Pharmaceutical screen identifies novel target processes for activation of autophagy with a broad translational potential

Nature Communications

Volumn 6, Issue , 2015, Pages

  Chauhan, Santosh ^a   Ahmed, Zahra ^b   Bradfute, Steven B ^a   Arko Mensah, John ^a   Mandell, Michael A ^a   Won Choi, Seong ^a   Kimura, Tomonori ^a   Blanchet, Fabien ^b   Waller, Anna ^a   Mudd, Michal H ^a   Jiang, Shanya ^a   Sklar, Larry ^a   Timmins, Graham S ^c   Maphis, Nicole ^a   Bhaskar, Kiran ^a   Piguet, Vincent ^b   Deretic, Vojo ^a,d  

^a UNIVERSITY OF NEW MEXICO SCHOOL OF MEDICINE   (United States)

^b CARDIFF UNIVERSITY   (United Kingdom)

^c UNIVERSITY OF NEW MEXICO   (United States)

^d INSTITUTE OF LIFE SCIENCES   (India)

Author keywords

[No Author keywords available]

Indexed keywords

DISEASE TREATMENT; DRUG; HOMEOSTASIS; HUMAN IMMUNODEFICIENCY VIRUS; PROTEIN;

BASIC HELIX LOOP HELIX LEUCINE ZIPPER TRANSCRIPTION FACTOR; FLUBENDAZOLE; MEBENDAZOLE; MOLECULAR LIBRARY; TFEB PROTEIN, HUMAN;

ACETYLATION; ALZHEIMER DISEASE; ANALOGS AND DERIVATIVES; AUTOPHAGY; DRUG EFFECTS; HUMAN; LYSOSOME; METABOLISM; MICROTUBULE; MOLECULAR LIBRARY; PATHOPHYSIOLOGY; PHARMACOLOGY; PRECLINICAL STUDY;

ACETYLATION; ALZHEIMER DISEASE; AUTOPHAGY; BASIC HELIX-LOOP-HELIX LEUCINE ZIPPER TRANSCRIPTION FACTORS; DRUG EVALUATION, PRECLINICAL; HUMANS; LYSOSOMES; MEBENDAZOLE; MICROTUBULES; SMALL MOLECULE LIBRARIES;

EID: 84946043481     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms9620     Document Type: Article

References (70)

1. Mizushima, N., Yoshimori, T. & Ohsumi, Y. The role of Atg proteins in autophagosome formation. Annu. Rev. Cell Dev. Biol. 27, 107-132 (2011
2. Birgisdottir, A. B., Lamark, T. & Johansen, T. The LIR motif-crucial for selective autophagy. J. Cell Sci. 126, 3237-3247 (2013
3. Kroemer, G. Autophagy: a druggable process that is deregulated in aging and human disease. J. Clin. Invest. 125, 1-4 (2015
4. Deretic, V. et al. Immunologic manifestations of autophagy. J. Clin. Invest. 125, 75-84 (2015
5. Rabinowitz, J. D. & White, E. Autophagy and metabolism. Science 330, 1344-1348 (2010
6. Settembre, C. & Ballabio, A. Lysosome: regulator of lipid degradation pathways. Trends Cell Biol. 24, 743-750 (2014
7. White, E. The role for autophagy in cancer. J. Clin. Invest. 125, 42-46 (2015
8. Frake, R. A., Ricketts, T., Menzies, F. M. & Rubinsztein, D. C. Autophagy and neurodegeneration. J. Clin. Invest. 125, 65-74 (2015
9. Rubinsztein, D. C., Marino, G. & Kroemer, G. Autophagy and aging. Cell 146, 682-695 (2011
10. Rubinsztein, D. C., Codogno, P. & Levine, B. Autophagy modulation as a potential therapeutic target for diverse diseases. Nat. Rev. Drug Discov. 11, 709-730 (2012
11. Klionsky, D. J. & Thorburn, A. Clinical research and Autophagy. Autophagy 10, 1357-1358 (2014
12. Shoji-Kawata, S. et al. Identification of a candidate therapeutic autophagyinducing peptide. Nature 494, 201-206 (2013
13. Su, M. et al. Targeting gamma-herpesvirus 68 Bcl-2-mediated down-regulation of autophagy. J. Biol. Chem. 289, 8029-8040 (2014
14. Vakifahmetoglu-Norberg, H., Xia, H.-G. & Yuan, J. Pharmacologic agents targeting autophagy. J. Clin. Invest. 125, 5-13 (2015
15. Levine, B., Packer, M. & Codogno, P. Development of autophagy inducers in clinical medicine. J. Clin. Invest. 125, 14-24 (2015
16. Kabeya, Y. et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 19, 5720-5728 (2000
17. Klionsky, D. J. et al. Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy 4, 151-175 (2008
18. Kimura, S., Noda, T. & Yoshimori, T. Dissection of the autophagosome maturation process by a novel reporter protein, tandem fluorescent-tagged LC3. Autophagy 3, 452-460 (2007
19. Mizushima, N., Yoshimori, T. & Levine, B. Methods in mammalian autophagy research. Cell 140, 313-326 (2010
20. Larsen, K. B. et al. A reporter cell system to monitor autophagy based on p62/SQSTM1. Autophagy 6, 784-793 (2010
21. Spagnuolo, P. A. et al. The antihelmintic flubendazole inhibits microtubule function through a mechanism distinct from Vinca alkaloids and displays preclinical activity in leukemia and myeloma. Blood 115, 4824-4833 (2010
22. Janke, C. & Bulinski, J. C. Post-translational regulation of the microtubule cytoskeleton: mechanisms and functions. Nat. Rev. Mol. Cell Biol. 12, 773-786 (2011
23. Szyk, A. et al. Molecular basis for age-dependent microtubule acetylation by tubulin acetyltransferase. Cell 157, 1405-1415 (2014
24. Zilberman, Y. et al. Regulation of microtubule dynamics by inhibition of the tubulin deacetylase HDAC6. J. Cell Sci. 122, 3531-3541 (2009
25. Akella, J. S. et al. MEC-17 is an alpha-tubulin acetyltransferase. Nature 467, 218-222 (2010
26. Zoncu, R. et al. mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase. Science 334, 678-683 (2011
27. Sancak, Y. et al. Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell 141, 290-303 (2010
28. Groth-Pedersen, L., Ostenfeld, M. S., Hoyer-Hansen, M., Nylandsted, J. & Jaattela, M. Vincristine induces dramatic lysosomal changes and sensitizes cancer cells to lysosome-destabilizing siramesine. Cancer Res. 67, 2217-2225 (2007
29. Jo, H., Loison, F. & Luo, H. R. Microtubule dynamics regulates Akt signaling via dynactin p150. Cell. Signal. 26, 1707-1716 (2014
30. Sardiello, M. et al. A gene network regulating lysosomal biogenesis and function. Science 325, 473-477 (2009
31. Pena-Llopis, S. et al. Regulation of TFEB and V-ATPases by mTORC1. EMBO J 30, 3242-3258 (2011
32. Settembre, C. et al. A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB. EMBO J. 31, 1095-1108 (2012
33. Settembre, C. et al. TFEB links autophagy to lysosomal biogenesis. Science 332, 1429-1433 (2011
34. Perera, R. M. et al. Transcriptional control of autophagy-lysosome function drives pancreatic cancer metabolism. Nature 524, 361-365 (2015
35. Lippincott-Schwartz, J. et al. Microtubule-dependent retrograde transport of proteins into the ER in the presence of brefeldin A suggests an ER recycling pathway. Cell 60, 821-836 (1990
36. Geeraert, C. et al. Starvation-induced hyperacetylation of tubulin is required for the stimulation of autophagy by nutrient deprivation. J. Biol. Chem. 285, 24184-24194 (2010
37. Mackeh, R., Perdiz, D., Lorin, S., Codogno, P. & Pous, C. Autophagy and microtubules-new story, old players. J. Cell Sci. 126, 1071-1080 (2013
38. Wei, Y., Pattingre, S., Sinha, S., Bassik, M. & Levine, B. JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Mol. Cell 30, 678-688 (2008
39. Mackeh, R. et al. Reactive oxygen species, AMP-Activated protein kinase, and the transcription cofactor p300 regulate alpha-tubulin acetyltransferase-1 (alphaTAT-1/MEC-17)-dependent microtubule hyperacetylation during cell stress. J. Biol. Chem. 289, 11816-11828 (2014
40. Kochl, R., Hu, X. W., Chan, E. Y. & Tooze, S. A. Microtubules facilitate autophagosome formation and fusion of autophagosomes with endosomes. Traffic. 7, 129-145 (2006
41. Xie, R., Nguyen, S., McKeehan, W. L. & Liu, L. Acetylated microtubules are required for fusion of autophagosomes with lysosomes. BMC Cell Biol. 11, 89 (2010
42. Kyei, G. B. et al. Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yields in macrophages. J. Cell Biol. 186, 255-268 (2009
43. Blanchet, F. P. et al. Human immunodeficiency virus-1 inhibition of immunoamphisomes in dendritic cells impairs early innate and adaptive immune responses. Immunity 32, 654-669 (2010
44. Campbell, G. & Spector, S. Hormonally active vitamin D3 (1,25-dihydroxycholecalciferol) triggers autophagy in human macrophages that inhibits HIV-1 infection. J. Biol. Chem. 268, 18890-18902 (2011
45. Wu, L. & KewalRamani, V. N. Dendritic-cell interactions with HIV: infection and viral dissemination. Nat. Rev. Immunol. 6, 859-868 (2006
46. Piguet, V. & Steinman, R. M. The interaction of HIV with dendritic cells: outcomes and pathways. Trends Immunol. 28, 503-510 (2007
47. Puryear, W. B. & Gummuluru, S. Role of glycosphingolipids in dendritic cellmediated HIV-1 trans-infection. Adv. Exp. Med. Biol. 762, 131-153 (2013
48. Miller, E. & Bhardwaj, N. Dendritic cell dysregulation during HIV-1 infection. Immunol. Rev. 254, 170-189 (2013
49. Thoreen, C. C. et al. An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J. Biol. Chem. 284, 8023-8032 (2009
50. Consortium. Genome-wide association study of 14 000 cases of seven common diseases and 3,000 shared controls. Nature 447, 661-678 (2007
51. Murthy, A. et al. A Crohn's disease variant in Atg16l1 enhances its degradation by caspase 3. Nature 506, 456-462 (2014
52. McCarroll, S. A. et al. Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn's disease. Nat. Genet. 40, 1107-1112 (2008
53. Intemann, C. D. et al. Autophagy gene variant IRGM-261 T contributes to protection from tuberculosis caused by Mycobacterium tuberculosis but not by M. africanum strains. PLoS. Pathog. 5, e1000577 (2009
54. Lapaquette, P., Glasser, A. L., Huett, A., Xavier, R. J. & Darfeuille-Michaud, A. Crohn's disease-Associated adherent-invasive E. coli are selectively favoured by impaired autophagy to replicate intracellularly. Cell. Microbiol. 12, 99-113 (2009
55. Moreau, K. et al. PICALM modulates autophagy activity and tau accumulation. Nat. Commun. 5, 4998 (2014
56. Polito, V. A. et al. Selective clearance of aberrant tau proteins and rescue of neurotoxicity by transcription factor EB. EMBO Mol. Med. 6, 1142-1160 (2014
57. Bhaskar, K. et al. Regulation of tau pathology by the microglial fractalkine receptor. Neuron 68, 19-31 (2010
58. Sarkar, S. et al. Small molecules enhance autophagy and reduce toxicity in Huntington's disease models. Nat. Chem. Biol. 3, 331-338 (2007
59. Williams, A. et al. Novel targets for Huntington's disease in an mTORindependent autophagy pathway. Nat. Chem. Biol. 4, 295-305 (2008
60. Zhang, L. et al. Small molecule regulators of autophagy identified by an imagebased high-throughput screen. Proc. Natl Acad. Sci. USA 104, 19023-19028 (2007
61. Shaw, S. Y. et al. Selective modulation of autophagy, innate immunity, and adaptive immunity by small molecules. ACS Chem. Biol. 8, 2724-2733 (2013
62. Sun, T. et al. Acetylation of Beclin 1 inhibits autophagosome maturation and promotes tumour growth. Nat. Commun. 6, 7215 (2015
63. Huang, R. et al. Deacetylation of nuclear LC3 drives autophagy initiation under starvation. Mol. Cell 57, 456-466 (2015
64. Lee, M. J., Lee, J. H. & Rubinsztein, D. C. Tau degradation: the ubiquitinproteasome system versus the autophagy-lysosome system. Prog. Neurobiol. 105, 49-59 (2013
65. Lonskaya, I., Hebron, M. L., Desforges, N. M., Franjie, A. & Moussa, C. E. Tyrosine kinase inhibition increases functional parkin-Beclin-1 interaction and enhances amyloid clearance and cognitive performance. EMBO Mol. Med. 5, 1247-1262 (2013
66. Bendikov-Bar, I., Maor, G., Filocamo, M. & Horowitz, M. Ambroxol as a pharmacological chaperone for mutant glucocerebrosidase. Blood Cells Mol. Dis. 50, 141-145 (2013
67. McNeill, A. et al. Ambroxol improves lysosomal biochemistry in glucocerebrosidase mutation-linked Parkinson disease cells. Brain 137, 1481-1495 (2014
68. Lassegue, A. et al. Treatment of human alveolar echinococcosis with flubendazole. Clinical, morphological and immunological study. Gastroenterol. Clin. Biol. 8, 314-320 (1984
69. Arrighi, J. F. et al. DC-SIGN-mediated infectious synapse formation enhances X4 HIV-1 transmission from dendritic cells to T cells. J. Exp. Med. 200, 1279-1288 (2004
70. Eidenmuller, J. et al. Phosphorylation-mimicking glutamate clusters in the proline-rich region are sufficient to simulate the functional deficiencies of hyperphosphorylated tau protein. Biochem. J. 357, 759-767 (2001