ГОСТРИЙ ДЕФІЦИТ ГЛУТАМІНУ ЗМІНЮЄ ЕКСПРЕСІЮ ГЕНІВ ПЕНТОЗО-ФОСФАТНОГО ШЛЯХУ У КЛІТИНАХ ГЛІОМИ ЛІНІЇ U87: ЕФЕКТ ВИКЛЮЧЕННЯ ERN1
Анотація
Пентозо-фосфатний цикл метаболізму глюкози відіграє важливу роль у рості злоякісних пухлин. Нами проведено вивчення експресії мРНК основних ензимів цього циклу (G6PD, TKT, TALDO1, PGLS та RPIA) а також глюкозо-6-фосфатізомерази (GPI) у клітинах гліоми лінії U87 з пригніченою функцією ERN1 (сигналювання від ендоплазматичного ретикулуму до ядра-1), основного сенсорно-сигнального ензиму стресу ендоплазматичного ретикулуму, в залежності від рівня глутаміну у середовищі вирощування клітин. Встановлено, що за умов пригнічення функції сигнального ензиму ERN1 рівень експресії генів TALDO1 та PGLS у клітинах гліоми істотно знижувався, а гена GPI збільшувався. В той же час, рівень експресії генів інших ензимів пентозо-фосфатного циклу при цьому істотно не змінювався. Також показано, що рівень експресії генів G6PD та GPI підвищується і знижується, відповідно, у клітинах гліоми за умов дефіциту глутаміну, а генів інших ензимів пентозо-фосфатного циклу при цьому істотно не змінювався. Більше того, виявлені зміни в експресії досліджених генів за умов дефіциту глутаміну залежали від функції сигнального ензиму ERN1. Таким чином, результати даної роботи вказують на те, що у клітинах гліоми лінії U87 за умов пригнічення функції сигнального ензиму ERN1 змінюється рівень експресії лише трьох досліджених генів і що за умов дефіциту глутаміну у середовищі вирощування клітин гліоми по-різному змінюється рівень експресії більшості досліджених генів, але ці зміни виявлялися переважно у клітинах за умов виключення ERN1.
Ключові слова: експресія генів, блокада ERN1, G6PD, TKT, TALDO1, PGLS, RPIA, GPI, дефіцит глутаміну, клітини гліоми лінії U87.
Посилання
Acosta-Alvear D., Zhou Y., Blais A., Tsikitis M., Lents N.H., Arias C., Lennon C.J., Kluger Y., Dynlacht D.D. XBP1 controls diverse cell type- and condition-specific transcriptional regulatory networks. Molecular Cell. 2007; 27: 53–66.
Aragón T., van Anken E., Pincus D., Serafimova I.M., Korennykh A.V., Rubio C.A., Walter P. Messenger RNA targeting to endoplasmic reticulum stress signalling sites.Nature. 2009; 457(7230): 736–740.
Auf G., Jabouille A., Delugin M., Guérit S., Pineau R., North S., Platonova N., Maitre M., Favereaux A., Seno M., Bikfalvi A., Minchenko D., Minchenko O., Moenner M. High epiregulin expression in human U87 glioma cells relies on IRE1 and promotes autocrine growth through EGF receptor.. BMC Cancer. 2013; 13(1): 597.
Auf G., Jabouille A., Guérit S., Pineau R., Delugin M., Bouchecareilh M., Favereaux A., Maitre M., Gaiser T., von Deimling A., Czabanka M., Vajkoczy P., Chevet E., Bikfalvi A., Moenner M. A shift from an angiogenic to invasive phenotype induced in malignant glioma by inhibition of the unfolded protein response sensor IRE1.. Proc. Natl. Acad. Sci. U.S.A. 2010; 107(35): 1555–15558.
Bakalets T., Minchenko D., Danilovskyi S., Minchenko O. Expression of protein kinase PLK family genes in U87 glioma cell line with suppressed function of ERN1 signaling enzyme of endoplasmic reticulum stress.. Visnyk Taras Shevchenko Kyiv National University. Biology. 2013; 63: 7–13.
Basu R., Barosa C., Basu A, Pattan V, Saad A, Jones J, Rizza R. Transaldolase exchange and its effects on measurements of gluconeogenesis in humans.. Am. J. Physiol. Endocrinol. Metab. 2011; 300(2): E296-E303.
Berry G.T. The unexplored potential of the pentose phosphate pathway in health and disease.. J. Inherit. Metab. Dis. 2008; 31(6): 661.
Bi M., Naczki C., Koritzinsky M., Fels D., Blais J., Hu N., Harding H., Novoa I., Varia M., Raleigh J., Scheuner D., Kaufman R.J., Bell J., Ron D., Wouters B.G., Koumenis C. ER stress-regulated translation increases tolerance to extreme hypoxia and promotes tumor growth.. EMBO J. 2005; 24(19): 3470–34815.
Drogat B., Auguste P., Nguyen D.T., Bouchecareilh M., Pineau R., Nalbantoglu J., Kaufman R.J., Chevet E., Bikfalvi A., Moenner M. IRE1 signaling is essential for ischemia-induced vascular endothelial growth factor-A expression and contributes to angiogenesis and tumor growth in vivo.. Cancer Res. 2007; 67: 6700–6707.
Du W., Jiang P., Mancuso A., Stonestrom A., Brewer M.D., Minn A.J., Mak T.W., Wu M., Yang X. TAp73 enhances the pentose phosphate pathway and supports cell proliferation.. Nat. Cell Biol. 2013; 15(8): 991–1000.
Fairbank M., St-Pierre P., Nabi I.R. The complex biology of autocrine motility factor/phosphoglucose isomerase (AMF/PGI) and its receptor, the gp78/AMFR E3 ubiquitin ligase. Mol. Biosyst. 2009; 5(8): 793–801.
Fels D.R., Koumenis C. The PERK/eIF2a/ATF4 module of the UPR in hypoxia resistance and tumor growth.. Cancer Biology & Therapy. 2006; 5(7): 723–728.
Fu M., Li L., Albrecht T., Johnson J.D., Kojic L.D., Nabi I.R. Autocrine motility factor phosphoglucose isomerase regulates ER stress and cell death through control of ER calcium release.. Cell Death Differ. 2011; 18(6): 1057–1070.
Funasaka T., Hogan V., Raz A. Phosphoglucose isomerase/autocrine motility factor mediates epithelial and mesenchymal phenotype conversions in breast cancer.. Cancer Res. 2009; 69(13): 5349–5356.
Garmash I.,Kompaniets D., Hubenia O., Minchenko D. Effect of hypoxia and glucose or glutamine deprivation on the expression of enolase and aldolase genes in glioma U87 cell line with suppressed function of ERN1 signaling enzyme.. Visnyk Taras Shevchenko Kyiv National Univ. Problems of the Regulation of Physiological Functions. 2013; 16: 5–9.
Hetz C., Chevet E., Harding H.P. Targeting the unfolded protein response in disease.. Nat. Rev. Drug Discov. 2013; 12(9): 703–719.
Hollien J., Lin J.H., Li H., Stevens N., Walter P., Weissman J. S. Regulated Ire1-dependent decay of messenger RNAs in mammalian cells.. J. Cell. Biol. 2009; 186(3): 323–331.
Hu T., Zhang C., Tang Q., Su Y., Li B., Chen L., Zhang Z., Cai T., Zhu Y. Variant G6PD levels promote tumor cell proliferation or apoptosis via the STAT3/5 pathway in the human melanoma xenograft mouse model. BMC Cancer. 2013; 13: 251р.
Kho D.H., Nangia-Makker P., Balan V., Hogan V., Tait L., Wang Y., Raz A. Autocrine motility factor promotes HER2 cleavage and signaling in breast cancer cells.. Cancer Res. 2013; 73(4): 1411–1419.
Jiang P., Du W., Yang X. A critical role of glucose-6-phosphate dehydrogenase in TAp73-mediated cell proliferation.. Cell Cycle. 2013; 12(24): 3720–3726.
Korennykh A.V., Egea P.F., Korostelev A.A., Finer-Moore J., Zhang C., Shokat K.M., Stroud R.M., Walter P. The unfolded protein response signals through high-order assembly of Ire1.. Nature. 2009; 457(7230): 687–693.
Lee J., Sun C., Zhou Y., Lee J., Gokalp D., Herrema H., Park S.W., Davis R.J., Ozcan U. p38 MAPK-mediated regulation of Xbp1s is crucial for glucose homeostasis.. Nature Medicine. 2011; 17(10): 1251–1260.
Minchenko D.O., Garmash I.A., Bashta Y.M., Kustkova G.S., Zalesna Y.D., Bikfalvi A., Minchenko O.H. ERN1 dependent expression of phosphoribosyl pyrophosphate synthetase genes in U87 glioma cells: effect of glucose or glutamine deprivation.. Int. J. Genomic Med. 2013; 1(1): 104(1–5).
Minchenko D., Hubenya O., Terletsky B., Kuznetsova A., Moenner M., Minchenko O. Blockade of the endoplasmic reticulum stress sensor inositol requiring enzyme-1 changes the expression of cyclin and growth arrest-specific genes in glioma cells.. Annales Universitatis Mariae Curie-Sklodowska. 2010; 23(3): 179–184.
Minchenko D.O., Karbovskyi L.L., Danilovskyi S.V., Kharkova A.P., Minchenko O.H. Expression of casein kinase genes in glioma cell line U87: effect of hypoxia and glucose or glutamine deprivation.. Nat. Sci. 2012a; 4(1): 38–46.
Minchenko D.O., Karbovskyi L.L., Danilovskyi S.V., Moenner M., Minchenko O.H. Effect of hypoxia and glutamine or glucose deprivation on the expression of retinoblastoma and retinoblastoma-related genes in ERN1 knockdown glioma U87 cell line.. Am. J. Mol. Biol. 2012b; 2(1): 21–31.
Minchenko O.H., Kubaichuk K.I., Minchenko D.O., Kovalevska O.V., Kulinich A.O., Lypova N.M. Molecular mechanisms of ERN1-mediated angiogenesis. Int. J. Physiol. Pathophysiol. 2014; 5(1): 1–22.
Minchenko D.О., Kubajchuk К.І., Ratushna O.O., Komisarenko S.V., Minchenko O.H. The effect of hypoxia and ischemic condition on the expression of VEGF genes in glioma U87 cells is dependent from ERN1 knockdown.. Adv. Biol. Chem. 2012c; 2(2): 198–206.
Moenner M., Pluquet O., Bouchecareilh M., Chevet E. Integrated endoplasmic reticulum stress responses in cancer.. Cancer Res. 2007; 67(22): 10631–10634.
Niinaka Y., Harada K., Fujimuro M., Oda M., Haga A., Hosoki M., Uzawa N., Arai N., Yamaguchi S., Yamashiro M., Raz A. Silencing of autocrine motility factor induces mesenchymal-to-epithelial transition and suppression of osteosarcoma pulmonary metastasis. Cancer Res. 2010; 70(22): 9483-9493.
Pan S., World C.J., Kovacs C.J., Berk B.C. Glucose 6-phosphate dehydrogenase is regulated through c-Src-mediated tyrosine phosphorylation in endothelial cells.. Arterioscler. Thromb. Vasc. Biol. 2009; 29(6): 895–901.
Pluquet O., Dejeans N., Bouchecareilh M., Lhomond S., Pineau R., Higa A., Delugin M., Combe C., Loriot S., Cubel G., Dugot-Senant N., Vital A., Loiseau H., Gosline S.J., Taouji S., Hallett M., Sarkaria J.N., Anderson K., Wu W., Rodriguez F.J., Rosenbaum J., Saltel F., Fernandez-Zapico M.E., Chevet E. Posttranscriptional regulation of PER1 underlies the oncogenic function of IREα.. Cancer Res. 2013; 73(15): 4732–4743.
Qian Y., Banerjee S., Grossman C.E., Amidon W., Nagy G., Barcza M., Niland B., Karp D.R., Middleton F.A., Banki K., Perl A. Transaldolase deficiency influences the pentose phosphate pathway, mitochondrial homoeostasis and apoptosis signal processing.. Biochem. J. 2008; 415(1): 123-134.
Romero-Ramirez L., Cao H., Nelson D., Hammond E., Lee A.H., Yoshida H., Mori K., Glimcher L.H., Denko N.C., Giaccia A.J., Le Q.-T., Koong A.C. XBP1 is essential for survival under hypoxic conditions and is required for tumor growth.. Cancer Res. 2004; 64(17): 5943–5947.
Samland A.K., Sprenger G.A. Transaldolase: from biochemistry to human disease.. Int. J. Biochem. Cell. Biol. 2009; 41(7): 1482–1494.
Shelton P., Jaiswal A.K. The transcription factor NF-E2-related factor 2 (Nrf2): a protooncogene FASEB J. 2013; 27(2): 414-423.
Stanton R.C. Glucose-6-phosphate dehydrogenase, NADPH, and cell survival. IUBMB Life. 2012; 64(5): 362–369.
Tsutsumi S., Fukasawa T., Yamauchi H., Kato T., Kigure W., Morita H., Asao T., Kuwano H. Phosphoglucose isomerase enhances colorectal cancer metastasis.. Int. J. Oncol. 2009; 35(5): 1117–1121.
Wamelink M.M., Struys E.A., Jakobs C. The biochemistry, metabolism and inherited defects of the pentose phosphate pathway: a review.. J. Inherit. Metab. Dis. 2008; 31(6): 703–717.
Zhang K., Kaufman R.J. The unfolded protein response: a stress signaling pathway critical for health and disease.. Neurology. 2006; 66(2) (Suppl 1): 102–109.
Zhou Y., Lee J., Reno C.M., Sun C., Park S.W., Chung J., Lee J., Fisher S.J., White M.F., Biddinger S.B., Ozcan U. Regulation of glucose homeostasis through a XBP-1-FoxO1 interaction.. Nature Medicine. 2011; 17(3): 356–365.
Aragón T., van Anken E., Pincus D., Serafimova I.M., Korennykh A.V., Rubio C.A., Walter P. Messenger RNA targeting to endoplasmic reticulum stress signalling sites.Nature. 2009; 457(7230): 736–740.
Auf G., Jabouille A., Delugin M., Guérit S., Pineau R., North S., Platonova N., Maitre M., Favereaux A., Seno M., Bikfalvi A., Minchenko D., Minchenko O., Moenner M. High epiregulin expression in human U87 glioma cells relies on IRE1 and promotes autocrine growth through EGF receptor.. BMC Cancer. 2013; 13(1): 597.
Auf G., Jabouille A., Guérit S., Pineau R., Delugin M., Bouchecareilh M., Favereaux A., Maitre M., Gaiser T., von Deimling A., Czabanka M., Vajkoczy P., Chevet E., Bikfalvi A., Moenner M. A shift from an angiogenic to invasive phenotype induced in malignant glioma by inhibition of the unfolded protein response sensor IRE1.. Proc. Natl. Acad. Sci. U.S.A. 2010; 107(35): 1555–15558.
Bakalets T., Minchenko D., Danilovskyi S., Minchenko O. Expression of protein kinase PLK family genes in U87 glioma cell line with suppressed function of ERN1 signaling enzyme of endoplasmic reticulum stress.. Visnyk Taras Shevchenko Kyiv National University. Biology. 2013; 63: 7–13.
Basu R., Barosa C., Basu A, Pattan V, Saad A, Jones J, Rizza R. Transaldolase exchange and its effects on measurements of gluconeogenesis in humans.. Am. J. Physiol. Endocrinol. Metab. 2011; 300(2): E296-E303.
Berry G.T. The unexplored potential of the pentose phosphate pathway in health and disease.. J. Inherit. Metab. Dis. 2008; 31(6): 661.
Bi M., Naczki C., Koritzinsky M., Fels D., Blais J., Hu N., Harding H., Novoa I., Varia M., Raleigh J., Scheuner D., Kaufman R.J., Bell J., Ron D., Wouters B.G., Koumenis C. ER stress-regulated translation increases tolerance to extreme hypoxia and promotes tumor growth.. EMBO J. 2005; 24(19): 3470–34815.
Drogat B., Auguste P., Nguyen D.T., Bouchecareilh M., Pineau R., Nalbantoglu J., Kaufman R.J., Chevet E., Bikfalvi A., Moenner M. IRE1 signaling is essential for ischemia-induced vascular endothelial growth factor-A expression and contributes to angiogenesis and tumor growth in vivo.. Cancer Res. 2007; 67: 6700–6707.
Du W., Jiang P., Mancuso A., Stonestrom A., Brewer M.D., Minn A.J., Mak T.W., Wu M., Yang X. TAp73 enhances the pentose phosphate pathway and supports cell proliferation.. Nat. Cell Biol. 2013; 15(8): 991–1000.
Fairbank M., St-Pierre P., Nabi I.R. The complex biology of autocrine motility factor/phosphoglucose isomerase (AMF/PGI) and its receptor, the gp78/AMFR E3 ubiquitin ligase. Mol. Biosyst. 2009; 5(8): 793–801.
Fels D.R., Koumenis C. The PERK/eIF2a/ATF4 module of the UPR in hypoxia resistance and tumor growth.. Cancer Biology & Therapy. 2006; 5(7): 723–728.
Fu M., Li L., Albrecht T., Johnson J.D., Kojic L.D., Nabi I.R. Autocrine motility factor phosphoglucose isomerase regulates ER stress and cell death through control of ER calcium release.. Cell Death Differ. 2011; 18(6): 1057–1070.
Funasaka T., Hogan V., Raz A. Phosphoglucose isomerase/autocrine motility factor mediates epithelial and mesenchymal phenotype conversions in breast cancer.. Cancer Res. 2009; 69(13): 5349–5356.
Garmash I.,Kompaniets D., Hubenia O., Minchenko D. Effect of hypoxia and glucose or glutamine deprivation on the expression of enolase and aldolase genes in glioma U87 cell line with suppressed function of ERN1 signaling enzyme.. Visnyk Taras Shevchenko Kyiv National Univ. Problems of the Regulation of Physiological Functions. 2013; 16: 5–9.
Hetz C., Chevet E., Harding H.P. Targeting the unfolded protein response in disease.. Nat. Rev. Drug Discov. 2013; 12(9): 703–719.
Hollien J., Lin J.H., Li H., Stevens N., Walter P., Weissman J. S. Regulated Ire1-dependent decay of messenger RNAs in mammalian cells.. J. Cell. Biol. 2009; 186(3): 323–331.
Hu T., Zhang C., Tang Q., Su Y., Li B., Chen L., Zhang Z., Cai T., Zhu Y. Variant G6PD levels promote tumor cell proliferation or apoptosis via the STAT3/5 pathway in the human melanoma xenograft mouse model. BMC Cancer. 2013; 13: 251р.
Kho D.H., Nangia-Makker P., Balan V., Hogan V., Tait L., Wang Y., Raz A. Autocrine motility factor promotes HER2 cleavage and signaling in breast cancer cells.. Cancer Res. 2013; 73(4): 1411–1419.
Jiang P., Du W., Yang X. A critical role of glucose-6-phosphate dehydrogenase in TAp73-mediated cell proliferation.. Cell Cycle. 2013; 12(24): 3720–3726.
Korennykh A.V., Egea P.F., Korostelev A.A., Finer-Moore J., Zhang C., Shokat K.M., Stroud R.M., Walter P. The unfolded protein response signals through high-order assembly of Ire1.. Nature. 2009; 457(7230): 687–693.
Lee J., Sun C., Zhou Y., Lee J., Gokalp D., Herrema H., Park S.W., Davis R.J., Ozcan U. p38 MAPK-mediated regulation of Xbp1s is crucial for glucose homeostasis.. Nature Medicine. 2011; 17(10): 1251–1260.
Minchenko D.O., Garmash I.A., Bashta Y.M., Kustkova G.S., Zalesna Y.D., Bikfalvi A., Minchenko O.H. ERN1 dependent expression of phosphoribosyl pyrophosphate synthetase genes in U87 glioma cells: effect of glucose or glutamine deprivation.. Int. J. Genomic Med. 2013; 1(1): 104(1–5).
Minchenko D., Hubenya O., Terletsky B., Kuznetsova A., Moenner M., Minchenko O. Blockade of the endoplasmic reticulum stress sensor inositol requiring enzyme-1 changes the expression of cyclin and growth arrest-specific genes in glioma cells.. Annales Universitatis Mariae Curie-Sklodowska. 2010; 23(3): 179–184.
Minchenko D.O., Karbovskyi L.L., Danilovskyi S.V., Kharkova A.P., Minchenko O.H. Expression of casein kinase genes in glioma cell line U87: effect of hypoxia and glucose or glutamine deprivation.. Nat. Sci. 2012a; 4(1): 38–46.
Minchenko D.O., Karbovskyi L.L., Danilovskyi S.V., Moenner M., Minchenko O.H. Effect of hypoxia and glutamine or glucose deprivation on the expression of retinoblastoma and retinoblastoma-related genes in ERN1 knockdown glioma U87 cell line.. Am. J. Mol. Biol. 2012b; 2(1): 21–31.
Minchenko O.H., Kubaichuk K.I., Minchenko D.O., Kovalevska O.V., Kulinich A.O., Lypova N.M. Molecular mechanisms of ERN1-mediated angiogenesis. Int. J. Physiol. Pathophysiol. 2014; 5(1): 1–22.
Minchenko D.О., Kubajchuk К.І., Ratushna O.O., Komisarenko S.V., Minchenko O.H. The effect of hypoxia and ischemic condition on the expression of VEGF genes in glioma U87 cells is dependent from ERN1 knockdown.. Adv. Biol. Chem. 2012c; 2(2): 198–206.
Moenner M., Pluquet O., Bouchecareilh M., Chevet E. Integrated endoplasmic reticulum stress responses in cancer.. Cancer Res. 2007; 67(22): 10631–10634.
Niinaka Y., Harada K., Fujimuro M., Oda M., Haga A., Hosoki M., Uzawa N., Arai N., Yamaguchi S., Yamashiro M., Raz A. Silencing of autocrine motility factor induces mesenchymal-to-epithelial transition and suppression of osteosarcoma pulmonary metastasis. Cancer Res. 2010; 70(22): 9483-9493.
Pan S., World C.J., Kovacs C.J., Berk B.C. Glucose 6-phosphate dehydrogenase is regulated through c-Src-mediated tyrosine phosphorylation in endothelial cells.. Arterioscler. Thromb. Vasc. Biol. 2009; 29(6): 895–901.
Pluquet O., Dejeans N., Bouchecareilh M., Lhomond S., Pineau R., Higa A., Delugin M., Combe C., Loriot S., Cubel G., Dugot-Senant N., Vital A., Loiseau H., Gosline S.J., Taouji S., Hallett M., Sarkaria J.N., Anderson K., Wu W., Rodriguez F.J., Rosenbaum J., Saltel F., Fernandez-Zapico M.E., Chevet E. Posttranscriptional regulation of PER1 underlies the oncogenic function of IREα.. Cancer Res. 2013; 73(15): 4732–4743.
Qian Y., Banerjee S., Grossman C.E., Amidon W., Nagy G., Barcza M., Niland B., Karp D.R., Middleton F.A., Banki K., Perl A. Transaldolase deficiency influences the pentose phosphate pathway, mitochondrial homoeostasis and apoptosis signal processing.. Biochem. J. 2008; 415(1): 123-134.
Romero-Ramirez L., Cao H., Nelson D., Hammond E., Lee A.H., Yoshida H., Mori K., Glimcher L.H., Denko N.C., Giaccia A.J., Le Q.-T., Koong A.C. XBP1 is essential for survival under hypoxic conditions and is required for tumor growth.. Cancer Res. 2004; 64(17): 5943–5947.
Samland A.K., Sprenger G.A. Transaldolase: from biochemistry to human disease.. Int. J. Biochem. Cell. Biol. 2009; 41(7): 1482–1494.
Shelton P., Jaiswal A.K. The transcription factor NF-E2-related factor 2 (Nrf2): a protooncogene FASEB J. 2013; 27(2): 414-423.
Stanton R.C. Glucose-6-phosphate dehydrogenase, NADPH, and cell survival. IUBMB Life. 2012; 64(5): 362–369.
Tsutsumi S., Fukasawa T., Yamauchi H., Kato T., Kigure W., Morita H., Asao T., Kuwano H. Phosphoglucose isomerase enhances colorectal cancer metastasis.. Int. J. Oncol. 2009; 35(5): 1117–1121.
Wamelink M.M., Struys E.A., Jakobs C. The biochemistry, metabolism and inherited defects of the pentose phosphate pathway: a review.. J. Inherit. Metab. Dis. 2008; 31(6): 703–717.
Zhang K., Kaufman R.J. The unfolded protein response: a stress signaling pathway critical for health and disease.. Neurology. 2006; 66(2) (Suppl 1): 102–109.
Zhou Y., Lee J., Reno C.M., Sun C., Park S.W., Chung J., Lee J., Fisher S.J., White M.F., Biddinger S.B., Ozcan U. Regulation of glucose homeostasis through a XBP-1-FoxO1 interaction.. Nature Medicine. 2011; 17(3): 356–365.
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Опубліковано
2014-06-30
Номер
Розділ
БІОХІМІЯ, БІОТЕХНОЛОГІЯ, МОЛЕКУЛЯРНА ГЕНЕТИКА
