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Genes & Dev. 15 (11): 1406-1418

Copyright © 2001 by Cold Spring Harbor Laboratory Press.

Vol. 15, No. 11, pp. 1406-1418, June 1, 2001

Inhibition of early apoptotic events by Akt/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase

Kathrin Gottlob,1 Nathan Majewski,1 Scott Kennedy,1,4 Eugene Kandel,1 R. Brooks Robey,2,3 and Nissim Hay1,5

1 Department of Molecular Genetics; 2 Department of Medicine, University of Illinois at Chicago, Chicago, Illinois 60607, USA; 3 Veterans Administration, Chicago Healthcare System, West Side Division, Chicago, Illinois 60607, USA

The serine/threonine kinase Akt/PKB is a major downstream effector of growth factor-mediated cell survival. Activated Akt, like Bcl-2 and Bcl-xL, prevents closure of a PT pore component, the voltage-dependent anion channel (VDAC); intracellular acidification; mitochondrial hyperpolarization; and the decline in oxidative phosphorylation that precedes cytochrome c release. However, unlike Bcl-2 and Bcl-xL, the ability of activated Akt to preserve mitochondrial integrity, and thereby inhibit apoptosis, requires glucose availability and is coupled to its metabolism. Hexokinases are known to bind to VDAC and directly couple intramitochondrial ATP synthesis to glucose metabolism. We provide evidence that such coupling serves as a downstream effector function for Akt. First, Akt increases mitochondria-associated hexokinase activity. Second, the antiapoptotic activity of Akt requires only the first committed step of glucose metabolism catalyzed by hexokinase. Finally, ectopic hexokinase expression mimics the ability of Akt to inhibit cytochrome c release and apoptosis. We therefore propose that Akt increases coupling of glucose metabolism to oxidative phosphorylation and regulates PT pore opening via the promotion of hexokinase-VDAC interaction at the outer mitochondrial membrane.

[Key Words: Mitochondrial potential; cytochrome c; ATP; Bcl-2; Bcl-xL]

4 Present address: Department of Molecular Biology, MGH and Harvard Medical School, Boston, MA 02114, USA.

5 Corresponding author.

GENES & DEVELOPMENT 15:1406-1418 © 2001 by Cold Spring Harbor Laboratory Press  ISSN 0890-9369/01 $5.00

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   Abstract »    Full Text »    PDF »
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H. Yeo, C. A. Lyssiotis, Y. Zhang, H. Ying, J. M. Asara, L. C. Cantley, and J.-H. Paik (2013)
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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J. Biol. Chem. 288, 25007-25024
   Abstract »    Full Text »    PDF »
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D. J. Roberts, V. P. Tan-Sah, J. M. Smith, and S. Miyamoto (2013)
J. Biol. Chem. 288, 23798-23806
   Abstract »    Full Text »    PDF »
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C. Betz, D. Stracka, C. Prescianotto-Baschong, M. Frieden, N. Demaurex, and M. N. Hall (2013)
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   Abstract »    Full Text »    PDF »
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W. M. Teferi, K. Dodd, R. Maranchuk, N. Favis, and D. H. Evans (2013)
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   Abstract »    Full Text »    PDF »
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P. Pasdois, J. E. Parker, E. J. Griffiths, and A. P. Halestrap (2013)
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   Abstract »    Full Text »    PDF »
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V. Balaji, J. Selvaraj, S. Sathish, C. Mayilvanan, and K. Balasubramanian (2013)
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   Abstract »    Full Text »    PDF »
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P. Pasdois, J. E. Parker, and A. P. Halestrap (2012)
JAHA 2, e005645
   Abstract »    Full Text »    PDF »
Mitochondrial localization of TIGAR under hypoxia stimulates HK2 and lowers ROS and cell death.
E. C. Cheung, R. L. Ludwig, and K. H. Vousden (2012)
PNAS 109, 20491-20496
   Abstract »    Full Text »    PDF »
Cancer Cell Metabolism: One Hallmark, Many Faces.
J. R. Cantor and D. M. Sabatini (2012)
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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E. Bobrovnikova-Marjon, D. Pytel, M. J. Riese, L. P. Vaites, N. Singh, G. A. Koretzky, E. S. Witze, and J. A. Diehl (2012)
Mol. Cell. Biol. 32, 2268-2278
   Abstract »    Full Text »    PDF »
Rab25 increases cellular ATP and glycogen stores protecting cancer cells from bioenergetic stress.
K. W. Cheng, R. Agarwal, S. Mitra, J.-S. Lee, M. Carey, J. W. Gray, and G. B. Mills (2012)
EMBO Mol Med. 4, 125-141
   Abstract »    Full Text »    PDF »
Mitochondrial hexokinase II (HKII) and phosphoprotein enriched in astrocytes (PEA15) form a molecular switch governing cellular fate depending on the metabolic state.
P. Mergenthaler, A. Kahl, A. Kamitz, V. van Laak, K. Stohlmann, S. Thomsen, H. Klawitter, I. Przesdzing, L. Neeb, D. Freyer, et al. (2012)
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   Abstract »    Full Text »    PDF »
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R. J. Walker, N. M. Anderson, Y. Jiang, S. Bahouth, and J. J. Steinle (2011)
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   Abstract »    Full Text »    PDF »
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C. A. Goodman, J. W. Frey, D. M. Mabrey, B. L. Jacobs, H. C. Lincoln, J.-S. You, and T. A. Hornberger (2011)
J. Physiol. 589, 5485-5501
   Abstract »    Full Text »    PDF »
Glycolytic rate and lymphomagenesis depend on PARP14, an ADP ribosyltransferase of the B aggressive lymphoma (BAL) family.
S. H. Cho, A. K. Ahn, P. Bhargava, C.-H. Lee, C. M. Eischen, O. McGuinness, and M. Boothby (2011)
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   Abstract »    Full Text »    PDF »
Disruption of Hexokinase II-Mitochondrial Binding Blocks Ischemic Preconditioning and Causes Rapid Cardiac Necrosis.
K. M. A. Smeele, R. Southworth, R. Wu, C. Xie, R. Nederlof, A. Warley, J. K. Nelson, P. van Horssen, J. P. van den Wijngaard, S. Heikkinen, et al. (2011)
Circ. Res. 108, 1165-1169
   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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J. Exp. Med. 208, 313-326
   Abstract »    Full Text »    PDF »
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P. Tandon, C. A. Gallo, S. Khatri, J. F. Barger, H. Yepiskoposyan, and D. R. Plas (2011)
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   Abstract »    Full Text »    PDF »
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Cold Spring Harb Symp Quant Biol 76, 375-387
   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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S. Y. Nam, H. H. Seo, H. S. Park, S. An, J.-Y. Kim, K. H. Yang, C. S. Kim, M. Jeong, and Y.-W. Jin (2010)
J. Biol. Chem. 285, 31157-31163
   Abstract »    Full Text »    PDF »
Balancing biosynthesis and bioenergetics: metabolic programs in oncogenesis.
J. F. Barger and D. R. Plas (2010)
Endocr. Relat. Cancer 17, R287-R304
   Abstract »    Full Text »    PDF »
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J. Biol. Chem. 285, 17673-17680
   Abstract »    Full Text »    PDF »
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   Abstract »    PDF »
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   Abstract »    Full Text »    PDF »
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M. M. Juntilla, V. D. Patil, M. Calamito, R. P. Joshi, M. J. Birnbaum, and G. A. Koretzky (2010)
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   Abstract »    Full Text »    PDF »
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Y. Fan, K. G. Dickman, and W.-X. Zong (2010)
J. Biol. Chem. 285, 7324-7333
   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
The Akt isoforms are present at distinct subcellular locations.
S. A. Santi and H. Lee (2010)
Am J Physiol Cell Physiol 298, C580-C591
   Abstract »    Full Text »    PDF »
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J. Biol. Chem. 284, 26816-26830
   Abstract »    Full Text »    PDF »
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P. T. Bhaskar, V. Nogueira, K. C. Patra, S.-M. Jeon, Y. Park, R. B. Robey, and N. Hay (2009)
Mol. Cell. Biol. 29, 5136-5147
   Abstract »    Full Text »    PDF »
Evaluation of the Role of Hexokinase Type II in Cellular Proliferation and Apoptosis Using Human Hepatocellular Carcinoma Cell Lines.
K. J. Ahn, H. S. Hwang, J. H. Park, S. H. Bang, W. J. Kang, M. Yun, and J. D. Lee (2009)
J. Nucl. Med. 50, 1525-1532
   Abstract »    Full Text »    PDF »
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Arterioscler Thromb Vasc Biol 29, 1283-1289
   Abstract »    Full Text »    PDF »
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D. A. Tennant, R. V. Duran, H. Boulahbel, and E. Gottlieb (2009)
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   Abstract »    Full Text »    PDF »
Ischemic preconditioning affects hexokinase activity and HKII in different subcellular compartments throughout cardiac ischemia-reperfusion.
E. Gurel, K. M. Smeele, O. Eerbeek, A. Koeman, C. Demirci, M. W. Hollmann, and C. J. Zuurbier (2009)
J Appl Physiol 106, 1909-1916
   Abstract »    Full Text »    PDF »
Nuclear and mitochondrial signalling Akts in cardiomyocytes.
S. Miyamoto, M. Rubio, and M. A. Sussman (2009)
Cardiovasc Res 82, 272-285
   Abstract »    Full Text »    PDF »
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W. Wang, A. Fridman, W. Blackledge, S. Connelly, I. A. Wilson, R. B. Pilz, and G. R. Boss (2009)
J. Biol. Chem. 284, 3521-3528
   Abstract »    Full Text »    PDF »
Voltage-dependent Anion Channel 1-based Peptides Interact with Hexokinase to Prevent Its Anti-apoptotic Activity.
L. Arzoine, N. Zilberberg, R. Ben-Romano, and V. Shoshan-Barmatz (2009)
J. Biol. Chem. 284, 3946-3955
   Abstract »    Full Text »    PDF »
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J. Camacho-Pereira, L. E. Meyer, L. B. Machado, M. F. Oliveira, and A. Galina (2009)
Plant Physiology 149, 1099-1110
   Abstract »    Full Text »    PDF »
Glucose Metabolism Attenuates p53 and Puma-dependent Cell Death upon Growth Factor Deprivation.
Y. Zhao, J. L. Coloff, E. C. Ferguson, S. R. Jacobs, K. Cui, and J. C. Rathmell (2008)
J. Biol. Chem. 283, 36344-36353
   Abstract »    Full Text »    PDF »
Stress-Induced Cell Death Is Mediated by Ceramide Synthesis in Neurospora crassa.
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   Abstract »    Full Text »    PDF »
Gastrin-releasing peptide receptor silencing suppresses the tumorigenesis and metastatic potential of neuroblastoma.
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   Abstract »    Full Text »    PDF »
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H. Deng, F. Yu, J. Chen, Y. Zhao, J. Xiang, and A. Lin (2008)
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   Abstract »    Full Text »    PDF »
Hexokinase-I Protection against Apoptotic Cell Death Is Mediated via Interaction with the Voltage-dependent Anion Channel-1: MAPPING THE SITE OF BINDING.
S. Abu-Hamad, H. Zaid, A. Israelson, E. Nahon, and V. Shoshan-Barmatz (2008)
J. Biol. Chem. 283, 13482-13490
   Abstract »    Full Text »    PDF »
FOXO3A Regulates Peroxiredoxin III Expression in Human Cardiac Fibroblasts.
C. B. Chiribau, L. Cheng, I. C. Cucoranu, Y.-S. Yu, R. E. Clempus, and D. Sorescu (2008)
J. Biol. Chem. 283, 8211-8217
   Abstract »    Full Text »    PDF »
Txnip balances metabolic and growth signaling via PTEN disulfide reduction.
S. T. Y. Hui, A. M. Andres, A. K. Miller, N. J. Spann, D. W. Potter, N. M. Post, A. Z. Chen, S. Sachithanantham, D. Y. Jung, J. K. Kim, et al. (2008)
PNAS 105, 3921-3926
   Abstract »    Full Text »    PDF »
Pharmacological and Clinical Aspects of Heme Oxygenase.
N. G. Abraham and A. Kappas (2008)
Pharmacol. Rev. 60, 79-127
   Abstract »    Full Text »    PDF »
Multiple antiapoptotic targets of the PI3K/Akt survival pathway are activated by epoxyeicosatrienoic acids to protect cardiomyocytes from hypoxia/anoxia.
A. Dhanasekaran, S. K. Gruenloh, J. N. Buonaccorsi, R. Zhang, G. J. Gross, J. R. Falck, P. K. Patel, E. R. Jacobs, and M. Medhora (2008)
Am J Physiol Heart Circ Physiol 294, H724-H735
   Abstract »    Full Text »    PDF »
Heart mitochondria: gates of life and death.
A. B. Gustafsson and R. A. Gottlieb (2008)
Cardiovasc Res 77, 334-343
   Abstract »    Full Text »    PDF »
Genes in Glucose Metabolism and Association With Spina Bifida.
C. M. Davidson, H. Northrup, T. M. King, J. M. Fletcher, I. Townsend, G. H. Tyerman, and Kit Sing Au (2008)
Reproductive Sciences 15, 51-58
   Abstract »    PDF »
Hypoxia-Inducible Factor 1 and Dysregulated c-Myc Cooperatively Induce Vascular Endothelial Growth Factor and Metabolic Switches Hexokinase 2 and Pyruvate Dehydrogenase Kinase 1.
J.-w. Kim, P. Gao, Y.-C. Liu, G. L. Semenza, and C. V. Dang (2007)
Mol. Cell. Biol. 27, 7381-7393
   Abstract »    Full Text »    PDF »
Decreased lactation capacity and altered milk composition in insulin receptor substrate null mice is associated with decreased maternal body mass and reduced insulin-dependent phosphorylation of mammary Akt.
D. L Hadsell, W. Olea, N. Lawrence, J. George, D. Torres, T. Kadowaki, and A. V Lee (2007)
J. Endocrinol. 194, 327-336
   Abstract »    Full Text »    PDF »
Akt1 and Akt2 are required for {alpha}beta thymocyte survival and differentiation.
M. M. Juntilla, J. A. Wofford, M. J. Birnbaum, J. C. Rathmell, and G. A. Koretzky (2007)
PNAS 104, 12105-12110
   Abstract »    Full Text »    PDF »
Energy Depletion Inhibits Phosphatidylinositol 3-Kinase/Akt Signaling and Induces Apoptosis via AMP-activated Protein Kinase-dependent Phosphorylation of IRS-1 at Ser-794.
A. Tzatsos and P. N. Tsichlis (2007)
J. Biol. Chem. 282, 18069-18082
   Abstract »    Full Text »    PDF »
Glycogen Synthase Kinase 3{alpha} and 3{beta} Mediate a Glucose-Sensitive Antiapoptotic Signaling Pathway To Stabilize Mcl-1.
Y. Zhao, B. J. Altman, J. L. Coloff, C. E. Herman, S. R. Jacobs, H. L. Wieman, J. A. Wofford, L. N. Dimascio, O. Ilkayeva, A. Kelekar, et al. (2007)
Mol. Cell. Biol. 27, 4328-4339
   Abstract »    Full Text »    PDF »
Subcellular location of serum- and glucocorticoid-induced kinase-1 in renal and mammary epithelial cells.
E. Cordas, A. Naray-Fejes-Toth, and G. Fejes-Toth (2007)
Am J Physiol Cell Physiol 292, C1971-C1981
   Abstract »    Full Text »    PDF »
Cytokine Stimulation Promotes Glucose Uptake via Phosphatidylinositol-3 Kinase/Akt Regulation of Glut1 Activity and Trafficking.
H. L. Wieman, J. A. Wofford, and J. C. Rathmell (2007)
Mol. Biol. Cell 18, 1437-1446
   Abstract »    Full Text »    PDF »
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A. Patenaude, R. G. Deschesnes, J. L.C. Rousseau, E. Petitclerc, J. Lacroix, M.-F. Cote, and R. C.-Gaudreault (2007)
Cancer Res. 67, 2306-2316
   Abstract »    Full Text »    PDF »
c-Jun NH2-Terminal Kinase-Related Na+/H+ Exchanger Isoform 1 Activation Controls Hexokinase II Expression in Benzo(a)Pyrene-Induced Apoptosis.
L. Huc, X. Tekpli, J. A. Holme, M. Rissel, A. Solhaug, C. Gardyn, G. Le Moigne, M. Gorria, M.-T. Dimanche-Boitrel, and D. Lagadic-Gossmann (2007)
Cancer Res. 67, 1696-1705
   Abstract »    Full Text »    PDF »
Loss of Mcl-1 Protein and Inhibition of Electron Transport Chain Together Induce Anoxic Cell Death.
J. K. Brunelle, E. H. Shroff, H. Perlman, A. Strasser, C. T. Moraes, R. A. Flavell, N. N. Danial, B. Keith, C. B. Thompson, and N. S. Chandel (2007)
Mol. Cell. Biol. 27, 1222-1235
   Abstract »    Full Text »    PDF »
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Am J Physiol Heart Circ Physiol 292, H378-H386
   Abstract »    Full Text »    PDF »
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R. Olszanecki, R. Rezzani, S. Omura, D. E. Stec, L. Rodella, F. T. Botros, A. I. Goodman, G. Drummond, and N. G. Abraham (2007)
Am J Physiol Renal Physiol 292, F148-F157
   Abstract »    Full Text »    PDF »
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R. J. DeBerardinis, J. J. Lum, and C. B. Thompson (2006)
J. Biol. Chem. 281, 37372-37380
   Abstract »    Full Text »    PDF »
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E. E. Dupont-Versteegden, B. A. Strotman, C. M. Gurley, D. Gaddy, M. Knox, J. D. Fluckey, and C. A. Peterson (2006)
Am J Physiol Regulatory Integrative Comp Physiol 291, R1730-R1740
   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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M. A. Di Noia, S. Van Driesche, F. Palmieri, L.-M. Yang, S. Quan, A. I. Goodman, and N. G. Abraham (2006)
J. Biol. Chem. 281, 15687-15693
   Abstract »    Full Text »    PDF »
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C.-L. M. Soltys, S. Kovacic, and J. R. B. Dyck (2006)
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   Abstract »    Full Text »    PDF »
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J. Biol. Chem. 281, 13949-13956
   Abstract »    Full Text »    PDF »
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P. J. Jensen, J. D. Gitlin, and M. O. Carayannopoulos (2006)
J. Biol. Chem. 281, 13382-13387
   Abstract »    Full Text »    PDF »
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S. T. Henderson, M. Bonafe, and T. E. Johnson (2006)
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
Glucose Withdrawal Induces Oxidative Stress followed by Apoptosis in Glioblastoma Cells but not in Normal Human Astrocytes.
N. Jelluma, X. Yang, D. Stokoe, G. I. Evan, T. B. Dansen, and D. A. Haas-Kogan (2006)
Mol. Cancer Res. 4, 319-330
   Abstract »    Full Text »    PDF »
Phosphatidylinositol 3-Kinase Activity Is Critical for Glucose Metabolism and Embryo Survival in Murine Blastocysts.
J. K. Riley, M. O. Carayannopoulos, A. H. Wyman, M. Chi, and K. H. Moley (2006)
J. Biol. Chem. 281, 6010-6019
   Abstract »    Full Text »    PDF »
Protection of HIF-1-deficient primary renal tubular epithelial cells from hypoxia-induced cell death is glucose dependent.
M. P. Biju, Y. Akai, N. Shrimanker, and V. H. Haase (2005)
Am J Physiol Renal Physiol 289, F1217-F1226
   Abstract »    Full Text »    PDF »
Glucose 6-Phosphate Release of Wild-type and Mutant Human Brain Hexokinases from Mitochondria.
D. A. Skaff, C. S. Kim, H. J. Tsai, R. B. Honzatko, and H. J. Fromm (2005)
J. Biol. Chem. 280, 38403-38409
   Abstract »    Full Text »    PDF »
Activation of Glycogen Synthase Kinase 3{beta} Disrupts the Binding of Hexokinase II to Mitochondria by Phosphorylating Voltage-Dependent Anion Channel and Potentiates Chemotherapy-Induced Cytotoxicity.
J. G. Pastorino, J. B. Hoek, and N. Shulga (2005)
Cancer Res. 65, 10545-10554
   Abstract »    Full Text »    PDF »
The matrix protein CCN1 (CYR61) induces apoptosis in fibroblasts.
V. Todorovicc, C.-C. Chen, N. Hay, and L. F. Lau (2005)
J. Cell Biol. 171, 559-568
   Abstract »    Full Text »    PDF »
Mammalian Target of Rapamycin Promotes Vincristine Resistance through Multiple Mechanisms Independent of Maintained Glycolytic Rate.
D. J. VanderWeele and C. M. Rudin (2005)
Mol. Cancer Res. 3, 635-644
   Abstract »    Full Text »    PDF »
Akt Activates the Mammalian Target of Rapamycin by Regulating Cellular ATP Level and AMPK Activity.
A. Hahn-Windgassen, V. Nogueira, C.-C. Chen, J. E. Skeen, N. Sonenberg, and N. Hay (2005)
J. Biol. Chem. 280, 32081-32089
   Abstract »    Full Text »    PDF »
Involvement of Transforming Growth Factor-{beta}1 Signaling in Hypoxia-induced Tolerance to Glucose Starvation.
A. Suzuki, G.-i. Kusakai, Y. Shimojo, J. Chen, T. Ogura, M. Kobayashi, and H. Esumi (2005)
J. Biol. Chem. 280, 31557-31563
   Abstract »    Full Text »    PDF »
K-ras Codon-Specific Mutations Produce Distinctive Metabolic Phenotypes in Human Fibroblasts.
P. Vizan, L. G. Boros, A. Figueras, G. Capella, R. Mangues, S. Bassilian, S. Lim, W.-N. P. Lee, and M. Cascante (2005)
Cancer Res. 65, 5512-5515
   Abstract »    Full Text »    PDF »
Metformin Prevents High-Glucose-Induced Endothelial Cell Death Through a Mitochondrial Permeability Transition-Dependent Process.
D. Detaille, B. Guigas, C. Chauvin, C. Batandier, E. Fontaine, N. Wiernsperger, and X. Leverve (2005)
Diabetes 54, 2179-2187
   Abstract »    Full Text »    PDF »
Localization of the GLUT8 glucose transporter in murine kidney and regulation in vivo in nondiabetic and diabetic conditions.
M. Schiffer, K. Susztak, M. Ranalletta, A. C. Raff, E. P. Bottinger, and M. J. Charron (2005)
Am J Physiol Renal Physiol 289, F186-F193
   Abstract »    Full Text »    PDF »
Ischemic preconditioning, insulin, and morphine all cause hexokinase redistribution.
C. J. Zuurbier, O. Eerbeek, and A. J. Meijer (2005)
Am J Physiol Heart Circ Physiol 289, H496-H499
   Abstract »    Full Text »    PDF »
Mitochondria and Cancer: Warburg Addressed.
D.C. WALLACE (2005)
Cold Spring Harb Symp Quant Biol 70, 363-374
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Akt up-regulation increases resistance to microtubule-directed chemotherapeutic agents through mammalian target of rapamycin.
D. J. VanderWeele, R. Zhou, and C. M. Rudin (2004)
Mol. Cancer Ther. 3, 1605-1613
   Abstract »    Full Text »    PDF »
Putting the Rap on Akt.
J. E. Thompson and C. B. Thompson (2004)
J. Clin. Oncol. 22, 4217-4226
   Abstract »    Full Text »    PDF »

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