I[gt@W[Ǝ

<strong>R rE떾</strong>
iVww@㎕w qwj
emailF<a href="mailto:komatsu-ms@med.niigata-u.ac.jp">떾</a>
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̈Zr[, <strong>3</strong>, e006 (2014)@<a href="http://dx.doi.org/10.7875/leading.author.3.e006">DOI: 10.7875/leading.author.3.e006</a>
Shun Kageyama & Masaaki Komatsu: <strong>Autophagy and disease states.</strong>

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<h2>v </h2>
@I[gt@W[֘A`q肳ĈȗC܂܂ȃfɂăI[gt@W[֘A`q̉ϓoCI[gt@W[̐@\CƂɁCA~m_v[̈ێזE̐VӂƂĂ̋@\mɂȂD܂C܂܂ȑɓٓIȃI[gt@W[֘A`q̉σ}EXCϐ^pNĈُȃIKl̒~ςƂȂ_oϐC̏QCȂǏdĂȎ悷邱Ƃ炩ɂȂCI[gt@W[ɂזEی̍pIɂȂDɁCזEɐN׋ۂُȃIKlCƂɕϐ~gRhÃI[gt@W[ɂIIȏ@\炩ɂC̕aԐIȖ͕G𑝂ĂDĂŋ߁CqgɂĂI[gt@W[֘A`q̕ψق_oϐ≊ǐЂNƂCI[gt@W[ُ̈킪qg̎ɂڂɊ֗^邱ƂD̃r[ł̓I[gt@W[TƂƂɁCI[gt@W[֘A`q̕ψقɂN`CI[gt@W[ُ̈킪GɊ֗^邪Ƃ肠D

<h2>͂߂</h2>
@I[gt@W[̓\\[ɂčזE̐𕪉@\łDI[gt@W[ɂ̓~NI[gt@W[CVyݐI[gt@W[C}NI[gt@W[3̌oHD̂ȂŁC}NI[gt@W[̉͂ƂiłCɁgI[gt@W[hƕ\Lꍇɂ̓}NI[gt@W[ƂC̃r[ɂĂɂDI[gt@W[͍זEɏouזE̐͂݃I[gt@S\[`ߒƁCI[gt@S\[\\[ƗZזE̐𕪉ߒȂDÉC~gRhACSẂCזECɂ́CTCNOGh\[ɗR鑽ʂȖI[gt@S\[̌`Ɋ^ĂČ`e̕܂ł́CI[gt@W[֘A`qiautophagy-related geneF<em>ATG</em>jɃR[hAtg^pNɂ茵ɐ䂳ĂD
@I[gt@S\[̌`ɓRAAtg^pŃCȉ6̋@\PʂɕނD1jULK1Li[[́iULK1CULK2CAtg13CFIP200CAtg101jC2jNXIIIzXt@`WCmVg[3-Li[[iPI3Li[[j́iVps34CVps15CBeclin 1CAtg14(L)/BarkorjC3jzXt@`WCmVg[-1,4,5-gX_iPI3Pj^pNiAtg2CWIPI1`WIPI4jC4j^pNiAtg9L1jC5jAtg12LniAtg12CAtg7CAtg10CAtg5CAtg16L1CAtg16L2jC6jLC3LniLC3A`LC3CCGABARAPCGABARAPL1CGABARAPL2CAtg4A`Atg4DCAtg7CAtg3jDRAAtg^pN̋@\PʂAIIɍ쓮邱ƂɂI[gt@S\[͌`<a href="#R1"><sup>1)</sup></a>i<a href="#F1">}1</a>jD

<a name="F1"></a><div id="fig1-caption-text" style="display: none;"><strong>}1@I[gt@S\[̌`ɂAtg^pN</strong>
I[gt@S\[̓RAAtg^pN6̋@\PʂIAIɍp邱Ƃɂ`DCXԂ邢͒A~m_ԂɂmTOR1sƁC1jULK1Li[[̂̊㏸Ê̋ߖTɈڍsĎʁC2jPI3Li[[̂ɂPI3P̎YDYꂽPI3PɁC3jPI3P^pNłWIPIp[gi[łAtg2ƂƂɃI[gt@S\[̌`̏ɏWςD4j^pNłAtg9L̓SŴ`鏬EɋǍ݂ߓIɃI[gt@S\[ɏWςD5jAtg12Ln̓rL`ľAtg12Atg5LDAtg12-Atg5̂Atg16L3ҕ̂`ĊuɋǍ݂LC3ƃzXt@`WG^m[A~Ƃ̃A~ȟ`̈ʒu߂ƂƂɁCu̐LɊ^D6jЂƂ̋LnłLC3́CproLC3ƂĐꂽɃVXeCveA[[łAtg4BɂC[GlyIon^ɕϊiLC3-IjDLC3-IAtg7ɂATPɈˑIɃAfjꃆrL`yfl^pNłAtg3ɓ]ڂD̂̂CLC3-IC[GlyƊũzXt@`WG^m[A~ƂAtg12-Atg5-Atg16L̂A~hꂽLC3-IIɂȂDLC3-II͊u̐LѕɊ^D
PEFzXt@`WG^m[A~D
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2014/06/Komatsu-3.e006-Fig.1.jpg" target="_blank">[Download]</a></div>[hs_figure id=1&amp;image=/wordpress/wp-content/uploads/2014/06/Komatsu-3.e006-Fig.1.png&amp;caption=fig1-caption-text]

@ȂCoyɂI[gt@W[̌ɂẮC<a href="http://leading.lifesciencedb.jp/1-e005/" target="_blank">rؕۍOEǓT, ̈Zr[, <strong>1</strong>, e005, 2012</a> QƂꂽD

<h2>1DI[gt@W[̊ї}̋@\</h2>
@I[gt@W[͂ɃCXVOiуA~m_VOiɉmTOR1̊ɂ}<a href="#R2"><sup>2-4)</sup></a>DCXVOi̓NXI PI3Li[[-AKToHCTSC2_邱Ƃɂ肻̊}DTSC2GTPase^pNiGTPase activating proteinFGAPjƂĒᕪqG^pNłRheb̊𕉂ɐ䂷<a href="#R5"><sup>5-8)</sup></a>DāCAKTɂTSC2̗}mTOR1̊𑣐ii<a href="#F2">}2</a>jDCA~m_VOiiƂɁCCVуO^~jɂᕪqG^pNłRagGDP^GTP^ւƕϊƁCRagmTOR1̍\^pNłRaptorƌDɁCRag̓\\[ɋǍ݂RagulatorƂ΂镡̂Ƒݍp邱ƂɂmTOR1\\[ɂȂƂ߂DŏIIɁC\\[ɑ݂RhebmTOR1Ƃ邱ƂɂmTOR1̊i<a href="#R9"><sup>9-11)</sup></a>DCVtRNAVe^[[RagGTPase^pNƂċ@\CCVɗUmTOR1̊Ɋ^DO^~̓O^~i[[ɂO^~_ɕϊCɁCO^~_fqhQi[[ɂEA~mɂ胿PgO^_ƃAjAɂȂDPgO^_RagGTP^ւ̕ϊ𑣐imTOR1<a href="#R12"><sup>12-14)</sup></a>D̂ƂCCV̓O^~_fqhQi[[AXebNɊĂDC\\[ɑ݂A~m_̓\\[ɋǍ݂V^ATPasemCV^ATPaseRagulatorƂ̉邢͉𗣂𐧌䂷邱ƂɂmTOR1̊𐧌䂷<a href="#R15"><sup>15,16)</sup></a>DmTOR1ULK1Li[[̂ƑݍpCULK1Atg13_I[gt@W[͗}<a href="#R17"><sup>17)</sup></a>i<a href="#F2">}2</a>jDȂ킿CCX邢̓A~m_RƃI[gt@W[͗eՂɎNi<a href="#F2">}2</a>jDi؂ł̓CXɂCC̑ł̓A~m_ɂI[gt@W[}ĂĈɂăI[gt@W[mTOR1ɂgDƂɈقȂq@\ɂ萧䂳Ă<a href="#R18"><sup>18)</sup></a>DOR[XRATPAMP/ATP䂪㏸ČʁCAMPKDAMPKRaptor̃_邢TSC2̃_mTOR1sI[gt@W[U<a href="#R19"><sup>19,20)</sup></a>D܂CAMPKULK1Beclin 1𒼐ڂɃ_<a href="#R21"><sup>21,22)</sup></a>DāCAMPKmTOR1ɈˑIɂˑIɃI[gt@W[i<a href="#F2">}2</a>jD

<a name="F2"></a><div id="fig2-caption-text" style="display: none;"><strong>}2@mTOR1ɂI[gt@W[̐̋@\</strong>
A~m_VOiɂmTOR1̊́CRaĝRagulatorɏW񂳂Đ䂳DO^~̓PgO^_ɕϊꂽ̂CGTP^Ragւ̕ϊ𑣐iDCVtRNAVe^[[͍זEɂăCV̔ZxmZT[Ƃċ@\CCV̔ZxԂłRagGTPase^pNƂĂ͂炭D\\[ɂA~m_̔Zx̓\\[ɋǍ݂V^ATPaseɂ芴mDA~m_̔ZxႢԂłV^ATPaseRagulatorƑݍp邱ƂɂRagmTOR1Ƃ̌}DV^ATPaseRagulatorƂ̌̓A~m_̎hɂ𗣂D炷ׂĂ̔mTOR1̊ɂ͂炫I[gt@W[}DAMPKAMP/ATP̏㏸ɂƂȂDAMPKTSC2̃_邢mTOR1̍\^pN̂ЂƂłRaptor̃_mTOR1sD
PF_D
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2014/06/Komatsu-3.e006-Fig.2.jpg" target="_blank">[Download]</a></div>[hs_figure id=2&amp;image=/wordpress/wp-content/uploads/2014/06/Komatsu-3.e006-Fig.2.png&amp;caption=fig2-caption-text]


<h2>2DI[gt@W[̐@\</h2>
@I[gt@W[̂Ƃ{IȐ@\́CQւ̓Kłi<a href="#F3">}3a</a>jDłɏqׂƂCI[gt@W[͒A~m_Ԃ邢͒CXԂɂĈߓIɗUזE̐𕪉D⎉ƈقȂA~m_v[͂킸łiqg̐l̏ꍇC^pNɕKvȃA~m_ʂ1300`400 gł̂ɑ΂CA~m_v[͖100 gȂjCQɉI[gt@W[ɂA~m_̋dvł邱Ƃ͗eՂɑzłDƂ΁C}EX̐Ve͑ٔՂ̉h{̋₽o̒ɈߓIɃI[gt@W[UA~m_v[ێDSgɂ<em>Atg5</em>`q}EX͏o̒̋Q̍ۂɑgDьɂďdĂȒA~m_ǏɂCꂪƂȂo24ԈȓɎS<a href="#R23"><sup>23)</sup></a>Dł́CI[gt@W[ɂ萶A~m_͂ǂȂ̂낤H@oỹI[gt@W[s\ψّ̂͋Q̍ۂɃ~gRhAċz^pNR_^pN̐̕sSЂNƂC1ɁCQɉ̃^pN̐̂߂ɗpƍlD܂CA~m_̓A~m]ڔA~m_ӂɂsr_CTCAHԑ́CAZ`CoAƂȂDA~m_͂̕[oHɂ蓜VCb_CGlM[YɊ^DۂɁC̑ɓٓIAtg7mbNAEg}EX̉͂CI[gt@W[ɂ萶A~m_͓Vɗp邱Ƃ炩ɂȂĂ<a href="#R24"><sup>24)</sup></a>DזEł̓I[gt@W[ɈˑA~m_TCAHԑ̂̋̐ɏdv炵<a href="#R25"><sup>25)</sup></a>D܂CAtg5mbNAEg}EXɂĂAMPKĂCVjQĂ邱Ƃ<a href="#R23"><sup>23)</sup></a>D󐸂̒ɂI[gt@W[͊CɗR^pN𕪉C̏ɕKvȃ^pN̐̂߂̃A~m_<a href="#R26"><sup>26)</sup></a>D̂悤ȃI[gt@W[́CזE̐IIʂɃI[gt@S\[Ɏ荞ŕƂĂD

<a name="F3"></a><div id="fig3-caption-text" style="display: none;"><strong>}3@I[gt@W[̐@\</strong>
iajQɉI[gt@W[ɂYꂽA~m_́CQXgXɂ萶_fɑΉXJxW[^pNQւ̓KɕK{̃^pN̐ɗpD܂Csr_ւ̕ϊVCTCAH̒ԑ̂ւ̕ϊ_I_ɂvD
ibjP퐫̈ێDȏԂɂċNĂI[gt@W[͍זEɂӉ]ɂ^pNIKl̕iǗSDPIȃI[gt@W[ُ͕̈ϐ^pN̑ЂNDזEɐN׋ۂ̓rL`ăI[gt@W[ɂIIϋɓIɔrDF̗򐫈`p[L\ǎ`qł<em>PARK2</em>`qɃR[h郆rL`K[[ParkińCF̗򐫈`p[L\a̕ʂ̌`qł<em>PARK6</em>`qɃR[hPINK1ƋCُȃ~gRhÃrL`𑣐iD̃rL`I[gt@W[ɂُȃ~gRhA̔r̃VOiɂȂƍlĂDSqstm1/p62͍זEɐN׋ۂُȃ~gRhAɃrL`ɈˑċǍ݂CrL`K[[A_v^[^pNKeap1̍\̂Ɋu邱Ƃɂ]ʈqNrf2DSqstm1/p62Keap1͍זEɐN׋ۂُȃ~gRhAƂƂɃI[gt@W[ɂ蕪DāCI[gt@W[ُ̈́Cُ^pN̒~ρCRƉȕQCُȃ~gRhA̒~ρCāCPINrf2̊ЂND͊ǁC_oϐCȂǂ̕aԂ̔ǂɖڂɊ֗^D
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2014/06/Komatsu-3.e006-Fig.3.jpg" target="_blank">[Download]</a></div>[hs_figure id=3&amp;image=/wordpress/wp-content/uploads/2014/06/Komatsu-3.e006-Fig.3.png&amp;caption=fig3-caption-text]

@h{\ɑ݂ꍇłCꃌxł̍PIȃI[gt@W[͋NĂi<a href="#F3">}3b</a>jD̍PIȃI[gt@W[̊͒Ⴂxł͂邪CזẼIKl^pN̐VӂSDCȂgDɓٓIȃI[gt@W[}EX̉͂ɂCQ~gRhA͂߂ƂُȃIKl⃆rL`ɗz̃^pNÏŴ̒~ςI[gt@W[̗}ɂ董iCldĂȎЂN邱ƂꂽDI[gt@W[͍זẼIKl^pN𖳍ׂɎ͂񂾃I[gt@S\[\\[ƗZċNIIȕnƑz肳ĂC1990N㔼2000NOCoy⃁^m[yp͂CꂼCA~myv`_[[̂yILV\[I[gt@W[̕q@\ɈˑđIIɉtEiyɂāC\\[ɑIKljɗAĂ邱Ƃ炩ɂȂ<a href="#R27"><sup>27,28)</sup></a>D2004Nɂ́CזEɐNA^AۂI[gt@S\[ɑIIɎ荞܂ꃊ\\[ɂĎEۂ邱Ƃ񍐂ꂽ<a href="#R29"><sup>29)</sup></a>D2005Nɂ́CrL`LC3^pNSQSTM1/p62I[gt@W[ɂ郆rL`^pNÏŴ̔r@\񏥂ꂽ<a href="#R30"><sup>30)</sup></a>D𓯂āCI[gt@W[}EX̑gDɂ鋤ʂ̓ƂāCSqstm1/p62邵~ςCrL`zSqstm1/p62z̃^pNÏŴ`Ă邱Ƃ<a href="#R31"><sup>31)</sup></a>D܂2009Nɂ́Coyɂă~gRhAɑ΂IIȃI[gt@W[ɕK{̃^pNƂAtg32ꂽ<a href="#R32"><sup>32)</sup></a>DɁCNp[L\ǎ`qɃR[h郆rL`K[[Parkinɂ~gRhAO^pÑrL`CI[gt@W[ɂϐ~gRhȀN邱Ƃ񍐂Ă<a href="#R33"><sup>33)</sup></a>D̑III[gt@W[͍זẼXgXɉėUIɋND̐N̂ɁCIII[gt@W[ُ̈̓p[L\aCǁC̔ǂɖڂɊ֗^邱Ƃ炩ɂȂĂi<a href="#F3">}3b</a>jD

<h2>3DI[gt@W[Ǝ</h2>
@I[gt@W[֘A`qIII[gt@W[Ɋ֗^`q̕ψقɂN`CN[aCp[L\aCSENDAaCViciǌQCāCɂďqׂi<a href="#F4">\1</a>jD

<a name="F4"></a><div id="fig4-caption-text" style="display: none;"><strong>\1@I[gt@W[Ɋ֘A`</strong>
<a href="http://leading.lifesciencedb.jp/wordpress/wp-content/uploads/2014/06/Komatsu-3.e006-Table-1.jpg" target="_blank">[Download]</a></div>[hs_figure id=4&amp;image=/wordpress/wp-content/uploads/2014/06/Komatsu-3.e006-Table-1.png&amp;caption=fig4-caption-text]

@<strong>N[a</strong>́CǂɏdĂȉǂ邢͒ᇂЂNs̉ǐłDN[a̔ǂɂ́Câ̊CRƉüُCH̐ɂ钰ǔSُ̈ȂǁCGȊvłƑz肳ĂD2007NCRAAtg^pNR[h`q̂ЂƂ<em>ATG16L1</em>`q̔񓯋`uɃN[aƂ̋ւ̂邱Ƃ񍐂ꂽ<a href="#R34"><sup>34,35)</sup></a>DATG16L1N[ɃRChRC̈CC[WDs[gDATG12-ATG5̂Ƒݍp3ҕ̂`CLC3LnɂărL`K[[l^pNƂċ@\<a href="#R36"><sup>36)</sup></a>Doꂽ񓯋`uWDs[gN[ɈʒuĂDWDs[g͏oyATG16ɂ݂͑CȂƂC}EX̐ۉזEł̓I[gt@W[̊ɉeȂƂ񍐂Ă<a href="#R37"><sup>37,38)</sup></a>Dŋ߁CQȂǂ̑ӃXgX̂Ƃł͂̕ψٌ^Atg16L1̓JXp[[3ɂؒfeՂɂCI[gt@W[̊シ邱Ƃ񍐂ꂽDψٌ^Atg16mbNC}EXɒ׋ۂ̂ЂƂł<em>Yersinia</em>׋ۂƁCI[gt@W[ɂ׋ۂ̔rsꂸCǐTCgJC̕o<a href="#R39"><sup>39)</sup></a>D̂قɂCAtg16L1}Nt@[W̓OA׋ۂɉĉߏȃC^[CL1уC^[CL18YǔЂNƁCAtg16L1ᔭ}EXł͍Rۃyv`hȂǂ𕪔傷鏬PanethזEɂĕ̌`sSѕُ킪F߂邱ƁCI[gt@W[ƏẼXgX̗jQ邱Ƃɂ͂߂ĒЂN邱ƂȂǁCN[a̔ǂɃI[gt@W[ُ̈킪֗^Ƃ񍐂~ς<a href="#R40"><sup>40-42)</sup></a>D
@<strong>p[L\a</strong>́C_o`Błh[p~Y钆]̃h[p~j[̕ϐђEɂƂȂĈɂh[p~̊ܗLʂ̌ɋND̂ɂh[p~̌͑]玿Ot̉^Ƒ]j߂郋[vH̋@\ЂNCCŏkCUȂǂ̏dĂȉ^Q𔭏ǂDp[L\ȃ啔͌ʔł邪C̈`qψقɋNƑp[L\aDF̗򐫈`p[L\ǎ`qł<em>PARK2</em>`qɃR[h郆rL`K[[ParkinCϐ~gRhAɓ]ڂ~gRhAO^pNrL`ƁCꂪƂȂI[gt@W[ɂُȃ~gRhȂIIȔri}Cgt@W[j̎N邱Ƃ񍐂ꂽ<a href="#R33"><sup>33)</sup></a>i<a href="#F3">}3b</a>jDParkiñ~gRhAւ̋Ǎ݂́CF̗򐫈`p[L\a̕ʂ̌`qł<em>PARK6</em>`qɃR[hPINK1Ɉˑ<a href="#R43"><sup>43-47)</sup></a>D~gRhAǍ݃VOiіђʗ̈Z-XIjLi[[łPINK1́Cʏ̓~gRhAɑ݂veA[[PARLɂؒfveA\[ɂ蕪<a href="#R48"><sup>48,49)</sup></a>DCdʂ~gRhAłPINK1̓~gRhAOɂƂǂ܂ĎʁCPINK1͎ȃ_ɈˑParkin~gRhAւƃN[g<a href="#R50"><sup>50)</sup></a>Dɂŋ߁CPINK1rL`_C̃rL`̃_Parkin̊ɕsł邱Ƃ<a href="#R51"><sup>51)</sup></a>i<a href="http://first.lifesciencedb.jp/archives/8735" target="_blank">V_r[</a> łfځjDp[L\å҂ɗRψقParkinPINK1͂̉ߒɈُ<a href="#R45"><sup>45)</sup></a>DāCPINK-ParkinoH}Cgt@W[ُ̈킪_f̒~ςЂNCh[p~j[ăp[L\a̔ǂɂƑz肳D̉x悤ɁC~gRhÄُƃp[L\aƂ̊֘A͌Â񍐂ĂDƂ΁Cp[L\å҂ɂāC~gRhADNǍCċz̒ቺ~gRhA̒~ρCɂƂȂ_f̑mFĂDCPINK-ParkinoH̓}Cgt@W[̗Uł͂ȂCɃveA\[ɂ~gRhAO^pN̕i~gRhAO^pN̕iǗjɋ@\ƂlĂ<a href="#R52"><sup>52)</sup></a>DPINK-ParkinoH͓IɌC~gRhA̕܂ŃtH[͏ȂC̏ڍׂȌKvƎvD
@<strong>SENDAa</strong>́C]̍ђWɂS̒Ƒ]̈ޏkƂȂ_oϐłiSENDAFstatic encephalopathy of childhood with neurodegeneration in adulthoodjDŋ߁CSENDAå҂̃GN\[͂CoỹI[gt@W[֘A`qł<em>ATG18</em>`q̃qgɂ4̃zOi<em>WIPI1</em>`q`<em>WIPI4</em>`qĵЂƂł<em>WDR45</em>/<em>WIPI4</em>`qɐVK̕ψق肳ꂽ<a href="#R53"><sup>53,54)</sup></a>i<sup>54)</sup> ́C<a href="http://first.lifesciencedb.jp/archives/6706" target="_blank">V_r[</a> łfځjDoyATG18PROPPINt@~[̂ЂƂŃvy\WD40hC܂݁CzXt@`WCmVg[-1,4,5-gX_iPI3Pjу\\[ɋǍ݂zXt@`WCmVg[-3,5-rX_ƌ<a href="#R55"><sup>55-57)</sup></a>DATG18ɂ2̃zXt@`WCmVg[ʂ݂CPI3Li[[ɂYꂽPI3PɈˑăI[gt@S\[̌`ʒuɃN[g<a href="#R58"><sup>58-61)</sup></a>DSENDAå҂Pꂽp苅lזEɂWDR45/WIPI4ɌĂCI[gt@S\[̌`Ɋ֗^Atg9L1LC3ُ̈Ȓ~ρiI[gt@S\[ԑ̂̒~ρjCсCI[gt@W[̊̒ቺmFꂽ<a href="#R54"><sup>54)</sup></a>D̂Ƃ́CRAAtg^pNR[h<em>WDR45</em>/<em>WIPI4</em>`qɂψق_oϐ̔ǈqƂȂĂ邱ƂӖ邪CI[gt@W[̏Qǂ̂悤ɂēS̒ЂN̂CȂj[݂̂ŉeF߂邩͕słCȂ͂KvłD<em>WDR45</em>/<em>WIPI4</em>`qXF̂ɈʒuĂCXF̂̕sɂ菗SENDAå҂WDR45/WIPI4̋@\UCNɎĂDjłWDR45/WIPI4͊SɌĂ邪C̒jႪ񍐂Ă<a href="#R53"><sup>53,62)</sup></a>DWDR45/WIPI4̋@\̌WIPI1`WIPI3ɂ肠x͕⊮ƍlC킸ȃI[gt@W[̊̌オaԂ̔ǂɏ\ł邱ƂD
@<strong>ViciǌQ</strong>́C򐫈`̑nłC]̌`sSCCS؏ǁCƉusSCFf̌ƂDViciǌQ̊҂̃GN\[͂ɂC<em>EPG5</em>`qɕ̕ψق𓯒肳ꂽ<a href="#R63"><sup>63)</sup></a>D<em>EPG5</em>`q͐ɂăI[gt@W[̊̕jQwWƂXN[jOɂ㐶ɓٓIȃI[gt@W[֘A`qƂē肳ꂽ<a href="#R64"><sup>64)</sup></a>DMލזEɂ<em>EPG5</em>`qmbN_EƓdqx̍I[g\\[Ԃɂ킽~ς邱ƂCEPG5̓I[g\\[̐nɊ֗^ƍl<a href="#R65"><sup>65)</sup></a>DۂɁCViciǌQ̊҂ɗRۉזEыؓł̓I[gt@W[̊̒ቺƂƂɁCI[gt@W[̑IIȊłSQSTM1/p62NBR1̒~ςmFD[ƂɁCViciǌQ̊҂ɗRۉזEł̓I[gt@S\[̌`𐧌䂷AKTFOXO3Ȃǂ̏㗬^pNeĂ<a href="#R63"><sup>63)</sup></a>DāCViciǌQł̓I[gt@W[̂܂܂ȃXebveĂ\DɁCEPG5mbNAEg}EXɂ͑]玿̓̃j[wѐҐ̉^j[ɓٓIȏQmFCؓ̏_oCؑ@ۂ̈ޏkC̒ቺC؈ޏkdǗl̏ǏD<em>EPG5</em>`q}EX̃j[уOAזEłSqstm1/p62z^pNуrL`^pN~ςĂCI[gt@W[̊̒ቺF߂ꂽ<a href="#R65"><sup>65)</sup></a>D̎́C<em>EPG5</em>`q̕ψقɂViciǌQ̔ǂɃI[gt@W[̕sS֗^邱ƂD

<h2>4DI[gt@W[Ƃ</h2>
@I[gt@W[̓CXVOi`BoHуA~m_VOi`BoH̉ɈʒumTOR1ɂ蕉ɐ䂳Ăi<a href="#F2">}2</a>jDCXVOi`BnɊ֗^邪`q邢͂}`q̕ψق̓CXVOi̍PIȊЂNƂCזEɂI[gt@W[̗}ĂDCmTOR1͑lȍזE@\𐧌䂵Ă邽߁CmTOR1̊ɂI[gt@W[̗}ǂ܂Ŏᇂ̌`ɂĂ邩͕słD1999NɁCoy<em>ATG6</em>/<em>VPS30</em>`q̍ɂzOł<em>BECN1</em>`q}`qł邱Ƃ񍐂ꂽ<a href="#R66"><sup>66)</sup></a>DBECN1̓qg̓ȂǂɂĔቺĂCɁCBecn1wembNAEg}EXł͂܂܂ȎᇂR邱ƂCI[gt@W[͎ᇂ̌`}ĂƍlĂ<a href="#R66"><sup>66)</sup></a>DC<em>BECN1</em>`q̃R[hBeclin 1̓I[gt@W[ł͂ȂGhTCg[VXɂ֗^鑽@\^pNł邽߁CBecn1wembNAEg}EXp̌ʂ^ɃI[gt@W[sS̕\^Ă̂^₪cĂD
@2011NɁCI[gt@W[ɓ`qσ}EXᇂ`邱ƂCᇂ̗}I[gt@W[̐IȈӋ`̂ЂƂƂĊmł̂ɂȂD<em>Atg5</em>`qSgɂăUCNɌ}EX́C7JŊ̑ɏȎᇂώ@CƂƂɎᇂ̑傫ѐ͑C16JɂĊ͎̑ᇂɂ肵߂ꂽ<a href="#R67"><sup>67,68)</sup></a>D[ƂɁC̃UCN}EX͑Sgɂ<em>Atg5</em>`qĂɂ炸C̑ɂ̂ݎᇂ`ꂽ<a href="#R68"><sup>68)</sup></a>DقړľʂC̑ɓٓIAtg7mbNAEg}EXɂĂώ@Ă<a href="#R67"><sup>67)</sup></a>Dڂׂ_ƂāCBecn1wembNAEg}EXƂ͈قȂC<em>Atg5</em>`q邢<em>Atg7</em>`q̌ɂ`ꂽ̑̎ᇍזEɂ͊jِ̈ȂCʂɌǂămN[iɑBKIȔz⑝Bp^[`ǐ̎ᇂłCق̑ւ̓]ڂmFȂ<a href="#R67"><sup>67,68)</sup></a>D<em>Atg5</em>`q邢<em>Atg7</em>`q̎זEɂāCc~gRhAyILV\[̒~ρCDNA̎_Qm̕s萫F߂<a href="#R67"><sup>67,68)</sup></a>DɕۂׂyILV\[@\sSɂ~gRhAI[gt@W[ɂ蕪Ȃ߂ɍזEɒ~ςČʂƂĊ_f킪ߏɐCDNAUᇂ̌`𑣐iĂ\D
@Sqstm1/p62ᇉюᇂ̐isɊ֗^DSqstm1/p62̓I[gt@S\[ɋǍ݂^pNłLC3Ɍ^pNłCI[gt@W[ɂPIɕĂ<a href="#R30"><sup>30)</sup></a>DāCI[gt@W[gDɂČɒ~ςDŋ߁CtזE̊҂5ɂ<em>SQSTM1</em>/<em>p62</em>`q܂ޗ̈悪`qdĂ邱ƁCSQSTM1/p62̔㏸ᇂ̌`Ƒւ邱Ƃ񍐂ꂽ<a href="#R69"><sup>69)</sup></a>D܂C<em>SQSTM1</em>/<em>p62</em>͂`qłDSQSTM1/p62͎ᇉ邢͎ᇂ̐isɂǂ̂悤Ɋ֗^̂낤H@Sqstm1/p62͕̃VOi`B^pNƑݍpXJtH[h^pNłCTRAF6Ƃ̌NF-BVOi̊⃆rL`JXp[[-8Ƃ̑ݍpA|g[VX̑iȂǍזE̐𐧌䂵Ă<a href="#R70"><sup>70)</sup></a>DNF-BVOi͎̊ᇂ̌`Ɋ֗^邱ƂCSqstm1/p62̒~ςɂNF-BVOi̍PIȊᇂ̌`̗vƂĂDC<em>SQSTM1</em>/<em>p62</em>̌ɂNF-BVOi̗}RasU̔xB̌`}邱ƂCPIKras̊ɂSQSTM1/p62̘̔iXǑB̔BɊ֗^邱Ƃ񍐂Ă<a href="#R71"><sup>71,72)</sup></a>D
@Sqstm1/p62Cullin3^rL`K[[̃A_v^[^pNKeap1Ƃ̑ݍpē]ʈqNrf2CXgẌ`qU<a href="#R31"><sup>31)</sup></a>i<a href="#F3">}3b</a>jDKeap1Ƃ̌mTOR1ɂSqstm1/p62̃_ɂ葝<a href="#R73"><sup>73)</sup></a>i<a href="http://first.lifesciencedb.jp/archives/7692" target="_blank">V_r[</a> łfځjDdvȂƂɁCxȂǂɂčPINrf2Ă邪זÉCXgX`q݂̂Ȃ炸Cyg[X_oH-vkNI`hoHO^~ӂ𐧌䂷yf̈`qUC炪ᇂ̑BĂ<a href="#R74"><sup>74)</sup></a>i<a href="http://first.lifesciencedb.jp/archives/5262" target="_blank">V_r[</a> łfځjDSqstm1/p62~ςNrf2͍PIɊČʁCᇍזȆB𑣐iƍlD̂Ƃ́C̑ɓٓIAtg7 Sqstm1/p62_umbNAEg}EXɂāCᇂ̌`啝ɗ}邱ƂƈvD̎́CI[gt@W[̌ɂƂȂyILV\[@\sSɂ~gRhA̒~ςɂ銈_f̑CсCSqstm1/p62̒~ςɂVOi`Bُ̈킪Cᇂ̌`ѐišł邱ƂD
@邵BԂזE͏\ȌǐVƂȂ킸C_f邢͒OR[XƂӃXgX̂Ƃł̐]VȂĂD܂CזE͂̑Bێ邽߁CA~m_CCb_Ȃǂ葽KvƂCȂ킿CזE͑ӂ̗v߂čԂɂ<a href="#R75"><sup>75)</sup></a>DI[gt@W[͎ᇂ̌`}CᇉĂ܂זEɂĂ͉h{邱Ƃɂӂ̗v݂̑BɍvĂDƂɁC90<em>Ras</em>`q̕ψق̔F߂X⊈^Rasɂ`]זEȂǂł́CI[gt@W[PIɘigI[gt@W[ˑh̏ԂɂȂĂ<a href="#R25"><sup>25,76)</sup></a>D̃I[gt@W[̊̕q@\͂قƂǂ킩ĂȂCI[gt@W[jQƁCX̑B}CَڐAɂᇌ`̗}CX}EXf̎ᇂ̑ޏk݂<a href="#R25"><sup>25,76)</sup></a>D̂悤ȃI[gt@W[̑jQɂᇂ̗}ʂ́CMycŨp|I[}ECX^TRɗU̓BᇂɂĂF߂<a href="#R77"><sup>77,78)</sup></a>D
@I[gt@W[jQXזEł́C_f̑CDNA̒~ρC킦āC炭TCAHԑ̂̋̌ɂ_I_̒ቺώ@<a href="#R25"><sup>25)</sup></a>DāĈזEɂčPIɘiĂI[gt@W[́CA~m_邱ƂɂTCAHԑ̂̎Y𑣐iƂƂɁC~gRhA̕iǗɂ肪זE̐ёBɊ^ĂƑz肳DC<em>Ras</em>`q̃I[gt@W[ւ̊֗^͕GłDƂ΁CRas̉ߏ蔭ɂUI[gt@W[́Cqg̗\wזEɂĂ͍זECۉזEɂĂ͍זEV𑣐i<a href="#R76"><sup>76,79,80)</sup></a>D܂CʓIRAS̊mF鍕FɂẮCmTOR1̍PIȊɂI[gt@W[}Ă炵DāCF̓A~m_v[̌ɉI[gt@W[UłזEЂN<a href="#R81"><sup>81)</sup></a>DX̂ɂI[gt@W[̐IȖ́CXe[WCāC`wIȔwiɂقȂ̂낤DCŋ߁Cp53̗̌LɂXɂI[gt@W[̖قȂ邱Ƃ炩ɂȂ<a href="#R82"><sup>82)</sup></a>D

<h2></h2>
@I[gt@W[֘A`q̓͂߁CI[gt@W[ɂ{l̍v͑傫D݁CĂуAWÅeł̓I[gt@W[̌ɂĊbx݂̂Ȃ炸gX[ViT[`ɍsĂCՏւ̉pɊւĂ킪͌oqĂ銴DƂɁCזEɂĂ̓I[gt@W[ɂA~m_̋~gRhAȂǂ̃IKl̕iǗ̑BɌIłC̍R܂ƃI[gt@W[jQ܁imɂ́C\\[_jQ܁j킹񎡗Â̗ՏłɉĂɂĊJnĂD܂CEŃI[gt@W[ɓٓIȊ܂ёjQ܂̃XN[jOsC͓xł̌ʂmFĂDCI[gt@W[̗Տւ̉pɂ͂̖_cĂDI[gt@W[̕q@\ɂ͖𖾂̓䂪܂RςĂC̑jQ邢͘iɂǂ̂悤ȕp̂słD݂܂ŁCI[gt@W[̊j^[ł}[J[v[u݂C̔肪łȂD`qϓ̉͂ɂ肨̂̂̑gDɂI[gt@W[̐@\̑؂͔邪Cqg̕aԂɂ邻̈Ӌ`͂قƂǎ̏ԂłCȂ͂Kvł낤D

<h2> </h2>
<ol>
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<li id="R8"><span class='au'>Zhang, Y., Gao, X., Saucedo, L. J. et al.</span>: <span class="ti">Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins.</span> <span class='so'>Nat. Cell Biol., 5, 578-581 (2003)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/12771962" target="_blank">PubMed</a>]</span></li>
<li id="R9"><span class='au'>Kim, E., Goraksha-Hicks, P., Li, L. et al.</span>: <span class="ti">Regulation of TORC1 by Rag GTPases in nutrient response.</span> <span class='so'>Nat. Cell Biol., 10, 935-945 (2008)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/18604198" target="_blank">PubMed</a>]</span></li>
<li id="R10"><span class='au'>Sancak, Y., Bar-Peled, L., Zoncu, R. et al.</span>: <span class="ti">Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids.</span> <span class='so'>Cell, 141, 290-303 (2010)[<a href="http://www.ncbi.nlm.nih.gov/pubmed/20381137" target="_blank">PubMed</a>]</span></li>
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</ol>
<div class="au-profile">
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<span class="author">R  riShun Kageyamaj</span>
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