Methionine deprivation induces growth arrest and death of cancer cells. To eliminate l-methionine we produced, purified, and characterized the recombinant pyridoxal 5'-phosphate (PLP)-dependent l-methionine γ-lyase (MGL)- BL929 from the cheese-ripening Brevibacterium aurantiacum Transformation of an Escherichia coli strain with the gene BL929 from B. aurantiacum optimized for E. coli expression led to production of the MGL-BL929. Elimination of l-methionine and cytotoxicity in vitro were assessed, and methylation-sensitive epigenetics was explored for changes resulting from exposure of cancer cells to the enzyme. A bioreactor was built by encapsulation of the protein in human erythrocytes to achieve sustained elimination of l-methionine in extracellular fluids. Catalysis was limited to α,γ-elimination of l-methionine and l-homocysteine. The enzyme had no activity on other sulfur-containing amino acids. Enzyme activity decreased in presence of serum albumin or plasma resulting from reduction of PLP availability. Elimination of l-methionine induced cytotoxicity on a vast panel of human cancer cell lines and spared normal cells. Exposure of colorectal carcinoma cells to the MGL-BL929 reduced methyl-CpG levels of hypermethylated gene promoters including that of CDKN2A, whose mRNA expression was increased, together with a decrease in global histone H3 dimethyl lysine 9. The MGL-erythrocyte bioreactor durably preserves enzyme activity in vitro and strongly eliminates l-methionine from medium.

Assistance Publique Hôpitaux de Paris Hospital Necker Enfants Malades Paris France

Assistance Publique Hôpitaux de Paris Hospital Paul Brousse Villejuif France

CNRS UMR 8601 Paris France

CRH Department of Protein Biochemistry and Proteomics Palacký University Olomouc Czech Republic

INRA AgroParisTech UMR 782 GMPA Thiverval Grignon France

INSERM U1193 Villejuif France

INSERM U1197 Villejuif France

INSERM U935 Villejuif France

Institut Jean Pierre Bourgin INRA AgroParisTech University Paris Saclay Versailles France

University of Urbino Carlo Bo Urbino Italy

University Paris Descartes Paris France

University Paris Saclay Paris France

University Paris Sud Villejuif France

YGM Consult SAS Paris France

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$a Machover, David $u Assistance Publique-Hôpitaux de Paris, Hospital Paul-Brousse, Villejuif, France (D.M., J.H., E.G., R.S.,); INSERM U935, Villejuif, France (D.M., C.D., F.H.-R., C.B.); University Paris-Sud, Villejuif, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University Paris-Saclay, Paris, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University of Urbino Carlo Bo, Urbino, Italy (L.R., F.P., M.M.); INSERM U1193, Villejuif, France (J.H., R.S.); INSERM U1197, Villejuif, France (R.M.); INRA-AgroParisTech, UMR 782 GMPA, Thiverval-Grignon, France (P.Bo.); Institut Jean-Pierre Bourgin, INRA-AgroParisTech, University Paris-Saclay, Versailles, France (P.Br.); CRH-Department of Protein Biochemistry and Proteomics, Palacký University, Olomouc, Czech Republic (D.K.); YGM Consult SAS, Paris, France (Y.G.-M.); CNRS UMR 8601, Paris, France (J.D.); Assistance Publique-Hôpitaux de Paris, Hospital Necker-Enfants Malades, Paris. France (B.C.-V.); and University Paris-Descartes, Paris, France (B.C.-V., J.D.) david.machover1@orange.fr david.machover@aphp.fr.

245    10

$a Effects in Cancer Cells of the Recombinant l-Methionine Gamma-Lyase from Brevibacterium aurantiacum. Encapsulation in Human Erythrocytes for Sustained l-Methionine Elimination / $c D. Machover, L. Rossi, J. Hamelin, C. Desterke, E. Goldschmidt, B. Chadefaux-Vekemans, P. Bonnarme, P. Briozzo, D. Kopečný, F. Pierigè, M. Magnani, R. Mollicone, F. Haghighi-Rad, Y. Gaston-Mathé, J. Dairou, C. Boucheix, R. Saffroy,

520    9_

$a Methionine deprivation induces growth arrest and death of cancer cells. To eliminate l-methionine we produced, purified, and characterized the recombinant pyridoxal 5'-phosphate (PLP)-dependent l-methionine γ-lyase (MGL)- BL929 from the cheese-ripening Brevibacterium aurantiacum Transformation of an Escherichia coli strain with the gene BL929 from B. aurantiacum optimized for E. coli expression led to production of the MGL-BL929. Elimination of l-methionine and cytotoxicity in vitro were assessed, and methylation-sensitive epigenetics was explored for changes resulting from exposure of cancer cells to the enzyme. A bioreactor was built by encapsulation of the protein in human erythrocytes to achieve sustained elimination of l-methionine in extracellular fluids. Catalysis was limited to α,γ-elimination of l-methionine and l-homocysteine. The enzyme had no activity on other sulfur-containing amino acids. Enzyme activity decreased in presence of serum albumin or plasma resulting from reduction of PLP availability. Elimination of l-methionine induced cytotoxicity on a vast panel of human cancer cell lines and spared normal cells. Exposure of colorectal carcinoma cells to the MGL-BL929 reduced methyl-CpG levels of hypermethylated gene promoters including that of CDKN2A, whose mRNA expression was increased, together with a decrease in global histone H3 dimethyl lysine 9. The MGL-erythrocyte bioreactor durably preserves enzyme activity in vitro and strongly eliminates l-methionine from medium.

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655    _2

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700    1_

$a Rossi, Luigia $u Assistance Publique-Hôpitaux de Paris, Hospital Paul-Brousse, Villejuif, France (D.M., J.H., E.G., R.S.,); INSERM U935, Villejuif, France (D.M., C.D., F.H.-R., C.B.); University Paris-Sud, Villejuif, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University Paris-Saclay, Paris, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University of Urbino Carlo Bo, Urbino, Italy (L.R., F.P., M.M.); INSERM U1193, Villejuif, France (J.H., R.S.); INSERM U1197, Villejuif, France (R.M.); INRA-AgroParisTech, UMR 782 GMPA, Thiverval-Grignon, France (P.Bo.); Institut Jean-Pierre Bourgin, INRA-AgroParisTech, University Paris-Saclay, Versailles, France (P.Br.); CRH-Department of Protein Biochemistry and Proteomics, Palacký University, Olomouc, Czech Republic (D.K.); YGM Consult SAS, Paris, France (Y.G.-M.); CNRS UMR 8601, Paris, France (J.D.); Assistance Publique-Hôpitaux de Paris, Hospital Necker-Enfants Malades, Paris. France (B.C.-V.); and University Paris-Descartes, Paris, France (B.C.-V., J.D.).

700    1_

$a Hamelin, Jocelyne $u Assistance Publique-Hôpitaux de Paris, Hospital Paul-Brousse, Villejuif, France (D.M., J.H., E.G., R.S.,); INSERM U935, Villejuif, France (D.M., C.D., F.H.-R., C.B.); University Paris-Sud, Villejuif, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University Paris-Saclay, Paris, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University of Urbino Carlo Bo, Urbino, Italy (L.R., F.P., M.M.); INSERM U1193, Villejuif, France (J.H., R.S.); INSERM U1197, Villejuif, France (R.M.); INRA-AgroParisTech, UMR 782 GMPA, Thiverval-Grignon, France (P.Bo.); Institut Jean-Pierre Bourgin, INRA-AgroParisTech, University Paris-Saclay, Versailles, France (P.Br.); CRH-Department of Protein Biochemistry and Proteomics, Palacký University, Olomouc, Czech Republic (D.K.); YGM Consult SAS, Paris, France (Y.G.-M.); CNRS UMR 8601, Paris, France (J.D.); Assistance Publique-Hôpitaux de Paris, Hospital Necker-Enfants Malades, Paris. France (B.C.-V.); and University Paris-Descartes, Paris, France (B.C.-V., J.D.).

700    1_

$a Desterke, Christophe $u Assistance Publique-Hôpitaux de Paris, Hospital Paul-Brousse, Villejuif, France (D.M., J.H., E.G., R.S.,); INSERM U935, Villejuif, France (D.M., C.D., F.H.-R., C.B.); University Paris-Sud, Villejuif, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University Paris-Saclay, Paris, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University of Urbino Carlo Bo, Urbino, Italy (L.R., F.P., M.M.); INSERM U1193, Villejuif, France (J.H., R.S.); INSERM U1197, Villejuif, France (R.M.); INRA-AgroParisTech, UMR 782 GMPA, Thiverval-Grignon, France (P.Bo.); Institut Jean-Pierre Bourgin, INRA-AgroParisTech, University Paris-Saclay, Versailles, France (P.Br.); CRH-Department of Protein Biochemistry and Proteomics, Palacký University, Olomouc, Czech Republic (D.K.); YGM Consult SAS, Paris, France (Y.G.-M.); CNRS UMR 8601, Paris, France (J.D.); Assistance Publique-Hôpitaux de Paris, Hospital Necker-Enfants Malades, Paris. France (B.C.-V.); and University Paris-Descartes, Paris, France (B.C.-V., J.D.).

700    1_

$a Goldschmidt, Emma $u Assistance Publique-Hôpitaux de Paris, Hospital Paul-Brousse, Villejuif, France (D.M., J.H., E.G., R.S.,); INSERM U935, Villejuif, France (D.M., C.D., F.H.-R., C.B.); University Paris-Sud, Villejuif, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University Paris-Saclay, Paris, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University of Urbino Carlo Bo, Urbino, Italy (L.R., F.P., M.M.); INSERM U1193, Villejuif, France (J.H., R.S.); INSERM U1197, Villejuif, France (R.M.); INRA-AgroParisTech, UMR 782 GMPA, Thiverval-Grignon, France (P.Bo.); Institut Jean-Pierre Bourgin, INRA-AgroParisTech, University Paris-Saclay, Versailles, France (P.Br.); CRH-Department of Protein Biochemistry and Proteomics, Palacký University, Olomouc, Czech Republic (D.K.); YGM Consult SAS, Paris, France (Y.G.-M.); CNRS UMR 8601, Paris, France (J.D.); Assistance Publique-Hôpitaux de Paris, Hospital Necker-Enfants Malades, Paris. France (B.C.-V.); and University Paris-Descartes, Paris, France (B.C.-V., J.D.).

700    1_

$a Chadefaux-Vekemans, Bernadette $u Assistance Publique-Hôpitaux de Paris, Hospital Paul-Brousse, Villejuif, France (D.M., J.H., E.G., R.S.,); INSERM U935, Villejuif, France (D.M., C.D., F.H.-R., C.B.); University Paris-Sud, Villejuif, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University Paris-Saclay, Paris, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University of Urbino Carlo Bo, Urbino, Italy (L.R., F.P., M.M.); INSERM U1193, Villejuif, France (J.H., R.S.); INSERM U1197, Villejuif, France (R.M.); INRA-AgroParisTech, UMR 782 GMPA, Thiverval-Grignon, France (P.Bo.); Institut Jean-Pierre Bourgin, INRA-AgroParisTech, University Paris-Saclay, Versailles, France (P.Br.); CRH-Department of Protein Biochemistry and Proteomics, Palacký University, Olomouc, Czech Republic (D.K.); YGM Consult SAS, Paris, France (Y.G.-M.); CNRS UMR 8601, Paris, France (J.D.); Assistance Publique-Hôpitaux de Paris, Hospital Necker-Enfants Malades, Paris. France (B.C.-V.); and University Paris-Descartes, Paris, France (B.C.-V., J.D.).

700    1_

$a Bonnarme, Pascal $u Assistance Publique-Hôpitaux de Paris, Hospital Paul-Brousse, Villejuif, France (D.M., J.H., E.G., R.S.,); INSERM U935, Villejuif, France (D.M., C.D., F.H.-R., C.B.); University Paris-Sud, Villejuif, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University Paris-Saclay, Paris, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University of Urbino Carlo Bo, Urbino, Italy (L.R., F.P., M.M.); INSERM U1193, Villejuif, France (J.H., R.S.); INSERM U1197, Villejuif, France (R.M.); INRA-AgroParisTech, UMR 782 GMPA, Thiverval-Grignon, France (P.Bo.); Institut Jean-Pierre Bourgin, INRA-AgroParisTech, University Paris-Saclay, Versailles, France (P.Br.); CRH-Department of Protein Biochemistry and Proteomics, Palacký University, Olomouc, Czech Republic (D.K.); YGM Consult SAS, Paris, France (Y.G.-M.); CNRS UMR 8601, Paris, France (J.D.); Assistance Publique-Hôpitaux de Paris, Hospital Necker-Enfants Malades, Paris. France (B.C.-V.); and University Paris-Descartes, Paris, France (B.C.-V., J.D.).

700    1_

$a Briozzo, Pierre $u Assistance Publique-Hôpitaux de Paris, Hospital Paul-Brousse, Villejuif, France (D.M., J.H., E.G., R.S.,); INSERM U935, Villejuif, France (D.M., C.D., F.H.-R., C.B.); University Paris-Sud, Villejuif, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University Paris-Saclay, Paris, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University of Urbino Carlo Bo, Urbino, Italy (L.R., F.P., M.M.); INSERM U1193, Villejuif, France (J.H., R.S.); INSERM U1197, Villejuif, France (R.M.); INRA-AgroParisTech, UMR 782 GMPA, Thiverval-Grignon, France (P.Bo.); Institut Jean-Pierre Bourgin, INRA-AgroParisTech, University Paris-Saclay, Versailles, France (P.Br.); CRH-Department of Protein Biochemistry and Proteomics, Palacký University, Olomouc, Czech Republic (D.K.); YGM Consult SAS, Paris, France (Y.G.-M.); CNRS UMR 8601, Paris, France (J.D.); Assistance Publique-Hôpitaux de Paris, Hospital Necker-Enfants Malades, Paris. France (B.C.-V.); and University Paris-Descartes, Paris, France (B.C.-V., J.D.).

700    1_

$a Kopečný, David $u Assistance Publique-Hôpitaux de Paris, Hospital Paul-Brousse, Villejuif, France (D.M., J.H., E.G., R.S.,); INSERM U935, Villejuif, France (D.M., C.D., F.H.-R., C.B.); University Paris-Sud, Villejuif, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University Paris-Saclay, Paris, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University of Urbino Carlo Bo, Urbino, Italy (L.R., F.P., M.M.); INSERM U1193, Villejuif, France (J.H., R.S.); INSERM U1197, Villejuif, France (R.M.); INRA-AgroParisTech, UMR 782 GMPA, Thiverval-Grignon, France (P.Bo.); Institut Jean-Pierre Bourgin, INRA-AgroParisTech, University Paris-Saclay, Versailles, France (P.Br.); CRH-Department of Protein Biochemistry and Proteomics, Palacký University, Olomouc, Czech Republic (D.K.); YGM Consult SAS, Paris, France (Y.G.-M.); CNRS UMR 8601, Paris, France (J.D.); Assistance Publique-Hôpitaux de Paris, Hospital Necker-Enfants Malades, Paris. France (B.C.-V.); and University Paris-Descartes, Paris, France (B.C.-V., J.D.).

700    1_

$a Pierigè, Francesca $u Assistance Publique-Hôpitaux de Paris, Hospital Paul-Brousse, Villejuif, France (D.M., J.H., E.G., R.S.,); INSERM U935, Villejuif, France (D.M., C.D., F.H.-R., C.B.); University Paris-Sud, Villejuif, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University Paris-Saclay, Paris, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University of Urbino Carlo Bo, Urbino, Italy (L.R., F.P., M.M.); INSERM U1193, Villejuif, France (J.H., R.S.); INSERM U1197, Villejuif, France (R.M.); INRA-AgroParisTech, UMR 782 GMPA, Thiverval-Grignon, France (P.Bo.); Institut Jean-Pierre Bourgin, INRA-AgroParisTech, University Paris-Saclay, Versailles, France (P.Br.); CRH-Department of Protein Biochemistry and Proteomics, Palacký University, Olomouc, Czech Republic (D.K.); YGM Consult SAS, Paris, France (Y.G.-M.); CNRS UMR 8601, Paris, France (J.D.); Assistance Publique-Hôpitaux de Paris, Hospital Necker-Enfants Malades, Paris. France (B.C.-V.); and University Paris-Descartes, Paris, France (B.C.-V., J.D.).

700    1_

$a Magnani, Mauro $u Assistance Publique-Hôpitaux de Paris, Hospital Paul-Brousse, Villejuif, France (D.M., J.H., E.G., R.S.,); INSERM U935, Villejuif, France (D.M., C.D., F.H.-R., C.B.); University Paris-Sud, Villejuif, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University Paris-Saclay, Paris, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University of Urbino Carlo Bo, Urbino, Italy (L.R., F.P., M.M.); INSERM U1193, Villejuif, France (J.H., R.S.); INSERM U1197, Villejuif, France (R.M.); INRA-AgroParisTech, UMR 782 GMPA, Thiverval-Grignon, France (P.Bo.); Institut Jean-Pierre Bourgin, INRA-AgroParisTech, University Paris-Saclay, Versailles, France (P.Br.); CRH-Department of Protein Biochemistry and Proteomics, Palacký University, Olomouc, Czech Republic (D.K.); YGM Consult SAS, Paris, France (Y.G.-M.); CNRS UMR 8601, Paris, France (J.D.); Assistance Publique-Hôpitaux de Paris, Hospital Necker-Enfants Malades, Paris. France (B.C.-V.); and University Paris-Descartes, Paris, France (B.C.-V., J.D.).

700    1_

$a Mollicone, Rosella $u Assistance Publique-Hôpitaux de Paris, Hospital Paul-Brousse, Villejuif, France (D.M., J.H., E.G., R.S.,); INSERM U935, Villejuif, France (D.M., C.D., F.H.-R., C.B.); University Paris-Sud, Villejuif, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University Paris-Saclay, Paris, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University of Urbino Carlo Bo, Urbino, Italy (L.R., F.P., M.M.); INSERM U1193, Villejuif, France (J.H., R.S.); INSERM U1197, Villejuif, France (R.M.); INRA-AgroParisTech, UMR 782 GMPA, Thiverval-Grignon, France (P.Bo.); Institut Jean-Pierre Bourgin, INRA-AgroParisTech, University Paris-Saclay, Versailles, France (P.Br.); CRH-Department of Protein Biochemistry and Proteomics, Palacký University, Olomouc, Czech Republic (D.K.); YGM Consult SAS, Paris, France (Y.G.-M.); CNRS UMR 8601, Paris, France (J.D.); Assistance Publique-Hôpitaux de Paris, Hospital Necker-Enfants Malades, Paris. France (B.C.-V.); and University Paris-Descartes, Paris, France (B.C.-V., J.D.).

700    1_

$a Haghighi-Rad, Farhad $u Assistance Publique-Hôpitaux de Paris, Hospital Paul-Brousse, Villejuif, France (D.M., J.H., E.G., R.S.,); INSERM U935, Villejuif, France (D.M., C.D., F.H.-R., C.B.); University Paris-Sud, Villejuif, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University Paris-Saclay, Paris, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University of Urbino Carlo Bo, Urbino, Italy (L.R., F.P., M.M.); INSERM U1193, Villejuif, France (J.H., R.S.); INSERM U1197, Villejuif, France (R.M.); INRA-AgroParisTech, UMR 782 GMPA, Thiverval-Grignon, France (P.Bo.); Institut Jean-Pierre Bourgin, INRA-AgroParisTech, University Paris-Saclay, Versailles, France (P.Br.); CRH-Department of Protein Biochemistry and Proteomics, Palacký University, Olomouc, Czech Republic (D.K.); YGM Consult SAS, Paris, France (Y.G.-M.); CNRS UMR 8601, Paris, France (J.D.); Assistance Publique-Hôpitaux de Paris, Hospital Necker-Enfants Malades, Paris. France (B.C.-V.); and University Paris-Descartes, Paris, France (B.C.-V., J.D.).

700    1_

$a Gaston-Mathé, Yann $u Assistance Publique-Hôpitaux de Paris, Hospital Paul-Brousse, Villejuif, France (D.M., J.H., E.G., R.S.,); INSERM U935, Villejuif, France (D.M., C.D., F.H.-R., C.B.); University Paris-Sud, Villejuif, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University Paris-Saclay, Paris, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University of Urbino Carlo Bo, Urbino, Italy (L.R., F.P., M.M.); INSERM U1193, Villejuif, France (J.H., R.S.); INSERM U1197, Villejuif, France (R.M.); INRA-AgroParisTech, UMR 782 GMPA, Thiverval-Grignon, France (P.Bo.); Institut Jean-Pierre Bourgin, INRA-AgroParisTech, University Paris-Saclay, Versailles, France (P.Br.); CRH-Department of Protein Biochemistry and Proteomics, Palacký University, Olomouc, Czech Republic (D.K.); YGM Consult SAS, Paris, France (Y.G.-M.); CNRS UMR 8601, Paris, France (J.D.); Assistance Publique-Hôpitaux de Paris, Hospital Necker-Enfants Malades, Paris. France (B.C.-V.); and University Paris-Descartes, Paris, France (B.C.-V., J.D.).

700    1_

$a Dairou, Julien $u Assistance Publique-Hôpitaux de Paris, Hospital Paul-Brousse, Villejuif, France (D.M., J.H., E.G., R.S.,); INSERM U935, Villejuif, France (D.M., C.D., F.H.-R., C.B.); University Paris-Sud, Villejuif, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University Paris-Saclay, Paris, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University of Urbino Carlo Bo, Urbino, Italy (L.R., F.P., M.M.); INSERM U1193, Villejuif, France (J.H., R.S.); INSERM U1197, Villejuif, France (R.M.); INRA-AgroParisTech, UMR 782 GMPA, Thiverval-Grignon, France (P.Bo.); Institut Jean-Pierre Bourgin, INRA-AgroParisTech, University Paris-Saclay, Versailles, France (P.Br.); CRH-Department of Protein Biochemistry and Proteomics, Palacký University, Olomouc, Czech Republic (D.K.); YGM Consult SAS, Paris, France (Y.G.-M.); CNRS UMR 8601, Paris, France (J.D.); Assistance Publique-Hôpitaux de Paris, Hospital Necker-Enfants Malades, Paris. France (B.C.-V.); and University Paris-Descartes, Paris, France (B.C.-V., J.D.).

700    1_

$a Boucheix, Claude $u Assistance Publique-Hôpitaux de Paris, Hospital Paul-Brousse, Villejuif, France (D.M., J.H., E.G., R.S.,); INSERM U935, Villejuif, France (D.M., C.D., F.H.-R., C.B.); University Paris-Sud, Villejuif, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University Paris-Saclay, Paris, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University of Urbino Carlo Bo, Urbino, Italy (L.R., F.P., M.M.); INSERM U1193, Villejuif, France (J.H., R.S.); INSERM U1197, Villejuif, France (R.M.); INRA-AgroParisTech, UMR 782 GMPA, Thiverval-Grignon, France (P.Bo.); Institut Jean-Pierre Bourgin, INRA-AgroParisTech, University Paris-Saclay, Versailles, France (P.Br.); CRH-Department of Protein Biochemistry and Proteomics, Palacký University, Olomouc, Czech Republic (D.K.); YGM Consult SAS, Paris, France (Y.G.-M.); CNRS UMR 8601, Paris, France (J.D.); Assistance Publique-Hôpitaux de Paris, Hospital Necker-Enfants Malades, Paris. France (B.C.-V.); and University Paris-Descartes, Paris, France (B.C.-V., J.D.).

700    1_

$a Saffroy, Raphaël $u Assistance Publique-Hôpitaux de Paris, Hospital Paul-Brousse, Villejuif, France (D.M., J.H., E.G., R.S.,); INSERM U935, Villejuif, France (D.M., C.D., F.H.-R., C.B.); University Paris-Sud, Villejuif, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University Paris-Saclay, Paris, France (D.M., J.H., C.D., R.M., F.H.-R., C.B., R.S.); University of Urbino Carlo Bo, Urbino, Italy (L.R., F.P., M.M.); INSERM U1193, Villejuif, France (J.H., R.S.); INSERM U1197, Villejuif, France (R.M.); INRA-AgroParisTech, UMR 782 GMPA, Thiverval-Grignon, France (P.Bo.); Institut Jean-Pierre Bourgin, INRA-AgroParisTech, University Paris-Saclay, Versailles, France (P.Br.); CRH-Department of Protein Biochemistry and Proteomics, Palacký University, Olomouc, Czech Republic (D.K.); YGM Consult SAS, Paris, France (Y.G.-M.); CNRS UMR 8601, Paris, France (J.D.); Assistance Publique-Hôpitaux de Paris, Hospital Necker-Enfants Malades, Paris. France (B.C.-V.); and University Paris-Descartes, Paris, France (B.C.-V., J.D.).

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$w MED00002900 $t The Journal of pharmacology and experimental therapeutics $x 1521-0103 $g Roč. 369, č. 3 (2019), s. 489-502

856    41

$u https://pubmed.ncbi.nlm.nih.gov/30940696 $y Pubmed

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