Disruption of the Rag-Ragulator Complex by c17orf59 Inhibits mTORC1

Cell Reports

Volumn 12, Issue 9, 2015, Pages 1445-1455

  Schweitzer, Lawrence D ^a,b,c   Comb, William C ^a,b,c   Bar Peled, Liron ^a,b,c   Sabatini, David M ^a,b,c  

^a WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH   (United States)

^b MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^c BROAD INSTITUTE OF MIT AND HARVARD   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; BINDING PROTEIN; C17ORF59 PROTEIN; GUANOSINE TRIPHOSPHATASE; INSULIN; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MULTIPROTEIN COMPLEX; RAG PROTEIN; RAGULATOR COMPLEX; UNCLASSIFIED DRUG; MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1; MONOMERIC GUANINE NUCLEOTIDE BINDING PROTEIN; PROTEIN BINDING; SIGNAL TRANSDUCING ADAPTOR PROTEIN; TARGET OF RAPAMYCIN KINASE;

ARTICLE; CELLULAR DISTRIBUTION; CONTROLLED STUDY; HUMAN; HUMAN CELL; IN VITRO STUDY; LYSOSOME; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION; GENETICS; HEK293 CELL LINE; HELA CELL LINE; METABOLISM;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; HEK293 CELLS; HELA CELLS; HUMANS; LYSOSOMES; MONOMERIC GTP-BINDING PROTEINS; MULTIPROTEIN COMPLEXES; PROTEIN BINDING; TOR SERINE-THREONINE KINASES;

EID: 84940789032     PISSN: None     EISSN: 22111247     Source Type: Journal    
DOI: 10.1016/j.celrep.2015.07.052     Document Type: Article

References (46)

1. Bar-Peled L., Schweitzer L.D., Zoncu R., Sabatini D.M. Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1. Cell 2012, 150:1196-1208.
2. Bar-Peled L., Chantranupong L., Cherniack A.D., Chen W.W., Ottina K.A., Grabiner B.C., Spear E.D., Carter S.L., Meyerson M., Sabatini D.M. A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1. Science 2013, 340:1100-1106.
3. Bartz F., Kern L., Erz D., Zhu M., Gilbert D., Meinhof T., Wirkner U., Erfle H., Muckenthaler M., Pepperkok R., Runz H. Identification of cholesterol-regulating genes by targeted RNAi screening. Cell Metab. 2009, 10:63-75.
4. Bonfils G., Jaquenoud M., Bontron S., Ostrowicz C., Ungermann C., De Virgilio C. Leucyl-tRNA synthetase controls TORC1 via the EGO complex. Mol. Cell 2012, 46:105-110.
5. Brohawn S.G., Partridge J.R., Whittle J.R., Schwartz T.U. The nuclear pore complex has entered the atomic age. Structure 2009, 17:1156-1168.
6. Chantranupong L., Wolfson R.L., Orozco J.M., Saxton R.A., Scaria S.M., Bar-Peled L., Spooner E., Isasa M., Gygi S.P., Sabatini D.M. The Sestrins interact with GATOR2 to negatively regulate the amino-acid-sensing pathway upstream of mTORC1. Cell Rep. 2014, 9:1-8.
7. Devos D., Dokudovskaya S., Alber F., Williams R., Chait B.T., Sali A., Rout M.P. Components of coated vesicles and nuclear pore complexes share a common molecular architecture. PLoS Biol. 2004, 2:e380.
8. Efeyan A., Zoncu R., Chang S., Gumper I., Snitkin H., Wolfson R.L., Kirak O., Sabatini D.D., Sabatini D.M. Regulation of mTORC1 by the Rag GTPases is necessary for neonatal autophagy and survival. Nature 2013, 493:679-683.
9. Feldman M.E., Shokat K.M. New inhibitors of the PI3K-Akt-mTOR pathway: insights into mTOR signaling from a new generation of Tor Kinase Domain Inhibitors (TORKinibs). Curr. Top. Microbiol. Immunol. 2010, 347:241-262.
10. Feldman M.E., Apsel B., Uotila A., Loewith R., Knight Z.A., Ruggero D., Shokat K.M. Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2. PLoS Biol. 2009, 7:e38.
11. Garami A., Zwartkruis F.J., Nobukuni T., Joaquin M., Roccio M., Stocker H., Kozma S.C., Hafen E., Bos J.L., Thomas G. Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2. Mol. Cell 2003, 11:1457-1466.
12. Gomes A.P., Blenis J. A nexus for cellular homeostasis: the interplay between metabolic and signal transduction pathways. Curr. Opin. Biotechnol. 2015, 34C:110-117.
13. Gürkan C., Stagg S.M., Lapointe P., Balch W.E. The COPII cage: unifying principles of vesicle coat assembly. Nat. Rev. Mol. Cell Biol. 2006, 7:727-738.
14. Han J.M., Jeong S.J., Park M.C., Kim G., Kwon N.H., Kim H.K., Ha S.H., Ryu S.H., Kim S. Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway. Cell 2012, 149:410-424.
15. Hara K., Yonezawa K., Weng Q.P., Kozlowski M.T., Belham C., Avruch J. Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism. J. Biol. Chem. 1998, 273:14484-14494.
16. Inoki K., Li Y., Zhu T., Wu J., Guan K.L. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat. Cell Biol. 2002, 4:648-657.
17. Inoki K., Li Y., Xu T., Guan K.L. Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes Dev. 2003, 17:1829-1834.
18. Jewell J.L., Guan K.L. Nutrient signaling to mTOR and cell growth. Trends Biochem. Sci. 2013, 38:233-242.
19. Kim E., Goraksha-Hicks P., Li L., Neufeld T.P., Guan K.L. Regulation of TORC1 by Rag GTPases in nutrient response. Nat. Cell Biol. 2008, 10:935-945.
20. Kim Y.M., Stone M., Hwang T.H., Kim Y.G., Dunlevy J.R., Griffin T.J., Kim D.H. SH3BP4 is a negative regulator of amino acid-Rag GTPase-mTORC1 signaling. Mol. Cell 2012, 46:833-846.
21. Laplante M., Sabatini D.M. mTOR signaling in growth control and disease. Cell 2012, 149:274-293.
22. Long X., Lin Y., Ortiz-Vega S., Yonezawa K., Avruch J. Rheb binds and regulates the mTOR kinase. Curr. Biol. 2005, 15:702-713.
23. Long X., Ortiz-Vega S., Lin Y., Avruch J. Rheb binding to mammalian target of rapamycin (mTOR) is regulated by amino acid sufficiency. J. Biol. Chem. 2005, 280:23433-23436.
24. Lynch C.J., Fox H.L., Vary T.C., Jefferson L.S., Kimball S.R. Regulation of amino acid-sensitive TOR signaling by leucine analogues in adipocytes. J. Cell. Biochem. 2000, 77:234-251.
25. Manning B.D., Tee A.R., Logsdon M.N., Blenis J., Cantley L.C. Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway. Mol. Cell 2002, 10:151-162.
26. Menon S., Dibble C.C., Talbott G., Hoxhaj G., Valvezan A.J., Takahashi H., Cantley L.C., Manning B.D. Spatial control of the TSC complex integrates insulin and nutrient regulation of mTORC1 at the lysosome. Cell 2014, 156:771-785.
27. Nada S., Hondo A., Kasai A., Koike M., Saito K., Uchiyama Y., Okada M. The novel lipid raft adaptor p18 controls endosome dynamics by anchoring the MEK-ERK pathway to late endosomes. EMBO J. 2009, 28:477-489.
28. Nobukuni T., Joaquin M., Roccio M., Dann S.G., Kim S.Y., Gulati P., Byfield M.P., Backer J.M., Natt F., Bos J.L., et al. Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase. Proc. Natl. Acad. Sci. USA 2005, 102:14238-14243.
29. Panchaud N., Péli-Gulli M.P., De Virgilio C. Amino acid deprivation inhibits TORC1 through a GTPase-activating protein complex for the Rag family GTPase Gtr1. Sci. Signal. 2013, 6:ra42.
30. Parmigiani A., Nourbakhsh A., Ding B., Wang W., Kim Y.C., Akopiants K., Guan K.L., Karin M., Budanov A.V. Sestrins inhibit mTORC1 kinase activation through the GATOR complex. Cell Rep. 2014, 9:1281-1291.
31. Peng M., Yin N., Li M.O. Sestrins function as guanine nucleotide dissociation inhibitors for Rag GTPases to control mTORC1 signaling. Cell 2014, 159:122-133.
32. Pu J., Schindler C., Jia R., Jarnik M., Backlund P., Bonifacino J.S. BORC, a multisubunit complex that regulates lysosome positioning. Dev. Cell. 2015, 33:176-188.
33. Sancak Y., Peterson T.R., Shaul Y.D., Lindquist R.A., Thoreen C.C., Bar-Peled L., Sabatini D.M. The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science 2008, 320:1496-1501.
34. 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.
35. Sarbassov D.D., Ali S.M., Sengupta S., Sheen J.H., Hsu P.P., Bagley A.F., Markhard A.L., Sabatini D.M. Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol. Cell 2006, 22:159-168.
36. Shimobayashi M., Hall M.N. Making new contacts: the mTOR network in metabolism and signalling crosstalk. Nat. Rev. Mol. Cell Biol. 2014, 15:155-162.
37. Smith E.M., Finn S.G., Tee A.R., Browne G.J., Proud C.G. The tuberous sclerosis protein TSC2 is not required for the regulation of the mammalian target of rapamycin by amino acids and certain cellular stresses. J. Biol. Chem. 2005, 280:18717-18727.
38. Takahashi Y., Nada S., Mori S., Soma-Nagae T., Oneyama C., Okada M. The late endosome/lysosome-anchored p18-mTORC1 pathway controls terminal maturation of lysosomes. Biochem. Biophys. Res. Commun. 2012, 417:1151-1157.
39. Tee A.R., Manning B.D., Roux P.P., Cantley L.C., Blenis J. Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb. Curr. Biol. 2003, 13:1259-1268.
40. Teis D., Taub N., Kurzbauer R., Hilber D., de Araujo M.E., Erlacher M., Offterdinger M., Villunger A., Geley S., Bohn G., et al. p14-MP1-MEK1 signaling regulates endosomal traffic and cellular proliferation during tissue homeostasis. J. Cell Biol. 2006, 175:861-868.
41. Thoreen C.C., Kang S.A., Chang J.W., Liu Q., Zhang J., Gao Y., Reichling L.J., Sim T., Sabatini D.M., Gray N.S. An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J. Biol. Chem. 2009, 284:8023-8032.
42. Vogel G.F., Ebner H.L., de Araujo M.E., Schmiedinger T., Eiter O., Pircher H., Gutleben K., Witting B., Teis D., Huber L.A., Hess M.W. Ultrastructural Morphometry Points to a New Role for LAMTOR2 in Regulating the Endo/Lysosomal System. Traffic 2015, 16:617-634.
43. Wunderlich W., Fialka I., Teis D., Alpi A., Pfeifer A., Parton R.G., Lottspeich F., Huber L.A. A novel 14-kilodalton protein interacts with the mitogen-activated protein kinase scaffold mp1 on a late endosomal/lysosomal compartment. J. Cell Biol. 2001, 152:765-776.
44. Zhang Y., Gao X., Saucedo L.J., Ru B., Edgar B.A., Pan D. Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins. Nat. Cell Biol. 2003, 5:578-581.
45. Zhang Y., Nicholatos J., Dreier J.R., Ricoult S.J., Widenmaier S.B., Hotamisligil G.S., Kwiatkowski D.J., Manning B.D. Coordinated regulation of protein synthesis and degradation by mTORC1. Nature 2014, 513:440-443.
46. Zoncu R., Bar-Peled L., Efeyan A., Wang S., Sancak Y., Sabatini D.M. mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase. Science 2011, 334:678-683.