Lysosomal mTORC2/PHLPP1/Akt Regulate Chaperone-Mediated Autophagy

Molecular Cell

Volumn 59, Issue 2, 2015, Pages 270-284

  Arias, Esperanza ^a   Koga, Hiroshi ^a   Diaz, Antonio ^a   Mocholi, Enric ^a   Patel, Bindi ^a   Cuervo, Ana María ^a  

^a ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; PHLPP1 PROTEIN; PHOSPHATASE; PROTEIN KINASE B; UNCLASSIFIED DRUG; CHAPERONE; MULTIPROTEIN COMPLEX; NUCLEAR PROTEIN; PHLPP PROTEIN, MOUSE; PHLPP1 PROTEIN, HUMAN; PHLPP1 PROTEIN, RAT; PHOSPHOPROTEIN PHOSPHATASE; TARGET OF RAPAMYCIN KINASE; TOR COMPLEX 2;

ADULT; AGING; ANIMAL CELL; ARTICLE; CHAPERONE-MEDIATED AUTOPHAGY; CONTROLLED STUDY; DYNAMICS; HUMAN; HUMAN CELL; LYSOSOME; LYSOSOME MEMBRANE; MALE; MOUSE; NONHUMAN; RAT; 3T3 CELL LINE; ANIMAL; ANTAGONISTS AND INHIBITORS; AUTOPHAGY; C57BL MOUSE; GENE SILENCING; GENETICS; LIVER; METABOLISM; PHYSIOLOGY; PROTEIN DEGRADATION; TUMOR CELL LINE; WISTAR RAT;

ANIMALS; AUTOPHAGY; CELL LINE, TUMOR; GENE KNOCKDOWN TECHNIQUES; HUMANS; LIVER; LYSOSOMES; MALE; MICE; MICE, INBRED C57BL; MOLECULAR CHAPERONES; MULTIPROTEIN COMPLEXES; NIH 3T3 CELLS; NUCLEAR PROTEINS; PHOSPHOPROTEIN PHOSPHATASES; PROTEOLYSIS; PROTO-ONCOGENE PROTEINS C-AKT; RATS; RATS, WISTAR; TOR SERINE-THREONINE KINASES;

EID: 84937520970     PISSN: 10972765     EISSN: 10974164     Source Type: Journal    
DOI: 10.1016/j.molcel.2015.05.030     Document Type: Article

References (34)

1. Agarraberes F.A., Terlecky S.R., Dice J.F. An intralysosomal hsp70 is required for a selective pathway of lysosomal protein degradation. J.Cell Biol. 1997, 137:825-834.
2. Bandyopadhyay U., Kaushik S., Varticovski L., Cuervo A.M. The chaperone-mediated autophagy receptor organizes in dynamic protein complexes at the lysosomal membrane. Mol. Cell. Biol. 2008, 28:5747-5763.
3. Bandyopadhyay U., Sridhar S., Kaushik S., Kiffin R., Cuervo A.M. Identification of regulators of chaperone-mediated autophagy. Mol. Cell 2010, 39:535-547.
4. Benjamin D., Colombi M., Moroni C., Hall M.N. Rapamycin passes the torch: a new generation of mTOR inhibitors. Nat. Rev. Drug Discov. 2011, 10:868-880.
5. Chiang H.L., Terlecky S.R., Plant C.P., Dice J.F. A role for a 70-kilodalton heat shock protein in lysosomal degradation of intracellular proteins. Science 1989, 246:382-385.
6. Copp J., Manning G., Hunter T. TORC-specific phosphorylation of mammalian target of rapamycin (mTOR): phospho-Ser2481 is a marker for intact mTOR signaling complex 2. Cancer Res. 2009, 69:1821-1827.
7. Cuervo A.M., Dice J.F. A receptor for the selective uptake and degradation of proteins by lysosomes. Science 1996, 273:501-503.
8. Cuervo A.M., Knecht E., Terlecky S.R., Dice J.F. Activation of a selective pathway of lysosomal proteolysis in rat liver by prolonged starvation. Am. J. Physiol. 1995, 269:C1200-C1208.
9. Cuervo A.M., Dice J.F., Knecht E. A population of rat liver lysosomes responsible for the selective uptake and degradation of cytosolic proteins. J.Biol. Chem. 1997, 272:5606-5615.
10. Durán R.V., Hall M.N. Regulation of TOR by small GTPases. EMBO Rep. 2012, 13:121-128.
11. Gao T., Furnari F., Newton A.C. PHLPP: a phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumor growth. Mol. Cell 2005, 18:13-24.
12. Gao T., Brognard J., Newton A.C. The phosphatase PHLPP controls the cellular levels of protein kinase C. J.Biol. Chem. 2008, 283:6300-6311.
13. Hubbi M.E., Hu H., Kshitiz, Ahmed I., Levchenko A., Semenza G.L. Chaperone-mediated autophagy targets hypoxia-inducible factor-1α (HIF-1α) for lysosomal degradation. J.Biol. Chem. 2013, 288:10703-10714.
14. Kaushik S., Cuervo A.M. Methods to monitor chaperone-mediated autophagy. Methods Enzymol. 2009, 452:297-324.
15. Kaushik S., Cuervo A.M. Chaperone-mediated autophagy: aunique way to enter the lysosome world. Trends Cell Biol. 2012, 22:407-417.
16. Kaushik S., Massey A., Mizushima N., Cuervo A.M. Constitutive activation of chaperone-mediated autophagy in cells with impaired macroautophagy. Mol. Biol. Cell 2008, 19:2179-2192.
17. Kiffin R., Christian C., Knecht E., Cuervo A.M. Activation of chaperone-mediated autophagy during oxidative stress. Mol. Biol. Cell 2004, 15:4829-4840.
18. Koga H., Martinez-Vicente M., Macian F., Verkhusha V.V., Cuervo A.M. A photoconvertible fluorescent reporter to track chaperone-mediated autophagy. Nat. Commun. 2011, 2:386.
19. Kon M., Kiffin R., Koga H., Chapochnick J., Macian F., Varticovski L., Cuervo A.M. Chaperone-mediated autophagy is required for tumor growth. Sci. Transl Med. 2011, 3:109ra117.
20. Korolchuk V.I., Saiki S., Lichtenberg M., Siddiqi F.H., Roberts E.A., Imarisio S., Jahreiss L., Sarkar S., Futter M., Menzies F.M., et al. Lysosomal positioning coordinates cellular nutrient responses. Nat. Cell Biol. 2011, 13:453-460.
21. Kriel A., Bittner A.N., Kim S.H., Liu K., Tehranchi A.K., Zou W.Y., Rendon S., Chen R., Tu B.P., Wang J.D. Direct regulation of GTP homeostasis by (p)ppGpp: a critical component of viability and stress resistance. Mol. Cell 2012, 48:231-241.
22. Kroemer G., Mariño G., Levine B. Autophagy and the integrated stress response. Mol. Cell 2010, 40:280-293.
23. Massey A.C., Kaushik S., Sovak G., Kiffin R., Cuervo A.M. Consequences of the selective blockage of chaperone-mediated autophagy. Proc. Natl. Acad. Sci. USA 2006, 103:5805-5810.
24. Mizushima N., Levine B., Cuervo A.M., Klionsky D.J. Autophagy fights disease through cellular self-digestion. Nature 2008, 451:1069-1075.
25. Obenauer J.C., Cantley L.C., Yaffe M.B. Scansite 2.0: Proteome-wide prediction of cell signaling interactions using short sequence motifs. Nucleic Acids Res. 2003, 31:3635-3641.
26. Park C., Suh Y., Cuervo A.M. Regulated degradation of Chk1 by chaperone-mediated autophagy in response to DNA damage. Nat. Commun. 2015, 6:6823.
27. Renna M., Bento C.F., Fleming A., Menzies F.M., Siddiqi F.H., Ravikumar B., Puri C., Garcia-Arencibia M., Sadiq O., Corrochano S., et al. IGF-1 receptor antagonism inhibits autophagy. Hum. Mol. Genet. 2013, 22:4528-4544.
28. Saci A., Cantley L.C., Carpenter C.L. Rac1 regulates the activity of mTORC1 and mTORC2 and controls cellular size. Mol. Cell 2011, 42:50-61.
29. Sancak Y., Bar-Peled L., Zoncu R., Markhard A.L., Nada S., Sabatini D.M. Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell 2010, 141:290-303.
30. Sarbassov D.D., Guertin D.A., Ali S.M., Sabatini D.M. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 2005, 307:1098-1101.
31. Schneider J.L., Suh Y., Cuervo A.M. Deficient chaperone-mediated autophagy in liver leads to metabolic dysregulation. Cell Metab. 2014, 20:417-432.
32. Sierecki E., Sinko W., McCammon J.A., Newton A.C. Discovery of small molecule inhibitors of the PH domain leucine-rich repeat protein phosphatase (PHLPP) by chemical and virtual screening. J.Med. Chem. 2010, 53:6899-6911.
33. Storrie B., Madden E.A. Isolation of subcellular organelles. Methods Enzymol. 1990, 182:203-225.
34. Wang R.C., Wei Y., An Z., Zou Z., Xiao G., Bhagat G., White M., Reichelt J., Levine B. Akt-mediated regulation of autophagy and tumorigenesis through Beclin 1 phosphorylation. Science 2012, 338:956-959.