumor cells and normal sheep adrenal cells. Gocze, P.M., Freeman, D.A. Exp. Cell Res. (1993) [Pubmed]
  23. Effects of environmentally encountered epoxides on mouse liver epoxide-metabolizing enzymes. Moody, D.E., Montgomery, K.A., Ashour, M.B., Hammock, B.D. Biochem. Pharmacol. (1991) [Pubmed]
  24. Metabolic inactivation of 2-oxiranylmethyl 2-ethyl-2,5-dimethylhexanoate (C10GE) in skin, lung and liver of human, rat and mouse. Boogaard, P.J., van Elburg, P.A., de Kloe, K.P., Watson, W.P., van Sittert, N.J. Xenobiotica (1999) [Pubmed]
  25. Phosphoacetylcholinesterase: toxicity of phosphorus oxychloride to mammals and insects that can be attributed to selective phosphorylation of acetylcholinesterase by phosphorodichloridic acid. Quistad, G.B., Zhang, N., Sparks, S.E., Casida, J.E. Chem. Res. Toxicol. (2000) [Pubmed]
  26. Esterase-30 (ES-30) of the house mouse: biochemical characterization and genetics of a new carboxylesterase isozyme linked to cluster-2 loci on chromosome 8. Ronai, A., Berning, W., Gaa, A., von Deimling, O. Biochem. Genet. (1993) [Pubmed]
  27. Esterase-23 (ES-23): characterization of a new carboxylesterase isozyme (EC of the house mouse, genetically linked to ES-2 on chromosome 8. von Deimling, O.H. Biochem. Genet. (1984) [Pubmed]
  28. Separation and quantitative recovery of mouse serum arylesterase and carboxylesterase activity. Connelly, P.W., Maguire, G.F., Draganov, D.I. J. Lipid Res. (2004) [Pubmed]
  29. Molecular cloning and identification of a rat serum carboxylesterase expressed in the liver. Alexson, S.E., Finlay, T.H., Hellman, U., Svensson, L.T., Diczfalusy, U., Eggertsen, G. J. Biol. Chem. (1994) [Pubmed]
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