title: mTOR: a pharmacologic target for autophagy regulation.
abstract: mTOR, a serine/threonine kinase, is a master regulator of cellular metabolism. mTOR regulates cell growth and proliferation in response to a wide range of cues, and its signaling pathway is deregulated in many human diseases. mTOR also plays a crucial role in regulating autophagy. This Review provides an overview of the mTOR signaling pathway, the mechanisms of mTOR in autophagy regulation, and the clinical implications of mTOR inhibitors in disease treatment.
authors: Young Chul
authors: YC
authors: Kim
authors: Kun-Liang
authors: KL
authors: Guan
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D006801:Humans; D008687:Metformin / Q000494:pharmacology; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D008687:Metformin; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
references: J Biol Chem. 2011 Nov 18;286(46):40002-12
references: 21949121
references: Science. 2011 Jun 17;332(6036):1429-33
references: 21617040
references: J Biol Chem. 2010 Jun 25;285(26):20109-16
references: 20427287
references: Genes Dev. 2004 Dec 1;18(23):2893-904
references: 15545625
references: Science. 2013 May 31;340(6136):1100-6
references: 23723238
references: Cell. 2012 Apr 13;149(2):274-93
references: 22500797
references: Cell. 2006 Oct 6;127(1):125-37
references: 16962653
references: Nat Cell Biol. 2013 Apr;15(4):406-16
references: 23524951
references: Cell Death Dis. 2014 Feb 27;5:e1088
references: 24577086
references: J Clin Invest. 2015 Jan;125(1):14-24
references: 25654546
references: J Cell Biol. 2000 Sep 18;150(6):1507-13
references: 10995454
references: Cell Res. 2014 Jan;24(1):42-57
references: 24343578
references: Mol Cell Biol. 2010 Feb;30(4):908-21
references: 19995915
references: J Biol Chem. 2009 May 1;284(18):12297-305
references: 19258318
references: Science. 2011 Jun 10;332(6035):1322-6
references: 21659605
references: Nat Cell Biol. 2008 Aug;10(8):935-45
references: 18604198
references: Mol Cell. 2003 Apr;11(4):895-904
references: 12718876
references: Cell. 2012 Apr 13;149(2):410-24
references: 22424946
references: Cell Death Dis. 2013 Nov 14;4:e917
references: 24232093
references: Am J Pathol. 1976 Jun;83(3):485-92
references: 937509
references: Mol Cell. 2008 Apr 25;30(2):214-26
references: 18439900
references: PLoS One. 2007 Nov 21;2(11):e1217
references: 18030348
references: Diabetes. 2011 Jun;60(6):1770-8
references: 21562078
references: Nat Cell Biol. 2011 Feb;13(2):132-41
references: 21258367
references: Nat Cell Biol. 2007 Mar;9(3):316-23
references: 17277771
references: J Biophys Biochem Cytol. 1957 May 25;3(3):349-62
references: 13438920
references: Nat Cell Biol. 2004 Nov;6(11):1122-8
references: 15467718
references: J Cell Biol. 2013 Feb 18;200(4):475-91
references: 23401004
references: Genes Dev. 2006 Oct 15;20(20):2820-32
references: 17043309
references: J Clin Invest. 2011 Apr;121(4):1231-41
references: 21490404
references: Cell. 2011 Mar 4;144(5):757-68
references: 21376236
references: Autophagy. 2013 Oct;9(10):1631-2
references: 23989658
references: Nat Cell Biol. 2002 Sep;4(9):658-65
references: 12172554
references: EMBO J. 2012 Mar 7;31(5):1095-108
references: 22343943
references: Mol Cell Biol. 2006 Jan;26(1):63-76
references: 16354680
references: J Biol Chem. 1998 Feb 13;273(7):3963-6
references: 9461583
references: Science. 2011 Nov 4;334(6056):678-83
references: 22053050
references: Curr Biol. 2003 Aug 5;13(15):1259-68
references: 12906785
references: Cell. 2011 Nov 11;147(4):728-41
references: 22078875
references: J Clin Invest. 2015 Jan;125(1):5-13
references: 25654545
references: Science. 2011 Jun 10;332(6035):1317-22
references: 21659604
references: Oncogene. 2010 Jul 1;29(26):3733-44
references: 20418915
references: Cancer Res. 2010 Jan 1;70(1):288-98
references: 20028854
references: Autophagy. 2012 Jun;8(6):903-14
references: 22576015
references: Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12574-8
references: 7809080
references: J Cell Biol. 2004 Jul 19;166(2):213-23
references: 15249583
references: Science. 2008 Jun 13;320(5882):1496-501
references: 18497260
references: Curr Biol. 2006 Sep 19;16(18):1865-70
references: 16919458
references: Cell. 2002 Jul 26;110(2):177-89
references: 12150926
references: Nat Cell Biol. 2003 Jun;5(6):566-71
references: 12766776
references: Cancer Res. 2011 Jul 1;71(13):4366-72
references: 21540236
references: Mol Cell. 2007 Mar 23;25(6):903-15
references: 17386266
references: Cell. 2002 Jul 26;110(2):163-75
references: 12150925
references: J Clin Invest. 2013 Mar;123(3):980-9
references: 23454761
references: Cell. 2014 Feb 13;156(4):771-85
references: 24529379
references: Proc Natl Acad Sci U S A. 2009 Jun 16;106(24):9902-7
references: 19497867
references: Proc Natl Acad Sci U S A. 2011 Jul 26;108(30):12455-60
references: 21746920
references: J Clin Invest. 2015 Jan;125(1):42-6
references: 25654549
references: Nature. 2010 Jun 17;465(7300):942-6
references: 20526321
references: Cell. 2013 Aug 15;154(4):859-74
references: 23953116
references: Nat Genet. 2004 Jun;36(6):585-95
references: 15146184
references: Cell. 1994 Jul 15;78(1):35-43
references: 7518356
references: Nat Rev Drug Discov. 2006 Aug;5(8):671-88
references: 16883305
references: Cell Metab. 2010 May 5;11(5):390-401
references: 20444419
references: Cell. 2010 Apr 16;141(2):290-303
references: 20381137
references: Nat Rev Drug Discov. 2011 Oct 31;10(11):868-80
references: 22037041
references: Cell Death Dis. 2011 Sep 01;2:e199
references: 21881601
references: Annu Rev Physiol. 1966;28:435-92
references: 5322983
references: Proc Natl Acad Sci U S A. 2008 Nov 11;105(45):17414-9
references: 18955708
references: Mol Cell Biol. 2011 Jul;31(14):2867-76
references: 21576371
references: FEBS Lett. 2008 Jan 9;582(1):81-9
references: 18022388
references: Nat Cell Biol. 2002 Sep;4(9):648-57
references: 12172553
references: Nat Commun. 2014 Jul 01;5:4241
references: 24980141
references: Mol Cell. 2013 Nov 21;52(4):495-505
references: 24095279
references: Hum Mol Genet. 2002 May 1;11(9):1107-17
references: 11978769
references: Cell Death Dis. 2012 Mar 01;3:e275
references: 22378068
references: Cell Metab. 2014 Mar 4;19(3):373-9
references: 24508508
references: Dev Cell. 2014 May 12;29(3):321-9
references: 24768164
references: Cancer Res. 2007 Nov 15;67(22):10804-12
references: 18006825
references: Nat Cell Biol. 2013 Oct;15(10):1186-96
references: 23955302
references: Cancer Res. 2007 Jul 15;67(14):6745-52
references: 17638885
references: Cell. 2003 Nov 26;115(5):577-90
references: 14651849
references: Am J Transplant. 2012 Jan;12(1):102-14
references: 21966953
references: Dev Cell. 2004 Aug;7(2):167-78
references: 15296714
references: Nat Rev Drug Discov. 2012 Sep;11(9):709-30
references: 22935804
references: Cell. 2013 Jan 17;152(1-2):290-303
references: 23332761
references: Genes Dev. 2003 Aug 1;17(15):1829-34
references: 12869586
references: Cell. 2009 May 29;137(5):873-86
references: 19446321
references: Biochem J. 2007 Aug 1;405(3):513-22
references: 17461779
references: Nature. 1977 Nov 10;270(5633):174-6
references: 927529
references: Cancer Res. 2005 Apr 15;65(8):3336-46
references: 15833867
references: N Engl J Med. 2013 Feb 14;368(7):651-62
references: 23406030
references: Nat Rev Mol Cell Biol. 2014 Mar;15(3):155-62
references: 24556838
references: FEBS Lett. 2010 Apr 2;584(7):1287-95
references: 20083114
references: Mol Biol Cell. 2009 Apr;20(7):1992-2003
references: 19225151
references: EMBO J. 2010 Dec 1;29(23):3939-51
references: 21045808
references: Nat Rev Mol Cell Biol. 2013 May;14(5):283-96
references: 23609508
references: Cancer Cell. 2009 Feb 3;15(2):148-59
references: 19185849
references: Proc Natl Acad Sci U S A. 2004 Sep 14;101(37):13489-94
references: 15342917
references: J Biol Chem. 2001 Mar 9;276(10):7246-57
references: 11073942
references: Science. 1991 Aug 23;253(5022):905-9
references: 1715094
references: J Cell Sci. 2013 Apr 15;126(Pt 8):1713-9
references: 23641065
references: Nature. 2004 Sep 9;431(7005):200-5
references: 15306821
references: Science. 2005 Feb 18;307(5712):1098-101
references: 15718470
references: Nat Rev Mol Cell Biol. 2013 Mar;14(3):133-9
references: 23361334
references: Mol Cell. 2002 Jul;10(1):151-62
references: 12150915
references: Trends Cell Biol. 2014 Jul;24(7):400-6
references: 24698685
references: Curr Biol. 2004 Jul 27;14(14):1296-302
references: 15268862
references: J Biol Chem. 1995 Jan 13;270(2):815-22
references: 7822316
references: Cell. 2012 Sep 14;150(6):1196-208
references: 22980980
references: Cell. 2005 Apr 22;121(2):179-93
references: 15851026
references: J Biol Chem. 2009 Mar 20;284(12):8023-32
references: 19150980
references: Genes Dev. 2008 Jan 15;22(2):239-51
references: 18198340
references: Mol Biol Cell. 2009 Apr;20(7):1981-91
references: 19211835
references: J Biol Chem. 2007 Jul 6;282(27):20036-44
references: 17510057
references: Sci Signal. 2009 Apr 21;2(67):pe24
references: 19383975
references: Nature. 1994 Jun 30;369(6483):756-8
references: 8008069
references: Autophagy. 2013 Dec;9(12):1983-95
references: 24013218
references: Nat Cell Biol. 2003 Jun;5(6):559-65
references: 12766775
references: Science. 2013 Jul 26;341(6144):1236566
references: 23888043