PDK4 protein promotes tumorigenesis through activation of cAMP-response element-binding protein (CREB)-Ras homolog enriched in brain (RHEB)-mTORC1 signaling cascade

Journal of Biological Chemistry

Volumn 289, Issue 43, 2014, Pages 29739-29749

  Liu, Zhibo ^a   Chen, Xinxin ^a   Wang, Ying ^a,b   Peng, Haiyong ^a   Wang, Yanan ^a   Jing, Yanling ^a   Zhang, Hongbing ^a  

^a Postdoctoral Research Station Institute of Basic Medicine Sciences CAMS and PUMC   (China)

^b DALIAN MEDICAL UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBIOTICS; CELL CULTURE; CELL PROLIFERATION; CHEMICAL ACTIVATION; DISEASES; ENZYMES; TUMORS;

AMP-ACTIVATED PROTEIN KINASE; CAMP-RESPONSE ELEMENT-BINDING PROTEINS; HYPOXIA INDUCIBLE FACTOR 1-ALPHA; INTRACELLULAR SIGNALS; PHYSIOLOGICAL PROCESS; PYRUVATE DEHYDROGENASE KINASE; SYNERGISTIC INHIBITION; TARGET OF RAPAMYCIN;

CELLS;

CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; HYPOXIA INDUCIBLE FACTOR 1ALPHA; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; PYRUVATE DEHYDROGENASE KINASE 4; PYRUVATE KINASE; PYRUVATE KINASE ISOZYME M2; RAPAMYCIN; RHEB PROTEIN; TUBERIN; UNCLASSIFIED DRUG; DICHLOROACETIC ACID; ISOENZYME; MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1; MONOMERIC GUANINE NUCLEOTIDE BINDING PROTEIN; MULTIPROTEIN COMPLEX; NEUROPEPTIDE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE; PROTEIN KINASE B; RHEB PROTEIN, MOUSE; TARGET OF RAPAMYCIN KINASE; TUMOR SUPPRESSOR PROTEIN;

AEROBIC GLYCOLYSIS; AEROBIC METABOLISM; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CANCER INHIBITION; CARCINOGENESIS; CELL PROLIFERATION ASSAY; CHROMATIN IMMUNOPRECIPITATION; GENE SILENCING; GLYCOLYSIS; HISTOPATHOLOGY; IMMUNOHISTOCHEMISTRY; MOUSE; MTT ASSAY; NONHUMAN; PROTEIN BINDING; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; QUANTITATIVE ANALYSIS; REAL TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTION; RNA INTERFERENCE; SIGNAL TRANSDUCTION; TRANSACTIVATION; UPREGULATION; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL PROLIFERATION; DRUG EFFECTS; GENETIC TRANSCRIPTION; HEK293 CELL LINE; HUMAN; METABOLISM; NUDE MOUSE; PATHOLOGY; TUMOR CELL LINE;

AEROBIOSIS; AMP-ACTIVATED PROTEIN KINASES; ANIMALS; CARCINOGENESIS; CELL LINE, TUMOR; CELL PROLIFERATION; CYCLIC AMP RESPONSE ELEMENT-BINDING PROTEIN; DICHLOROACETIC ACID; GLYCOLYSIS; HEK293 CELLS; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; ISOENZYMES; MICE; MICE, NUDE; MONOMERIC GTP-BINDING PROTEINS; MULTIPROTEIN COMPLEXES; NEUROPEPTIDES; PROTEIN KINASES; PROTO-ONCOGENE PROTEINS C-AKT; PTEN PHOSPHOHYDROLASE; PYRUVATE KINASE; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES; TRANSCRIPTION, GENETIC; TUMOR SUPPRESSOR PROTEINS; UP-REGULATION;

EID: 84908191969     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M114.584821     Document Type: Article

References (43)

1. Laplante, M., and Sabatini, D. M. (2012) mTOR signaling in growth control and disease. Cell 149, 274-293
2. Ma, J., Meng, Y., Kwiatkowski, D. J., Chen, X., Peng, H., Sun, Q., Zha, X., Wang, F., Wang, Y., Jing, Y., Zhang, S., Chen, R., Wang, L., Wu, E., Cai, G., Malinowska-Kolodziej, I., Liao, Q., Liu, Y., Zhao, Y., Sun, Q., Xu, K., Dai, J., Han, J., Wu, L., Zhao, R. C., Shen, H., and Zhang, H. (2010) Mammalian target of rapamycin regulates murine and human cell differentiation through STAT3/p63/Jagged/Notch cascade. J. Clin. Invest. 120, 103-114
3. Wullschleger, S., Loewith, R., and Hall, M. N. (2006) TOR signaling in growth and metabolism. Cell 124, 471-484
4. Zoncu, R., Efeyan, A., and Sabatini, D. M. (2011) mTOR: from growth signal integration to cancer, diabetes and ageing. Nat. Rev. Mol. Cell Biol. 12, 21-35
5. Shah, O. J., Wang, Z., and Hunter, T. (2004) Inappropriate activation of the TSC/Rheb/mTOR/S6K cassette induces IRS1/2 depletion, insulin resistance, and cell survival deficiencies. Curr. Biol. 14, 1650-1656
6. Zhang, H., Bajraszewski, N., Wu, E., Wang, H., Moseman, A. P., Dabora, S. L., Griffin, J. D., and Kwiatkowski, D. J. (2007) PDGFRs are critical for PI3K/Akt activation and negatively regulated by mTOR. J. Clin. Invest. 117, 730-738
7. 2+ entry constrains tuberous sclerosis complex-related tumor development. Oncogene 32, 4702-4711
8. Yu, Y., Yoon, S. O., Poulogiannis, G., Yang, Q., Ma, X. M., Villén, J., Kubica, N., Hoffman, G. R., Cantley, L. C., Gygi, S. P., and Blenis, J. (2011) Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling. Science 332, 1322-1326
9. Kwiatkowski, D. J., Zhang, H., Bandura, J. L., Heiberger, K. M., Glogauer, M., el-Hashemite, N., and Onda, H. (2002) A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in Tsc1 null cells. Hum. Mol. Genet. 11, 525-534
10. Tee, A. R., Fingar, D. C., Manning, B. D., Kwiatkowski, D. J., Cantley, L. C., and Blenis, J. (2002) Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling. Proc. Natl. Acad. Sci. U.S.A. 99, 13571-13576
11. Potter, C. J., Pedraza, L. G., and Xu, T. (2002) Akt regulates growth by directly phosphorylating Tsc2. Nat Cell Biol. 4, 658-665
12. Inoki, K., Li, Y., Zhu, T., Wu, J., and Guan, K. L. (2002) TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat. Cell Biol. 4, 648-657
13. Inoki, K., Zhu, T., and Guan, K. L. (2003) TSC2 mediates cellular energy response to control cell growth and survival. Cell 115, 577-590
14. Hay, N., and Sonenberg, N. (2004) Upstream and downstream of mTOR. Genes Dev. 18, 1926-1945
15. Kim, J., Kundu, M., Viollet, B., and Guan, K. L. (2011) AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat. Cell Biol. 13, 132-141
16. Yecies, J. L., and Manning, B. D. (2011) Transcriptional control of cellular metabolism by mTOR signaling. Cancer Res. 71, 2815-2820
17. Ma, J., Sun, Q., Mi, R., and Zhang, H. (2011) Avian influenza A virus H5N1 causes autophagy-mediated cell death through suppression of mTOR signaling. J. Genet. Genomics 38, 533-537
18. Hudson, C. C., Liu, M., Chiang, G. G., Otterness, D. M., Loomis, D. C., Kaper, F., Giaccia, A. J., and Abraham, R. T. (2002) Regulation of hypoxia-inducible factor 1α expression and function by the mammalian target of rapamycin. Mol. Cell. Biol. 22, 7004-7014
19. Sun, Q., Chen, X., Ma, J., Peng, H., Wang, F., Zha, X., Wang, Y., Jing, Y., Yang, H., Chen, R., Chang, L., Zhang, Y., Goto, J., Onda, H., Chen, T., Wang, M. R., Lu, Y., You, H., Kwiatkowski, D., and Zhang, H. (2011) Mammalian target of rapamycin up-regulation of pyruvate kinase isoenzyme type M2 is critical for aerobic glycolysis and tumor growth. Proc. Natl. Acad. Sci. U.S.A. 108, 4129-4134
20. Guertin, D. A., and Sabatini, D. M. (2007) Defining the role of mTOR in cancer. Cancer Cell 12, 9-22
21. Holness, M. J., and Sugden, M. C. (2003) Regulation of pyruvate dehydrogenase complex activity by reversible phosphorylation. Biochem. Soc. Trans. 31, 1143-1151
22. Bowker-Kinley, M. M., Davis, W. I., Wu, P., Harris, R. A., and Popov, K. M. (1998) Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complex. Biochem. J. 329, 191-196
23. Stacpoole, P. W., Kurtz, T. L., Han, Z., and Langaee, T. (2008) Role of dichloroacetate in the treatment of genetic mitochondrial diseases. Adv. Drug Deliv. Rev. 60, 1478-1487
24. Michelakis, E. D., Sutendra, G., Dromparis, P., Webster, L., Haromy, A., Niven, E., Maguire, C., Gammer, T. L., Mackey, J. R., Fulton, D., Abdulkarim, B., McMurtry, M. S., and Petruk, K. C. (2010) Metabolic modulation of glioblastoma with dichloroacetate. Sci. Transl. Med. 2, 31ra34
25. Meric-Bernstam, F., and Gonzalez-Angulo, A. M. (2009) Targeting the mTOR signaling network for cancer therapy. J. Clin. Oncol. 27, 2278-2287
26. Kobayashi, T., Hirayama, Y., Kobayashi, E., Kubo, Y., and Hino, O. (1995) A germline insertion in the tuberous sclerosis (Tsc2) gene gives rise to the Eker rat model of dominantly inherited cancer. Nat. Genet. 9, 70-74
27. Zheng, M., Wang, Y. H., Wu, X. N., Wu, S. Q., Lu, B. J., Dong, M. Q., Zhang, H., Sun, P., Lin, S. C., Guan, K. L., and Han, J. (2011) Inactivation of Rheb by PRAK-mediated phosphorylation is essential for energy-depletion-induced suppression of mTORC1. Nat. Cell Biol. 13, 263-272
28. McFate, T., Mohyeldin, A., Lu, H., Thakar, J., Henriques, J., Halim, N. D., Wu, H., Schell, M. J., Tsang, T. M., Teahan, O., Zhou, S., Califano, J. A., Jeoung, N. H., Harris, R. A., and Verma, A. (2008) Pyruvate dehydrogenase complex activity controls metabolic and malignant phenotype in cancer cells. J. Biol. Chem. 283, 22700-22708
29. Li, Y., Wang, Y., Kim, E., Beemiller, P., Wang, C. Y., Swanson, J., You, M., and Guan, K. L. (2007) Bnip3 mediates the hypoxia-induced inhibition on mammalian target of rapamycin by interacting with Rheb. J. Biol. Chem. 282, 35803-35813
30. Long, X., Lin, Y., Ortiz-Vega, S., Yonezawa, K., and Avruch, J. (2005) Rheb binds and regulates the mTOR kinase. Curr. Biol. 15, 702-713
31. Schewe, D. M., and Aguirre-Ghiso, J. A. (2008) ATF6α-Rheb-mTOR signaling promotes survival of dormant tumor cells in vivo. Proc. Natl. Acad. Sci. U.S.A. 105, 10519-10524
32. Montminy, M. R., and Bilezikjian, L. M. (1987) Binding of a nuclear protein to the cyclic-AMP response element of the somatostatin gene. Nature 328, 175-178
33. Mayr, B., and Montminy, M. (2001) Transcriptional regulation by the phosphorylation-dependent factor CREB. Nat. Rev. Mol. Cell Biol. 2, 599-609
34. Guo, L., Xie, B., and Mao, Z. (2012) Autophagy in premature senescent cells is activated via AMPK pathway. Int. J. Mol. Sci. 13, 3563-3582
35. Downward, J. (1998) Mechanisms and consequences of activation of protein kinase B/Akt. Curr. Opin. Cell Biol. 10, 262-267
36. Shackelford, D. B., and Shaw, R. J. (2009) The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat. Rev. Cancer 9, 563-575
37. Tee, A. R., Anjum, R., and Blenis, J. (2003) Inactivation of the tuberous sclerosis complex-1 and -2 gene products occurs by phosphoinositide 3-kinase/Akt-dependent and -independent phosphorylation of tuberin. J. Biol. Chem. 278, 37288-37296
38. Garami, A., Zwartkruis, F. J., Nobukuni, T., Joaquin, M., Roccio, M., Stocker, H., Kozma, S. C., Hafen, E., Bos, J. L., and Thomas, G. (2003) Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2. Mol. Cell 11, 1457-1466
39. Zhang, H., Cicchetti, G., Onda, H., Koon, H. B., Asrican, K., Bajraszewski, N., Vazquez, F., Carpenter, C. L., and Kwiatkowski, D. J. (2003) Loss of Tsc1/Tsc2 activates mTOR and disrupts PI3K-Akt signaling through downregulation of PDGFR. J. Clin. Invest. 112, 1223-1233
40. Comerford, K. M., Leonard, M. O., Karhausen, J., Carey, R., Colgan, S. P., and Taylor, C. T. (2003) Small ubiquitin-related modifier-1 modification mediates resolution of CREB-dependent responses to hypoxia. Proc. Natl. Acad. Sci. U.S.A. 100, 986-991
41. Mu, J., Ostrowski, R. P., Soejima, Y., Rolland, W. B., Krafft, P. R., Tang, J., and Zhang, J. H. (2013) Delayed hyperbaric oxygen therapy induces cell proliferation through stabilization of cAMP responsive element binding protein in the rat model of MCAo-induced ischemic brain injury. Neurobiol. Dis. 51, 133-143
42. DeAngelo, A. B., Daniel, F. B., Stober, J. A., and Olson, G. R. (1991) The carcinogenicity of dichloroacetic acid in the male B6C3F1 mouse. Fundam. Appl. Toxicol. 16, 337-347
43. Stacpoole, P. W., Henderson, G. N., Yan, Z., and James, M. O. (1998) Clinical pharmacology and toxicology of dichloroacetate. Environ. Health Perspect. 106, 989-994