FUSION-guided hypothesis development leads to the identification of N6,N6-dimethyladenosine, a marine-derived AKT pathway inhibitor

Marine Drugs

Volumn 15, Issue 3, 2017, Pages

  Vaden, Rachel M ^a   Oswald, Nathaniel W ^a   Potts, Malia B ^a,b   MacMillan, John B ^a   White, Michael A ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

Author keywords

AKT; Dimethyladenosine; Functional signature ontology

Indexed keywords

6 N,N DIMETHYLADENOSINE; PROTEIN KINASE B; BIOLOGICAL PRODUCT;

ARTICLE; CONTROLLED STUDY; DRUG EFFECT; DRUG IDENTIFICATION; DRUG MECHANISM; DRUG RESPONSE; LUNG CANCER CELL LINE; NON SMALL CELL LUNG CANCER; SIGNAL TRANSDUCTION; AQUATIC SPECIES; BACTERIUM; BIOLOGICAL ONTOLOGY; CHEMISTRY; DRUG EFFECTS; HUMAN; LUNG TUMOR; METABOLISM; TUMOR CELL LINE;

AQUATIC ORGANISMS; BACTERIA; BIOLOGICAL ONTOLOGIES; BIOLOGICAL PRODUCTS; CARCINOMA, NON-SMALL-CELL LUNG; CELL LINE, TUMOR; HUMANS; LUNG NEOPLASMS; PROTO-ONCOGENE PROTEINS C-AKT; SIGNAL TRANSDUCTION;

EID: 85016501105     PISSN: None     EISSN: 16603397     Source Type: Journal    
DOI: 10.3390/md15030075     Document Type: Article

References (26)

1. Wolfender, J.-L.; Marti, G.; Thomas, A.; Bertrand, S. Current approaches and challenges for the metabolite profiling of complex natural extracts. J. Chromatogr. A 2015, 1382, 136-164. [CrossRef] [PubMed]
2. Potts, M.B.; Kim, H.S.; Fisher, K.W.; Hu, Y.; Carrasco, Y.P.; Bulut, G.B.; Ou, Y.-H.; Herrera-Herrera, M.L.; Cubillos, F.; Mendiratta, S.; et al. Using functional signature ontology (FUSION) to identify mechanisms of action for natural products. Sci. Signal. 2013, 6, ra90. [CrossRef] [PubMed]
3. Capodanno, A.; Camerini, A.; Orlandini, C.; Baldini, E.; Resta, M.L.; Bevilacqua, G.; Collecchi, P. Dysregulated PI3K/Akt/PTEN pathway is a marker of a short disease-free survival in node-negative breast carcinoma. Hum. Pathol. 2009, 40, 1408-1417. [CrossRef] [PubMed]
4. Vivanco, I.; Chen, Z.C.; Tanos, B.; Oldrini, B.; Hsieh, W.-Y.; Yannuzzi, N.; Campos, C.; Mellinghoff, I.K. A kinase-independent function of AKT promotes cancer cell survival. eLife 2014, 3, e03751. [CrossRef] [PubMed]
5. Sanidas, I.; Polytarchou, C.; Hatziapostolou, M.; Ezell, S.A.; Kottakis, F.; Hu, L.; Guo, A.; Xie, J.; Comb, M.J.; Iliopoulos, D.; et al. Phosphoproteomics screen reveals Akt isoform-specific signals linking RNA processing to lung cancer. Mol. Cell 2014, 53, 577-590. [CrossRef] [PubMed]
6. Ye, Q.; Cai,W.; Zheng, Y.; Evers, B.M.; She, Q.B. ERK and AKT signaling cooperate to translationally regulate survivin expression for metastatic progression of colorectal cancer. Oncogene 2014, 33, 1828-1839. [CrossRef] [PubMed]
7. Yue, S.; Li, J.; Lee, S.-Y.; Lee, H.J.; Shao, T.; Song, B.; Cheng, L.; Masterson, T.A.; Liu, X.; Ratliff, T.L.; et al. Cholesteryl ester accumulation induced by PTEN loss and PI3K/AKT activation underlies human prostate cancer aggressiveness. Cell Metab. 2014, 19, 393-406. [CrossRef] [PubMed]
8. Ocana, A.; Vera-Badillo, F.; Al-Mubarak, M.; Templeton, A.J.; Corrales-Sanchez, V.; Diez-Gonzalez, L.; Cuenca-Lopez, M.D.; Seruga, B.; Pandiella, A.; Amir, E. Activation of the PI3K/mTOR/AKT pathway and survival in solid tumors: Systematic review and meta-Analysis. PLoS ONE 2014, 9, e95219. [CrossRef] [PubMed]
9. Ou, Y.-H.; Torres, M.; Ram, R.; Formstecher, E.; Roland, C.; Cheng, T.; Brekken, R.; Wurz, R.; Tasker, A.; Polverino, T.; et al. TBK1 directly engages Akt/PKB survival signaling to support oncogenic transformation. Mol. Cell 2011, 41, 458-470. [CrossRef] [PubMed]
10. Alessi, D.R.; James, S.R.; Downes, C.P.; Holmes, A.B.; Gaffney, P.R.J.; Reese, C.B.; Cohen, P. Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase B-. Curr. Biol. 1997, 7, 261-269. [CrossRef]
11. Yu, J.; Zhou, X.; Chang, M.; Nakaya, M.; Chang, J.-H.; Xiao, Y.; William Lindsey, J.; Dorta-Estremera, S.; Cao, W.; Zal, A.; et al. Regulation of T-cell activation and migration by the kinase TBK1 during neuroinflammation. Nat. Commun. 2015, 6. [CrossRef] [PubMed]
12. Limbach, P.A.; Crain, P.F.; McCloskey, J.A. Summary: The modified nucleosides of RNA. Nucleic Acids Res. 1994, 22, 2183-2196. [CrossRef] [PubMed]
13. Marbaniang, C.N.; Vogel, J. Emerging roles of RNA modifications in bacteria. Curr. Opin. Microbiol. 2016, 30, 50-57. [CrossRef] [PubMed]
14. Machnicka, M.A.; Milanowska, K.; Osman Oglou, O.; Purta, E.; Kurkowska, M.; Olchowik, A.; Januszewski, W.; Kalinowski, S.; Dunin-Horkawicz, S.; Rother, K.M.; et al. Modomics: A database of RNA modification pathways-2013 update. Nucleic Acids Res. 2013, 41, D262-D267. [CrossRef] [PubMed]
15. Chan, C.T.; Chionh, Y.H.; Ho, C.H.; Lim, K.S.; Babu, I.R.; Ang, E.; Wenwei, L.; Alonso, S.; Dedon, P.C. Identification of N6,N6-dimethyladenosine in transfer RNA from Mycobacterium bovis Bacille Calmette-Guérin. Molecules 2011, 16, 5168-5181. [CrossRef] [PubMed]
16. Metodiev, M.D.; Lesko, N.; Park, C.B.; Cámara, Y.; Shi, Y.; Wibom, R.; Hultenby, K.; Gustafsson, C.M.; Larsson, N.G. Methylation of 12S rRNA is necessary for in vivo stability of the small subunit of the mammalian mitochondrial ribosome. Cell Metab. 2009, 9, 386-397. [CrossRef] [PubMed]
17. Helser, T.L.; Davies, J.E.; Dahlberg, J.E. Change in methylation of 16S ribosomal RNA associated with mutation to Kasugamycin resistance in Escherichia coli. Nature 1971, 233, 12-14. [CrossRef]
18. Poldermans, B.; Bakker, H.; van Knippenberg, P.H. Studies on the function of two adjacent N6,N6-dimethyladenosines near the 3' end of 16S ribosomal RNA of Escherichia coli. IV. The effect of the methylgroups on ribosomal subunit interaction. Nucleic Acids Res. 1980, 8, 143-151. [CrossRef] [PubMed]
19. Liu, J.; Yue, Y.; Han, D.;Wang, X.; Fu, Y.; Zhang, L.; Jia, G.; Yu, M.; Lu, Z.; Deng, X.; et al. A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-Adenosine methylation. Nat. Chem. Biol. 2014, 10, 93-95. [CrossRef] [PubMed]
20. Bokar, J.A.; Rath-Shambaugh, M.E.; Ludwiczak, R.; Narayan, P.; Rottman, F. Characterization and partial purification of mRNA N6-Adenosine methyltransferase from HeLa cell nuclei. Internal mRNA methylation requires a multisubunit complex. J. Biol. Chem. 1994, 269, 17697-17704. [PubMed]
21. Bergmann,W.; Feeney, R.J. Contributions to the study of marine products. XXXII. The nucleosides of sponges. I.1. J. Org. Chem. 1951, 16, 981-987. [CrossRef]
22. Tortora, G.; Ciardiello, F.; Pepe, S.; Tagliaferri, P.; Ruggiero, A.; Bianco, C.; Guarrasi, R.; Miki, K.; Bianco, A. Phase I clinical study with 8-chloro-cAMP and evaluation of immunological effects in cancer patients. Clin. Cancer Res. 1995, 1, 377-384. [PubMed]
23. Krett, N.L.; Davies, K.M.; Ayres, M.; Ma, C.; Nabhan, C.; Gandhi, V.; Rosen, S.T. 8-Amino-Adenosine is a potential therapeutic agent for multiple myeloma. Mol. Cancer Ther. 2004, 3, 1411-1420. [PubMed]
24. Stellrecht, C.M.; Vangapandu, H.V.; Le, X.-F.; Mao,W.; Shentu, S. ATP directed agent, 8-chloro-Adenosine, induces AMP activated protein kinase activity, leading to autophagic cell death in breast cancer cells. J. Hematol. Oncol. 2014, 7, 1-13. [CrossRef] [PubMed]
25. Kearney, A.Y.; Fan, Y.-H.; Giri, U.; Saigal, B.; Gandhi, V.; Heymach, J.V.; Zurita, A.J. 8-chloroadenosine sensitivity in renal cell carcinoma is associated with AMPK activation and mTOR pathway inhibition. PLoS ONE 2015, 10, e0135962. [CrossRef] [PubMed]
26. Dennison, J.B.; Shanmugam, M.; Ayres, M.L.; Qian, J.; Krett, N.L.; Medeiros, L.J.; Neelapu, S.S.; Rosen, S.T.; Gandhi, V. 8-Aminoadenosine inhibits Akt/mTOR and Erk signaling in mantle cell lymphoma. Blood 2010, 116, 5622-5630. [CrossRef] [PubMed]