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ޣᐔᚑ㧞㧜ᐕ㧤ᧃ߹ߢߩ⎇ⓥᚑᨐޤ ࡚࡚ࠪ࠙ࠫ࠙ࡃࠛ5⚦⢩ࠍࡕ࠺࡞♽ߣߒߡࠛࡂޔ⣀ᒙ:ㆮવሶ↥‛(/4㧔F(/4㧕߇ᒻ ᚑߔࠆⶄวߦ․⇣⊛ߥዊಽሶ40#ߩหቯࠍ⹜ߺߚޕF(/4ߪ4+5%ਛᩭ࿃ሶ#TIQPCWVGⰮ⊕ ⾰ߩ৻ߟߢࠆ#)1ߣ⋧↪ߔࠆߎߣ߆ࠄޔߕ߹ޔ#)1ⶄวߦ߹ࠇࠆዊಽሶ40#ߩ หቯࠍⴕߞߚ⚿ߩߘޕᨐⶄߩߎޔวߦߪౝᕈUK40#߇߹ࠇߡ߅ࠅߩߘޔᄙߊ߇࠻ ࡦࠬࡐ࠱ࡦ㧔ォ⒖࿃ሶ㧕ߦ↱᧪ߒߡߚ⯻✢ޕએᄖߢౝᕈUK40#߇หቯߐࠇߡߚ߇ޔ 㜞╬⌀ᩭ↢‛ߦ߅ߌࠆᦨೋߩౝᕈUK40#ߩหቯߢࠆߩߎޔߚ߹ޕᚑᨐߪ#)1߇࠻ࡦ ࠬࡐ࠱ࡦߩᛥߦ㑐ਈߒߡࠆߣߎߣࠍ␜ໂߒޔߡߞ߇ߚߒޔF(/4߽ߘߩ⚻〝ߢᯏ⢻ߔ ࠆน⢻ᕈ߇ߢߡ߈ߚ৻ޕᣇޔห᭽ߩ⸃ᨆࠍࡅ࠻⚦⢩ߢ߽ⴕ߁ὑߦ(࠻ࡅޔ/4߿ࡅ࠻#)1 #)1ߦኻߔࠆ∉ᴉ㒠ᴺߦ↪น⢻ߥࡕࡁࠢࡠ࠽࡞᛫ߩࠬࠢ࠾ࡦࠣࠍㅴࡅޔ ࠻#)1#)1ߦኻߔࠆࡕࡁࠢࡠ࠽࡞᛫ࠍᚑߔࠆߎߣ߇ߢ߈ߚޕ ޣ㧳㧺㧼ߣߩ㑐ㅪ㧳㧺㧼߳ߩ⽸₂ޤ 㨍㧕ォ౮ᓮߩ⸃ߦ㑐ㅪߔࠆ⎇ⓥᚑᨐ ࠻ࡦࠬࡐ࠱ࡦߩ⊒ߪᨴ⦡ߩୃ㘼㧔ࡋ࠹ࡠࠢࡠࡑ࠴ࡦൻ߿&0#ߩࡔ࠴࡞ൻ㧕ࠍㅢߒ ߡォ౮ࡌ࡞ߢᛥߐࠇߡࠆߎߣ߇⍮ࠄࠇߡࠆߩ᧪↱ࡦ࠱ࡐࠬࡦ࠻ޕౝᕈUK40# ߩ⊒ߪࠄࠇߎޔዊಽሶPQPEQFKPI40#߇․ቯᨴ⦡㗔ၞࠍୃ㘼ߔࠆߚߩࠟࠗ࠼ಽሶ ߣߒߡᯏ⢻ߔࠆน⢻ᕈࠍ␜ໂߔࠆޕ 㨎㧕❑ゲ⎇ⓥ㧔ߪᮮゲ⎇ⓥ㧕߳ߩ⽸₂ߦ❬߇ࠆ⎇ⓥᚑᨐ ᛫ࠍ↪ߚ࠲ࡦࡄࠢ⾰ዊಽሶPQPEQFKPI40#ⶄวߩ♖ᴺ߅ࠃ߮ߘߩⶄว߆ ࠄߩዊಽሶPQPEQFKPI40#ߩන㔌หቯᴺࠍ⏕┙ߒߚߩࠄࠇߎޕᛛⴚߪᓟ߹ߔ߹ߔ㊀ⷐ ߣߥࠆOK40#ߦઍߐࠇࠆዊಽሶPQPEQFKPI40#ߩ⎇ⓥߦᭂߡ↪ߢࠆޕ ޣᒰ⎇ⓥߦ㑐ߒߡᵴ↪ߒߚ⎇ⓥ࠺࠲࠰ࠬޤ ․ߦߥߒޕ ޣਥߥ⎇ⓥ⺰ᢥߣߘߩⷐޤ 1. Gunawardane, LS., Saito, K., Nishida, KM., Miyoshi, K., Kawamura, Y., Nagami, T., Siomi, H., and Siomi, MC. 2007. A Slicer-mediated mechanism for rasiRNA 5Άend formation in Drosophila. Science 315: 1587-1590. ᦨㄭߩRNAi㑐ㅪಽሶ⚻〝ߩ⸃ᨆ߆ࠄࠆߌ߅ߦࡓ࠭࠾ࠞࡔߩߎޔ㎛ߣߥࠆಽሶߪ 20ޯ 30 Ⴎၮ㐳ߩዊಽሶRNAߢࠆߎߣ߇ࠄ߆ߣߥߞߚࠄࠇߎޕዊಽሶRNAߪޔᄙߊߩ႐วޔ ࠲ࡦࡄࠢ⾰ⶄว߇․ቯߩᩭ㉄㈩ࠍ⼂ߔࠆὑߩࠟࠗ࠼ಽሶߣߒߡᯏ⢻ߒ․ޔቯRNA ߩಽ⸃߿⠡⸶ᛥߪߦࠄߐޔDNAߩࡔ࠴࡞ൻ߿ᨴ⦡ߩࡋ࠹ࡠࠢࡠࡑ࠴ࡦൻߦ㑐ਈߔ ࠆߥ߁ࠃߩߎޕዊಽሶRNA߇㑐ਈߔࠆㆮવሶᛥ⽎ߪޔޔ൮⊛ߦRNAࠨࠗࡦ ࠪࡦࠣߣ߫ࠇߡࠆޕRNAࠨࠗࡦࠪࡦࠣߪ․ቯㆮવሶ߹ߚߪ․ቯᨴ⦡㗔ၞߩoff ࠬࠗ࠶࠴ߣߒߡߩᯏ⢻߫߆ࠅߢߥߊࠍࡓࠝ࠹ࡠࡊޔᓸ⺞ᢛ㧔fine-tuning㧕ߔࠆߎߣߢ⚦ ⢩࠲ࠗࡊ߿⚵❱࠲ࠗࡊߩᄙ᭽ൻࠍ↢ߺߒࠎߚߞ߽߆ߒޔಽൻߒߚ⚦⢩߿⚵❱ࠍߘߩ ⁁ᘒߦ⇐߅ߊᯏ⢻߽ࠆߎߣ߇ߒߛߦࠄ߆ߣߥߞߡ᧪ߚᦨޔߚ߹ޕㄭޔฦ⒳⣲≌ ࠍᆎߣߒߡ᭽∔ߥޘᖚ⊒∝ߦRNAࠨࠗࡦࠪࡦࠣᯏ᭴ߩ⇣Ᏹ߹ߚߪ⎕✋߇㑐ਈߒߡ ࠆߎߣ߇ࠄ߆ߦߥࠅߟߟࠆޔߦࠄߐޕES⚦⢩ߦ߅ߌࠆmiRNAᓮߩ㊀ⷐᕈ߇ࠄ ߆ߦߐࠇߟߟࠅޔᓟޔRNAࠨࠗࡦࠪࡦࠣ⎇ⓥߪiPSࠍᐙ⚦⢩⎇ⓥߩ㊀ⷐߥಽ㊁ ߦߥߞߡߊߣ੍ᗐߐࠇࠆޕRNAࠨࠗࡦࠪࡦࠣߩਛᩭߣߥࠆ࠲ࡦࡄࠢ⾰࿃ሶߪ Argonauteߢࠆޔߪ⾰ࠢࡄࡦ࠲ߩߎޕㆮવሶࡈࠔࡒࠍᒻᚑߒ⚦ߩߡో߷߶ޔ⢩߿⚵ ❱ߢ⊒ߔࠆࠣ࡞ࡊߣ↢ᱺ⚦⢩♽ߦ․⇣⊛ߦ⊒ߔࠆࠣ࡞ࡊߩ㧞ߟߦಽ㘃ߐࠇࠆޕ ೨⠪ߪAGO ࠨࡉࡈࠔࡒޔᓟ⠪ߪPIWIࠨࡉࡈࠔࡒߣ߫ࠇߡࠆ࡚࡚ࠫ࠙ࠪޕ ࠙ࡃࠛߦߪAGOࠨࡉࡈࠔࡒ߇㧞⒳㘃㧔AGO1, AGO2㧕ߚ߹ޔPIWIࠨࡉࡈࠔࡒ߇ 㧟⒳㘃㧔Ago3, Aub, Piwi㧕ሽߔࠆߩߎޕౝޔPIWIࠨࡉࡈࠔࡒ࠲ࡦࡄࠢ⾰ߪpiRNA 㧔rasiRNAߣ߽߫ࠇࠆ㧕ߣ߫ࠇࠆዊಽሶRNAߣ⚿วߒ↢ޔᱺᐙ⚦⢩ߩᒻᚑߣ⛽ᜬߦ ᔅ㗇ߢࠆߎߣ߇ࠊ߆ߞߡߚ߇ޔpiRNAߩ↢วᚑ⚻〝ߪਇߢߞߚ⎇ᧄޕⓥߢߪޔ Ago3, Aub, Piwiߦߘࠇߙࠇ⚿วߔࠆpiRNAࠍන㔌ߒߩߘޔ㈩ࠍߚ⚿ᨐޔAgo3 ߦߪ ォ⒖࿃ሶߩォ౮↥‛ߦ↱᧪ߔࠆࠬࡦࠅ߹ߟޔ㎮ߦ↱᧪ߔࠆpiRNA߇, ৻ᣇޔAubߣPiwi ߦߪォ⒖࿃ሶߩኻ㎮ߦ↱᧪ߔࠆࠬࡦ࠴ࡦࠕࠅ߹ߟޔ㎮ߦ↱᧪ߔࠆpiRNA߇⚿วߒߡ ࠆߎߣ ߽߆ߒޔAgo3 ߦ⚿วߔࠆpiRNAߣAubߦ⚿วߔࠆpiRNAࠍᲧセߒߚ㓙ޔ5’ᧃ┵ ߩ 10 Ⴎၮ߇ቢోߥ⋧ᕈࠍ␜ ␜ ߔ߽ߩࡍࠕ߇ᢙᄙߊߟ߆ߞߚ⚿ߩࠄࠇߎޕᨐ߆ࠄޔ piRNAߩ 5’┵ߩᒻᚑߪpiRNAߣ⋧↪ߒߡࠆAgo3 ߣAub߇ߘߩᮡ⊛RNAಾᢿᵴᕈ 㧔Slicer㧕ࠍ↪ߡߦኻ㎮ࠍಾᢿߒว߁ࠨࠗࠢ࡞ࠍᒻᚑߒߡࠆߎߣࠍ␜ໂߔࠆޕ 2. Azuma-Mukai, A., Oguri, H., Kin, T., Qian, ZR., Asai, K., Siomi, H., and Siomi, MC. 2008. Characterization of endogenous human Argonautes and their miRNA partners in RNA silencing. Proc. Natl. Acad. Sci. USA. 105:7964-7969. ࡅ࠻ AGO ࠨࡉࡈࠔࡒ࠲ࡦࡄࠢ⾰ߦኻߔࠆ․⇣⊛ߥࡕࡁࠢࡠ࠽࡞᛫ߩᚑߔ ࠆߚߦ ࠄࠇߎޔ4 ⒳ߩ AGO ࠨࡉࡈࠔࡒ࠲ࡦࡄࠢ⾰ߦ߅ߡᲧセ⊛⋧หᕈߩૐ ࠕࡒࡁᧃ┵ 150 ࠕࡒࡁ㉄ࠍ GST Ⲣว࠲ࡦࡄࠢ⾰ߣߒߡᄢ⣺⩶ߢ⊒♖ߒࠍࠄࠇߘޔ᛫ ේߣߒߡ↪ߩߘޕߚߒ∉ࠍࠬ࠙ࡑޔᓟޔᔕࡑ࠙ࠬߩࡦࡄ▵⚦⢩ࠍ↪ߡࡂࠗࡉ ࠼ࡑࠍߒ∉ࠄ߆ߎߘޔᴉ㒠ᴺߦ↪ߢ߈ࠆ᛫ࠍࠬࠢ࠾ࡦࠣߒߚߩߘޕ ⚿ᨐޔhAGO2 ߣ hAGO3 ߦ㑐ߒߡ∉ޔᴉ㒠ᴺߦ↪ߢ߈ࠆࡕࡁࠢࡠ࠽࡞᛫ࠍขᓧ ߔࠆߎߣ߇ߢ߈ߚ㧔࿑ 4㧕 ࠄࠇߎޕ᛫ࠍ↪ߡޔ࿑ 1 ߢ␜ߒߚหߓᚻᴺࠍ↪ޔዊಽሶ RNA ࠍ♖ߒߚ㧔࿑ 5㧕 ࠄࠇߎޕዊಽሶ RNA ࠍߘࠇߙࠇࠥ࡞߆ࠄන㔌ߒࠣࡦ࠾ࡠࠢޔ ࠍⴕߩߘޔ㈩ࠍ 454 ࠪࠤࡦࠬᴺߢߘࠇߙࠇ 6 ਁ߆ࠄ 8 ਁ࠼ࠍቯߒߚޕ ߘߩ⚿ᨐ ࠻ࡅޔAGO2 ߣ AGO3 ߕࠇߦ߅ߡ߽⚿ޔวߒߡࠆዊಽሶ RNA ߩᄢㇱ ಽ߇ miRNA ߢߞߚ㧔࿑ 6㧕ޕmiRNA ߪ߶߷ోߡߩ⚦⢩ߦ⊒ߒ⚦ޔ⢩ߩಽൻ⊒↢ޔ ߐࠄߦߪᦨㄭߢߪ∔ޔᖚ߿ᐙ⚦⢩ߩᒻᚑߣߘߩ⛽ᜬߦᭂߡ㊀ⷐߥᓎഀࠍᜂߞߡࠆߎ ߣ߇ࠄ߆ߦߥࠅߟߟࠆ ࠻ࡅޕAGO2 ߣ AGO3 ߦ⚿วߒߡࠆ miRNA ࠍ⚦ߦ⺞ߴ ࠆߣޔᐞߟ߆ߩ miRNA ⒳ߦ㑐ߒߡ⚿วߦࠅ߇ࠄࠇߚޔ߫߃ߣߚޕmiR-99b ߿ miR-432-3p ߪ AGO3 ߦ৻ޔᣇޔmiR-92b ߿ miR-93 ߪ AGO2 ߦఝవ⊛ߦ⚿วߒߡࠆߎ ߣ߇ࠄ߆ߦߥߞߚ⚿ߩࠄࠇߎޕᨐ߆ࠄ ࠻ࡅޔAGO2 ߣ AGO3 ߦᯏ⢻ಽᜂ߇ࠆߎߣޔ ߹ߚޔDicer ߦࠃࠆࡊࡠ࠶ࠪࡦࠣᓟޔmiRNA ⒳ߩ㆑ߦࠃࠅޔఝవ⊛ߦࠆ⒳ߩ AGO ߦ⚿วߔࠆ⚻〝߇ሽߔࠆߎߣ߇␜ໂߐࠇߚޕ 3. Kawamura, Y., Saito, K., Kin, T., Ono, Y., Asai, K., Sunohara, T., Okada, NT., Siomi MC. & Siomi, H. 2008. Drosophila endogenous small RNAs bind to Argonaute2 in somatic cells. Nature 453: 793-797. FMR1 ߩ siRNA ಽሶ⚻〝߳ߩ㑐ਈࠍߐࠄߦᬌ⸛ߔࠆߚޔdFMR1-AGO2 ⶄวߦ⋧ ↪ߒߡࠆౝᕈߩ siRNA ߩන㔌ߣࠢࡠ࠾ࡦࠣࠍ⹜ߺߚⶄߩߎޕวౝߢޔdFMR1 ߘࠇ⥄りߦߪዊಽሶ RNA ߪ⚿วߒߡߥ߇ޔAGO2 ߦߪዊಽሶ RNA ߇ᭂߡᒝߊ⚿ วߒߡࠆߎߣ߇್ߒߚ∉ޕᴉ㒠ߩ᧦ઙࠍ᭽ߦޘᬌ⸛ߒޔEmpigen ࠍࡃ࠶ࡈࠔ ࠍ↪ߚ㓙ߦޔᄳ㔀‛ࠍᭂߡૐߊᛥ߃ࠆߎߣ߇ߢ߈ࠆߎߣ߇ࠊ߆ߞߚ᧦ߩߎޕઙߢ ࡚࡚ࠪ࠙ࠫ࠙ࡃࠛ⚦⢩↱᧪ߩၭ㙃⚦⢩ S2 ߆ࠄ∉ᴉ㒠ᴺߦߡ⋧↪ߔࠆዊಽሶ RNA ࠍหቯߒߚ ࠄࠇߎޕAGO2 ߦ⚿วߒߡࠆዊಽሶ RNA ࠍࠥ࡞߆ࠄ♖ߒޔዊಽሶ RNA ࠢࡠ࠾ࡦࠣᴺࠍ↪ߡߩߘޔߒࠣࡦ࠾ࡠࠢޔ㈩ࠍ 454 ࠪࠤࡦࠬᴺߦߡ ߚ ⚂ޕ7 ਁߩࠢࡠ࠾ࡦࠣᢿ ࠍ⺒ࠎߛ⚿ᨐࠄࠇߎޔዊಽሶ RNA㧔19ޯ22 Ⴎၮ㐳㧕ߩᄢ ㇱಽ߇ࠥࡁࡓߩ࠻ࡦࠬࡐ࠱ࡦ㧔․ߦ࠻ࡠ࠻ࡦࠬࡐ࠱ࡦ㧕㗔ၞߦ↱᧪ߒߡߚ߹ޕ ߚࠄࠇߎޔዊಽሶ RNA ߪ Dicer2 ଐሽ⊛ߦ↥↢ߐࠇࠆߎߣࠍࠄ߆ߦߒߚޔߦࠄߐޕDicer2 ߩᄌ⇣ߢߪߎࠇࠄዊಽሶ RNA ߩ↥↢߇ࠄࠇߕ৻ޔᣇޔᐞߟ߆ߩ࠻ࡠ࠻ࡦࠬࡐ࠱ ࡦߩ⊒߇ߒߡߚޕએߩ⚿ᨐࠍ✚วߔࠆߣޔAGO2 ߪฦ⒳࠻ࡦࠬࡐ࠱ࡦߦ↱ ᧪ߔࠆౝᕈ siRNA ߣ⋧↪ߒߡ߅ࠅࠄࠇߎ߽߆ߒޔౝᕈ siRNA ߪ⚦⢩ߦ߅ߡ ᐞߟ߆ߩ࠻ࡠ࠻ࡦࠬࡐ࠱ࡦߩ⊒ࠍᛥߒߡࠆߎߣ߇ࠄ߆ߣߥߞߚޕdFMR1 ߪ ߎߩ AGO2 ߣ⋧↪ߒߡࠆߎߣߦߥࠆ⑳ޔࠄ߆ߣߎߩࠄࠇߎޕ㆐ߪ⣀ᒙ X ∝⟲⊒ ∝ߦ߅ߌࠆࡦ࠱ࡐࠬࡦ࠻ޟ⺑ࠍޠឭ໒ߔࠆߦ⥋ߞߚߩߎޕ⺑ߪࡦ࠱ࡐࠬࡦ࠻ޔ ߪ⚻೨㚟⚦⢩ࠍ⚦⢩ߢߎࠇ߹ߢ⠨߃ࠄࠇߡߚએߦᵴ⊒ߦォ౮ߐࠇߡ߅ ࠅࠆޔߡߞ߇ߚߒޔ㗫ᐲߢࠥࡁࡓߩࠆ㗔ၞߦォ⒖ᝌߐࠇࠆน⢻ᕈ߇ࠆޕ AGO2/FMR1 ⶄวߪߎࠇࠄ⚦⢩ߦ߅ߌࠆ࠻ࡦࠬࡐ࠱ࡦߩォ⒖ࠍᛥߒߡ߅ࠅߚߒޔ ߇ߞߡⶄߩߎޔวߩᯏ⢻⇣Ᏹ߇࠻ࡦࠬࡐ࠱ࡦߩ⚻ޔ߫߃ߣߚޔ㑐ㅪㆮવሶ߳ォ⒖ ᝌࠍᄌൻߐߖ⚿ߩߘޔᨐ⊛⇣․⚻ࠆޔㆮવሶߩㆊ⊒߹ߚߪㆊዋ⊒ࠍߊޔ ߣ߁߽ߩߢࠆޕ ⸵․ޣ㗿ᢙߩታ❣ޤ ߥߒޕ ࠥࡁࡓࡀ࠶࠻ࡢࠢࡊࡠࠫࠚࠢ࠻ߩ ⺖㗴ߩႎ๔ ࡊࡠࠣࡓฬ ⺖㗴ߩಽ㘃 ⺖ 㗴 ฬ 㧔⧷૬⸥㧕 㧔㧝㧕ࠥࡁࡓᯏ⢻ᖱႎߩ⸃ᨆ 㧔㧞㧕ࡅ࠻ࠥࡁࡓࡀ࠶࠻ࡢࠢ ࡊ࠶࠻ࡈࠜࡓߩ᭴▽ 㧔㧟㧕ᰴઍࠥࡁࡓ⸃ᨆᛛⴚߩ㐿⊒ 㧔㧠㧕↢ᯏ⢻ߩ⸃ᨆ 㧔㧡㧕േ⊛ࡀ࠶࠻ࡢࠢ⸃ᨆᛛⴚ㐿⊒ 㧔㧝㧕ਛᩭᯏ㑐 㧔㧞㧕ᜰቯ⺖㗴 㧔㧟㧕⺖㗴 ↢ᯏ⢻ߦ߅ߌࠆォ౮࿃ሶߩᯏ⢻ࡀ࠶࠻ࡢࠢߣ∔ᖚ 㧔Functional Networks of Transcription Factors in Individual Biological Function and Related Diseases㧕 ઍ⎇ⓥ⠪ฬ 㜞ᯅ ᥓ 㧔ᚲዻᯏ㑐⡯ฬ㧕 㧔࿖┙ᄢቇᴺੱ╳ᵄᄢቇᢎ㧕 ᐕᐲ⎇ⓥ⾌ 㧝㧢ᐕᐲ 㧝㧣ᐕᐲ 㧝㧤ᐕᐲ 㧝㧥ᐕᐲ 㧞㧜ᐕᐲ ว ⸘ 㧔ජ㧕 ⎇ⓥ⠪ฬ ᚲዻᯏ㑐ㇱዪ⡯ ኾ㐷ಽ㊁ ╳ᵄᄢቇ ᄢቇ㒮ੱ㑆✚ว⑼ቇ⎇ⓥ⑼ᢎ ⊒↢Ꮏቇ ⎇ ઍᯏ㑐ڏ㜞ᯅ ᥓ ự↰ ℂੱ ╳ᵄᄢቇ ᄢቇ㒮ੱ㑆✚ว⑼ቇ⎇ⓥ⑼⎇ⓥຬಽሶ↢‛ቇ ⓥ ڏട⮮ శ ╳ᵄᄢቇ ᄢቇ㒮ੱ㑆✚ว⑼ቇ⎇ⓥ⑼ᢎ ታ㛎∛ℂቇ ⚵ ❱ દ᧲ ㅴ ╳ᵄᄢቇ ᄢቇ㒮ੱ㑆✚ว⑼ቇ⎇ⓥ⑼ಎᢎಽሶ↢‛ቇ ࿑ ╳ᵄᄢቇ ᄢቇ㒮ੱ㑆✚ว⑼ቇ⎇ⓥ⑼ᢎ ಽሶ↢‛ቇ ڏ⍹ ବテ ⎇ޣⓥ⋡⊛ޤ 㜞╬↢‛ߩ⊒↢ࠍᜂ߁ォ౮࿃ሶ⟲ߪޔ㘃ૃߩ↢ൻቇ⊛᭴ㅧࠍᜬߟಽሶ⟲߆ࠄߥࠆࡈ ࠔࡒࠍᒻᚑߒߡࠆߩࠄࠇߎޔߚ߹ޕォ౮࿃ሶ⟲߇ᯏ⢻ߔࠆߚߦߪޔォ౮࿃ሶߣߘ ߩᵴᕈࠍ⺞▵ߔࠆࠪࠣ࠽࡞ಽሶ⟲߇৻ߣߥߞߡᯏ⢻⊛ࡀ࠶࠻ࡢࠢࠍᒻᚑߒߡࠆࠥޕ ࡁࡓᖱႎߩᵴ↪ߩߚߦߪࡓࡁࠥޔߦಽᢔߒߡࠆㆮવሶ⟲ࠍߎߩᯏ⢻⊛ࡀ࠶࠻ࡢࠢ ࠍනߣߒߡࠄ߃ࠆߎߣ߇ᔅⷐߢߚߞߥ⇣ߊోߡߞࠃߦࠇߘޔㆮવሶ߇หߓ∔ᖚߩේ࿃ ߦߥࠆߎߣ߽ℂ⸃ߔࠆߎߣ߇น⢻ߣߥࠆޔߪߢ⺧↳ᧄޕ᭽ߥޘㆮવሶᡷᄌᣇᴺ߇↪น⢻ ߥࡑ࠙ࠬࠍࡕ࠺࡞↢‛ߣߒߡᤨޔⓨ㑆⊛ߦಽߌࠄࠇࠆォ౮࿃ሶ⟲ߣࠪࠣ࠽࡞વ㆐ಽሶ ⟲ࠍޔ↢ᯏ⢻ߦ㑐ਈߔࠆᯏ⢻⊛ࡀ࠶࠻ࡢࠢߣߒߡหቯߒ⇣ߩࠄࠇߘޔᏱߦࠃߞߡ ⊒↢ߔࠆဳ㧔∔ᖚࡕ࠺࡞㧕ߦߟߡ⸃ᨆߔࠆޕ ⺖ޣ㗴ߩⷐޤ ᧄ↳⺧ߢߪᤨޔߡߒߣ‛↢࡞࠺ࡕࠍࠬ࠙ࡑޔⓨ㑆⊛ߦಽߌࠄࠇࠆォ౮࿃ሶ⟲ߣࠪࠣ ࠽࡞વ㆐ಽሶ⟲ࠍޔ↢ᯏ⢻ߦ㑐ਈߔࠆᯏ⢻⊛ࡀ࠶࠻ࡢࠢߣߒߡหቯߒߩࠄࠇߘޔ ⇣Ᏹߦࠃߞߡ⊒↢ߔࠆဳ㧔∔ᖚࡕ࠺࡞㧕ߦߟߡ⸃ᨆߔࠆ⎇ᧄߦ․ޕⓥߢߪ⋧ޔߦ ᯏ⢻ࠍಽᜂ߅ࠃ߮⋧ߔࠆࡈࠔࡒࠍᒻᚑߔࠆォ౮࿃ሶ㑆ࡀ࠶࠻ࡢࠢ㧔㧝ᰴࡀ࠶࠻ࡢ ࠢ㧕ߣ⋧ߩ⾰ࠢࡄࡦ࠲ޔ↪㧔‛ℂ⊛ળว߿ࡦ㉄ൻ㧕߿ᮡ⊛⚿ว㈩ߩ┹ว ߦࠃߞߡᒻᚑߐࠇࠆォ౮࿃ሶ⟲㑆ࡀ࠶࠻ࡢࠢ㧔㧞ᰴࡀ࠶࠻ࡢࠢ㧕ߩ⊒↢ߦ߅ߌࠆ ᯏ⢻ࠍࠄ߆ߦߔࠆߚߦ⋧ޔߦࡀ࠶࠻ࡢࠢࠍᒻᚑߔࠆ6)($45OCFࡈࠔࡒޔ5JP ࡈࠔࡒ߅ࠃ߮D<KRဳォ౮࿃ሶߢࠆ#6(ߣ.CTIG/CHࡈࠔࡒߦߟߡޔ ࡌ࡞ߢ⸃ᨆࠍⴕ߁ޕ ޣᐔᚑ㧞㧜ᐕ㧤ᧃ߹ߢߩ⎇ⓥᚑᨐޤ #.-&#ࡁ࠶ࠢࠗࡦࡑ࠙ࠬ▤ⴊޔౝ⊹⚦⢩․⇣⊛5OCF5OCF࠳ࡉ࡞ࡁ࠶ࠢࠕ࠙࠻ࡑ ࠙ࠬޔౝ⊹⚦⢩․⇣⊛#.-ࡁ࠶ࠢࠕ࠙࠻ࡑ࠙ࠬࠍߒޔ5OCF5OCFࠍߔࠆ6)(Eࠪ ࠣ࠽࡞ߩⴊ▤ᣂ↢ߦ߅ߌࠆᯏ⢻ࠍࠄ߆ߦߒߚޔߦࠄߐޕ6)(E$/2ࠪࠣ࠽࡞ߦࠃࠆⴊ▤ᣂ ↢ߦ߅ߌࠆ'ࠍਛᔃߣߒߚォ౮࿃ሶࡀ࠶࠻ࡢࠢࠍࠄ߆ߦߒߚޕ 5JPߣ#6(ࡈࠔࡒォ౮࿃ሶߩᄌ⇣ࡑ࠙ࠬࠍ↪ߡޔ5JP߇$/2ଐሽ⊛ߥ⢽⢌⚦⢩ ಽൻߦ㊀ⷐߥᓎഀࠍᨐߚߔߎߣߡߒߘޔ#6(߇߇ࠎᛥ࿃ሶߣߒߡ↪ߔࠆߎߣࠍࠄ ߆ߦߒߚߦࠄߐޕ#6(ࡈࠔࡒォ౮࿃ሶ߇ⴕޔേᓮ߿⢽⢌⚦⢩ಽൻߦ߽ޔ㊀ⷐߥᓎഀ ࠍᨐߚߔߎߣࠍޔࠄ߆ߦߒߟߟࠆޕ ᄢ/CH⟲ォ౮࿃ሶߩᄌ⇣ࡑ࠙ࠬࠍ↪ߡޔ/CH#߇ᚑߩࡑ࠙ࠬߦ߅ߡ⤳⤟ޔE⚦⢩ߦ߅ ߌࠆࠗࡦࠪࡘࡦߩォ౮߮ಽᴲߦᔅ㗇ߩォ౮࿃ሶߢࠆߎߣࠍࠄ߆ߦߒߚߚ߹ޕหߓ ᄢ/CH⟲ォ౮࿃ሶߢࠆ/CH$߇ޔ⢝↢ᦼߩ⤟⤳ౝಽᴲ⚦⢩ߢ⊒ߒߡ߅ࠅޔ/CH$ߩᰳ៊ࡑ࠙ ࠬߢߪޔ⢝↢ᦼߩ⤟⤳D߅ࠃ߮E⚦⢩ߩᢙ߇⪺ߒߊᷫዋߔࠆߎߣࠄ߆ߦߒߚޔߦࠄߐޕ/CH# ߅ࠃ߮/CH$ߩੑ㊀ᰳ៊ࡑ࠙ࠬߢߪޔE⚦⢩ߦ߅ߌࠆࠗࡦࠪࡘࡦߩォ౮߇߶ߣࠎߤ⺃ዉߐࠇ ߥߎߣࠍࠄ߆ߦߒߚ⚿ߩࠄࠇߎޕᨐ߆ࠄޔᄢ/CH⟲ォ౮࿃ሶߪ⤟⤳ߩౝಽᴲ⚦⢩ߩᦨ⚳ ಽൻߦᔅ㗇ߩォ౮࿃ሶߢࠆߎߣࠍࠄ߆ߦߒߚޕ ৻ᣇ∉ޔᜂᒰ⚦⢩ߩࡑࠢࡠࡈࠔࠫߩᯏ⢻⊒ߦ/CH$߇ᔅ㗇ߢࠆߎߣࠍࠄ߆ߦߒ ߚ߇ޔ/CH$ᰳ៊ߩࡑࠢࡠࡈࠔࠫߢߪޔ᛫ࠕࡐ࠻ࠪࠬ↪ࠍߔࠆ#+/ߩ⊒⺃ዉ߇߅ߎ ࠄߥߚޔ᭽ߥޘೝỗߦኻߒߡࠕࡐ࠻ࠪࠬ߇⺃ዉߐࠇ߿ߔߎߣࠍࠄ߆ߦߒߚ․ޕ ߦേ⣂⎬ൻ∛Ꮍߢᒻᚑߐࠇࠆᵃᴜ⚦⢩߇ᒻᚑߐࠇߕޔേ⣂⎬ൻ∛Ꮍ߇ᒻᚑߐࠇߦߊߎߣ ࠍࠄ߆ߦߒߚߦࠄߐޕE/CHᰳ៊ࡑࠢࡠࡈࠔࠫߦ߅ߡ߽ޔㅧⴊᡰᜬ⢻ജ߇ᷫዋߒߡ ࠆߎߣࠍࠄ߆ߦߒߚߩࠫࠔࡈࡠࠢࡑߦ߁ࠃߩߎޕᯏ⢻⊒ߦޔᄢ/CH⟲ォ౮࿃ሶ߇ᔅ㗇 ߢࠆߎߣࠍ⸽ߒߟߟࠆޕ ޣ㧳㧺㧼ߣߩ㑐ㅪ㧳㧺㧼߳ߩ⽸₂ޤ 㨍㧕ォ౮ᓮߩ⸃ߦ㑐ㅪߔࠆ⎇ⓥᚑᨐ ᧄ⎇ⓥߢߒߚㆮવሶᡷᄌࡑ࠙ࠬࠍ↪ߡߩࠇߙࠇߘޔォ౮࿃ሶߪߚ߹ޔ㑐ㅪ࿃ሶߦ ࠃߞߡᓮߐࠇࠆォ౮ࡀ࠶࠻ࡢࠢࠍࠄ߆ߦߒߚޕ ⴊ▤ᣂ↢ߦ߅ߌࠆ5OCF5OCFࠍߔࠆ6)(Eࠪࠣ࠽࡞ߩᓎഀߩ⸃ 6)(E/$/2ࠪࠣ࠽࡞ߦࠃࠆⴊ▤ᣂ↢ࠍᓮߔࠆᣂߚߥォ౮࿃ሶࡀ࠶࠻ࡢࠢߩหቯ ⢽⢌⚦⢩ಽൻߣ߇ࠎ⊒∝ࠍᓮߔࠆᣂߚߥォ౮࿃ሶࡀ࠶࠻ࡢࠢߩหቯޕ ⤟⤳E⚦⢩ߩᯏ⢻⊒ߩࡀ࠶࠻ࡢࠢߩหቯޕ ࡑࠢࡠࡈࠔࠫᯏ⢻⊒ߩࡀ࠶࠻ࡢࠢߩ⸃ޕ 㨎㧕❑ゲ⎇ⓥ㧔߹ߚߪᮮゲ⎇ⓥ㧕߳ߩ⽸₂ߦ❬߇ࠆ⎇ⓥᚑᨐ ⢽⢌⚦⢩ಽൻߣ߇ࠎ⊒∝ߦ㑐ㅪߔࠆㆮવሶ⊒ࡀ࠶࠻ࡢࠢߩࠕࠗ⸃ᨆ࠺࠲ࠍข ᓧߒߚޕ ❑ゲ㑆ߩห⎇ⓥߣߒߡޔ㜞ᩉ࠴ࡓޔᵻේ࠴ࡓޔ࠴ࡓޔጟፒ࠴ࡓߦㆮવሶᡷ ᄌࡑ࠙ࠬࠍଏ⛎ߒߚޕ ᮮゲߩᨋ㦮࠴ࡓߦ/CH$ᰳ៊ࡑࠢࡠࡈࠔࠫߩࠕࠗ࠺࠲ࠍଏ⛎ߒߚޕ ޣᒰ⎇ⓥߦ㑐ߒߡᵴ↪ߒߚ⎇ⓥ࠺࠲࠰ࠬޤ ᮮゲ(#061/E&0#ENQPGENQPGU࠻ࡅޔE&0#ENQPGUޔ )02⛔ว࠺࠲ࡌࠬ ޣਥߥ⎇ⓥ⺰ᢥߣߘߩⷐޤ 0QFC&+VQJ59CVCPCDG;+PCOKVUW/&GPPNGT5+VQJ(-QKMG5&CPKGNRQWT &VGP&KLMG2CPF-CVQ/'.#%CRWVCVKXGRTQUVCVGECPEGTUWUEGRVKDKNKV[IGPG RTQFWEV RQVGPVKCVGU 6)(E5OCFKPFWEGF ITQYVJ CTTGUV QH RTQUVCVG EGNNU 1PEQIGPG )02⻢ㄉ 6)(Eߦࠃࠆᮡ⊛ㆮવሶߩォ౮ߦޔᩭ࠲ࡦࡄࠢ⾰'.#%߇㑐ਈߔࠆߎߣࠍ␜ߒߚޕ ,KP96CMCIK6-CPGUCUJK5-WTCJCUJK60QOWTC6*CTCFC,+UJKK55EJPWTTK EQPVTQNU$/2FGRGPFGPVCFKRQIGPGUKUXKCKPVGTCEVKQPYKVJ5OCFRTQVGKPU&GX%GNN )02⻢ㄉ 5JP-1ࡑ࠙ࠬࠍ↪ߡޔ5JP߇5OCFߣ⋧↪ߒޔ$/2ଐሽ⊛ߥ⢽⢌⚦⢩ಽൻߦ㊀ ⷐߥᓎഀࠍᨐߚߔߎߣࠍࠄ߆ߦߒߚޕ /CGMCYC65JKPCICYC65CPQ;5CMWOC60QOWTC50CICUCMK-/KMK;5CKVQ1JCTC (+PC\CYC,-QJPQ6;QMQVC,+UJKK54GFWEGFNGXGNUQH#6(RTGFKURQUGOKEG VQOCOOCT[VWOQTU/QN%GNN$KQN )02⻢ㄉ #6(ࡋ࠹ࡠᄌ⇣ࡑ࠙ࠬ߇㜞㗫ᐲߦ߇ࠎࠍ⊒∝ߒޔ#6(߇߇ࠎᛥ࿃ሶߣߒߡ ↪ߔࠆߎߣࠍࠄ߆ߦߒߚޕ /QTKIWEJK6*COCFC//QTKVQ06GTWPWOC6*CUGICYC-<JCPI%;QMQOK\Q6'UCMK 4-WTQFC';QJ--WFQ60CICVC/'PIGN,&;COCOQVQ/6CMCJCUJK5 /CH$KU GUUGPVKCNTGPCNFGXGNQROGPVCPF(GZRTGUUKQPKPOCETQRJCIG/QN%GNN$KQN )02⻢ㄉ /CH$ߪ⪉⣖ߩᒻᚑޔ⣢⤳ߩ♻ߩᒻᚑ߅ࠃ߮ࡑࠢࡠࡈࠔࠫߩᯏ⢻ಽൻߦᔅ㗇ߩォ ౮࿃ሶߢࠆߎߣࠍࠄ߆ߦߒߚޕ -CVQ65JKOCPQ*;COCOQVQ6;QMQQ6'PFQ;+UJKMCYC//CVW\CMC60CMCICYC ;;CJCIK06CMCJCUJK#5QPG*5W\WMK*6Q[QUJKOC**CUV[#*6CMCJCUJK5 )QOK*+\WOK6;COCFC0)TCPWRJKNKPKUCEVKXCVGFD[54'$2ECPFKPXQNXGFKP %GNN/GVCDQNKUO KORCKTGFKPUWNKPUGETGVKQPKPFKCDGVKEOKEG% /CH#߇⤟⤳Ǫ⚦⢩ߦ߅ߡࠗࡦࠪࡘࡦಽᴲ㗰☸ߩ⚦⢩⤑߳ߩ࠼࠶ࠠࡦࠣߦᔅⷐߥ )TCPWRJKNKPߩ⊒⺃ዉߦᔅ㗇ߢࠆߎߣࠍࠄ߆ߦߒߚߣหᤨߦޔ⢽⾰ઍ⻢ᓮォ౮ ࿃ሶߢࠆ54'$2E߽)TCPWRJKNKPߩ⊒ࠍ⺃ዉߔࠆߎߣࠍࠄ߆ߦߒߚޕ ⸵․ޣ㗿ᢙߩታ❣ޤ ޟㆮવሶᡷᄌߦࠃࠆᣂⷙ♧ዩ∛ࡕ࠺࡞ࡑ࠙ࠬߩ㐿⊒ޠ 㧔․㗿․ޔ㐿㧕 ࠥࡁࡓࡀ࠶࠻ࡢࠢࡊࡠࠫࠚࠢ࠻ߩ ⺖㗴ߩႎ๔ ⺖㗴ߩಽ㘃 㧔㧝㧕ࠥࡁࡓᯏ⢻ᖱႎߩ⸃ᨆ 㧔㧞㧕ࡅ࠻ࠥࡁࡓࡀ࠶࠻ࡢࠢ ࡊ࠶࠻ࡈࠜࡓߩ᭴▽ 㧔㧟㧕ᰴઍࠥࡁࡓ⸃ᨆᛛⴚߩ㐿⊒ 㧔㧠㧕↢ᯏ⢻ߩ⸃ᨆ 㧔㧡㧕േ⊛ࡀ࠶࠻ࡢࠢ⸃ᨆᛛⴚ㐿⊒ 㧔㧝㧕ਛᩭᯏ㑐 㧔㧞㧕ᜰቯ⺖㗴 㧔㧟㧕⺖㗴 ⺖ 㗴 ฬ 㧔⧷૬⸥㧕 ㆇേེߩᒻᚑ⛽ᜬ⠧ൻߦ㑐ࠊࠆㆮવሶᓮࡀ࠶࠻ࡢࠢߩ⸃ 㧔Gene Control Networks Associated with the Development, Maintenance, and Aging of the Locomotor System㧕 ࡊࡠࠣࡓฬ ઍ⎇ⓥ⠪ฬ 㜞ᩉ ᐢ 㧔ᚲዻᯏ㑐⡯ฬ㧕㧔࿖┙ᄢቇᴺੱ᧲੩ක⑼ᱤ⑼ᄢቇᢎ㧕 ᐕᐲ⎇ⓥ⾌ 㧝㧢ᐕᐲ 㧝㧣ᐕᐲ 㧝㧤ᐕᐲ 㧝㧥ᐕᐲ 㧞㧜ᐕᐲ ว ⸘ 㧔ජ㧕 ⎇ⓥ⠪ฬ ᚲዻᯏ㑐ㇱዪ⡯ ኾ㐷ಽ㊁ ⎇ ઍᯏ㑐 ڏ㜞ᩉ ᐢ ᧲੩ක⑼ᱤ⑼ᄢቇಽሶᖱႎવ㆐ቇᢎ 㛽∉ቇᢛᒻᄖ⑼ቇ ◉ේ ᱜᶈ ᧲੩ක⑼ᱤ⑼ᄢቇಽሶᖱႎવ㆐ቇഥᢎ 㛽∉ቇ↢ൻቇ ⓥ ⚵ ਛፉ ♿ ᧲੩ක⑼ᱤ⑼ᄢቇಽሶᖱႎવ㆐ቇഥᢎ 㛽∉ቇಽሶ↢‛ቇ ❱ಽᜂᯏ㑐 ڏ㧔ઍ⎇ⓥ⠪㧕 ࿑ 㧔ಽᜂ⎇ⓥ⠪㧕 ⎇ޣⓥ⋡⊛ޤ 㜞㦂ൻ␠ળ߇ㅴዷߔࠆਛ↢ޔᵴߩ⾰ߦ⋥⚿ߔࠆㆇേེ∔ᖚߩసߪක≮ߩᄢ߈ߥ⺖㗴 ߢࠆᧄޕᬺോ⺖㗴ߢߪޔ㛽㑐▵ࠍ᭴ᚑߔࠆ⎕㛽⚦⢩߿㛽⧘⚦⢩ߥߤࠍਥߥ⎇ⓥߩኻ⽎ ߣߒ⸃ࡓ࠻ࡊࠢࠬࡦ࠻ޔᨆ߿ࡊࡠ࠹ࠝࡓ⸃ᨆߦࠃߞߡᓧࠄࠇࠆㆮવሶ⊒ᖱႎࠍ ߽ߣߦߒߡޔᮮゲ⎇ⓥߢᓧࠄࠇࠆᖱႎࠍㆇേེಽ㊁ߦ߅ߡᵴ↪ߒޔᒰ↢♽ߦ߅ߡ ⊒ߔࠆㆮવሶ⊒ᓮᯏ᭴ࠍࡀ࠶࠻ࡢࠢߣߒߡℂ⸃ߔࠆߎߣࠍ⋡⊛ߣߔࠆޔߚ߹ޕ ㆮવሶߩᯏ⢻⸃ᨆߦߚߞߡߪޔᮮゲ⎇ⓥ߆ࠄឭଏߐࠇࠆsiRNAޔcDNAߥߤߩ࠰ࠬ ࠍᵴ↪ߒߩߤߥࠬ࠙ࡑ࠻࠙ࠕࠢ࠶ࡁߪߦ⊛⚳ᦨޔㆮવቇ⊛ᚻᴺࠍ↪ߡࡌ࡞ߢߩ↢ ℂቇ⊛ߥᗧ⟵ߩ⸽ࠍផㅴߔࠆߎߣߢ∔ޔᖚᴦ≮ߦᓎ┙ߟಽሶࡔࠞ࠾࠭ࡓߩ⸃ࠍ⋡ᜰߔޕ ⺖ޣ㗴ߩⷐޤ 㛽ઍ⻢⚦⢩ߢࠆ⎕㛽⚦⢩ޔ㛽⧘⚦⢩ߩಽൻ߅ࠃ߮ᯏ⢻ߦ㑐ߔࠆᓮࡔࠞ࠾࠭ࡓࠍォ౮ ᓮࡀ࠶࠻ࡢࠢߩⷰὐ߆ࠄ⸃ߔࠆޕ⎕㛽⚦⢩߅ࠃ߮㛽⧘⚦⢩ಽൻᲑ㓏ߦ߅ߌࠆ⚻ᤨ⊛ ✂⟜⊛ㆮવሶ⊒ᖱႎ߿ࡊࡠ࠹ࠝࡓ⸃ᨆࠍታᣉߒޔಽൻߦߞߡ⊒߇ㅴ߹ߚߪᛥ ߐࠇࠆಽሶࠍหቯߔࠆޕหቯಽሶߩࡁ࠶ࠢࠕ࠙࠻ࡑ࠙ࠬߩ㛽ߩဳࠍ⸃ᨆߔࠆߎߣߢޔ ↢ᯏ⢻߳ߩ㑐ਈࠍ␜ߔߣߣ߽ߦ⸃࠲ࡕࡠࡊߥ⊛⟜✂ޔᨆ߿࠲ࡦࡄࠢ⾰㑆⋧⸃ᨆࠍ ታᣉߔࠆߎߣߢޔㆇേེ♽ߦ߅ߌࠆㆮવሶ⊒ᓮᯏ᭴ࡀ࠶࠻ࡢࠢߩ⸃ࠍⴕ߁ޕ ޣᐔᚑ㧞㧜ᐕ㧤ᧃ߹ߢߩ⎇ⓥᚑᨐޤ ߎࠇ߹ߢ㛽ઍ⻢ࠍᜂ߁⚦⢩ߢࠆ⎕㛽⚦⢩߮㛽⧘⚦⢩ߦ߅ߌࠆォ౮࿃ሶ NFATc1 ߩ㊀ⷐ ߥᓎഀࠍਛᔃߦޔ㛽ઍ⻢⚦⢩ߦ߅ߌࠆォ౮ᓮࡀ࠶࠻ࡢࠢᯏ᭴ࠍࠄ߆ߦߒߡ߈ߚޕ NFATc1 ߪ⎕㛽⚦⢩․⇣⊛ߥㆮવሶ⊒ࠍ⺃ዉߔࠆߎߣߢᚑᾫ⎕㛽⚦⢩߳ߣಽൻߐߖࠆࡑ ࠬ࠲ォ౮࿃ሶߣߒߡߊ߇ޔ⎕㛽⚦⢩ಽൻㆊ⒟ߢ⊒㊂߇ߔࠆೝỗ∉ฃኈ OSCAR ߽ޔNFATc1 ߩᮡ⊛ㆮવሶߣߒߡ PU.1 ߿ MITF ࠃࠅᚑࠆォ౮ⶄวߦࠃߞߡᓮߐ ࠇࠆߎߣࠍࠄ߆ߦߒߚޕOSCAR ߪࠞ࡞ࠪ࠙ࡓࠪࠣ࠽࡞ࠍߒߡ NFATc1 ࠍߐࠄߦᵴᕈൻ ߔࠆᱜߩࡈࠖ࠼ࡃ࠶ࠢ࡞ࡊᯏ᭴ࠍࠄ߆ߦߒߚ㧔 㧔J Biol Chem, 280:32905, 2005㧕ޕ ߹ߚ NFATc1 ߩ⎕㛽⚦⢩ߦ߅ߌࠆᯏ⢻ߪ⋧ޔหᕈߩ㜞ࡈࠔࡒಽሶߢࠆ NFATc2 ߦ ࠃߞߡઍఘߢ߈ߥޕNFATc1 ߅ࠃ߮ NFATc2 ߩࡊࡠࡕ࠲⸃ᨆࠃࠅߕࠇ߽ NFAT ⚿ว㈩ ࠍᜬߟ߇ޔNFATc1 ߩ․⇣⊛ߥ⥄ᏆჇᱺߪࠢࡠࡑ࠴ࡦࡕ࠺ࡦࠣ࿃ሶ߇ NFATc1 ㆮવሶߩ ࡊࡠࡕ࠲ߦ․⇣⊛ߦേຬߐࠇߚ⚿ᨐߦࠃࠆ߽ߩޔಽൻೋᦼߢߪޔNFATc2 ޔNFkB ࠃࠅ ᒻᚑߐࠇࠆォ౮࿃ሶⶄว߇ NFATc1 ߩೋᦼ⺃ዉߦ㑐ࠊࠅޔಽൻߩㅴⴕߦߞߡ NFATc1 ⥄ り߇ c-Fos ߣⶄวࠍᒻᚑߒߡ NFATc1 ࡊࡠࡕ࠲ߦ⚿วߒޔNFATc1 ߩ⥄ᏆჇᱺ߇↢ߓࠆ ߎߣࠍࠄ߆ߦߒߚ㧔 㧔J Exp Med, 202:1261, 2005㧕ޕ ⎕㛽⚦⢩ߦ߅ߌࠆ NFATc1 ߩᵴᕈൻߦߪࠞ࡞ࠪ࠙ࡓࠪࠣ࠽࡞߇ᔅ㗇ߢࠆ߇ࠪ࡞ࠞߩߎޔ ࠙ࡓࠪࠣ࠽࡞ߩᵴᕈൻߦᔅ㗇ߥࠠ࠽ߣߒߡ⸃ࡓ࠻ࡊࠢࠬࡦ࠻ޔᨆߦࠃࠅ⎕㛽⚦⢩ ߦ߅ߌࠆ⊒߇㜞ߎߣ߇್ߒߚ Tec ࡈࠔࡒ࠴ࡠࠪࡦࠠ࠽ࠍหቯߒߚߩࠄࠇߎޕ ㉂⚛߇⎕㛽⚦⢩ಽൻߦᔅ㗇ߢࠆߎߣࠍ⸽ߒߚޔߦࠄߐޕPPI ᖱႎ߆ࠄޔ⎕㛽⚦⢩ಽൻߦᔅ 㗇ߢࠆ RANK ߮ ITAM ࠕ࠳ࡊ࠲ળวᕈฃኈਅᵹߢᯏ⢻ߔࠆㆮવሶߩ࠺࠲ࠍ ߒޔ⎕㛽⚦⢩ߩ࠻ࡦࠬࠢࡊ࠻ࡓᖱႎߣߩ⛔วࠍⴕޔ⎕㛽⚦⢩ಽൻߦ㑐ࠊࠆ⚻ᤨ⊛ࠪ ࠣ࠽࡞ࡀ࠶࠻ࡢࠢࠍ᭴▽ߒߚ⚿ߩߘޕᨐޔ⎕㛽⚦⢩ಽൻߦᔅ㗇ߥ Tec ࡈࠔࡒࠠ࠽ ߣߘߩࠕ࠳ࡊ࠲࠲ࡦࡄࠢ⾰ߣߩ⎕㛽⚦⢩ߦ߅ߌࠆᣂߚߥⶄวߩ⸃ߒޔ⎕㛽⚦⢩ಽൻߩ ಽሶࡔࠞ࠾࠭ࡓߦᣂߚߥ⍮ࠍ߽ߚࠄߒߚ㧔Cell 132:794, 2008㧕৻ޕᣇ࡞࠽ࠣࠪࡓ࠙ࠪ࡞ࠞޔ ߪ calmodulin-dependent kinase 㧔CaMK㧕߅ࠃ߮ߘߩਅᵹߢᵴᕈൻߐࠇࠆォ౮࿃ሶ CREB ߽ᵴ ᕈൻߔࠆޕಽሶࡌ࡞ߢߩ⸃ᨆߦࠃࠅޔCaMK-CREB ⚻〝ߪ NFATc1 ⥄ᏆჇᱺߦᔅ㗇ߩ c-Fos ߩ⊒ࠍ⺃ዉߔࠆߎߣߢಽൻࠍᓮߒߡࠆޔCREB ߣ NFAT ߇ද⺞⊛ߦ⎕㛽⚦⢩․⇣⊛ ㆮવሶߩ⊒ࠍ⺃ዉߔࠆߎߣߢ㛽ๆᵴᕈ߽ᓮߔࠆߎߣࠍࠄ߆ߦߒߚߩߎޕ CaMK/CREB ⚻〝ߪޔಽൻߣᯏ⢻ߩੑጀᕈߦ⎕㛽⚦⢩ߩォ౮ᓮߦ㑐ࠊࠆߎߣ߇ࠄ߆ߦߥ ࠅߢࡓ࠙ࠪ࡞ࠞޔᓮߐࠇࠆੑߟߩォ౮࿃ሶ⚻〝ߩද⺞ߦࠃࠆォ౮ᓮࡀ࠶࠻ࡢࠢ߇⸃ 㧔Nat Med, 12:1410, 2006㧕 ޕ ߐࠇߚ㧔 એߩࠃ߁ߦޔNFATc1 ߪ⎕㛽⚦⢩ಽൻᯏ⢻ߦ㊀ⷐߢࠆߎߣࠍ⠨ᘦߔࠆߣޔNFATc1 ࠍ ᮡ⊛ߣߒߚᴦ≮ᴺ߇㑐▵࠙ࡑ࠴ߥߤߩ⎕㛽⚦⢩ᕈ㛽⎕უߦലߢࠆߎߣࠍ␜ໂߒߡ ࠆ߇ޔሽߩ᛫࠙ࡑ࠴⮎ߦࠃࠆ㑐▵࠙ࡑ࠴ߩ㛽⎕უᛥᯏ᭴ߩᯏᐨߦߪਇߥὐ߇ᄙ ߒ߆ߒޕ᛫࠙ࡑ࠴⮎ߪ NFATc1 ⊒ࠍォ౮ࡌ࡞ߢᛥߒޔ⎕㛽⚦⢩ಽൻࠍᛥߔࠆߎ ߣࠍࠄ߆ߦߒޔNFATc1 ߩォ౮ࡌ࡞ߢߩ⊒ߦ↪ὐࠍߔࠆ⮎߇⎕㛽⚦⢩ᕈ㛽⎕უ 㧔Mod Rheumatol, 12:12, 2007㧕ޕ ∔ᖚߦ↪ߢࠆߎߣࠍታ⸽ߒߚ㧔 ⎕㛽⚦⢩ಽൻ࿃ሶ RANKL ߩ⊒⺃ዉߪޔ⎕㛽⚦⢩ಽൻᡰᜬ⚦⢩ߦࠃࠆ⎕㛽⚦⢩ᓮߦ߅ ߌࠆ㊀ⷐߥᓮࡐࠗࡦ࠻ߢࠆޕἻ∝ᕈ㛽⎕უߩ∛ᘒߦ߅ߡߪޔT ⚦⢩߇⎕㛽⚦⢩ಽൻࠍ ଦㅴߔࠆ߇ޔIL-17 ↥↢ᕈ Th ⚦⢩㧔Th17 ⚦⢩㧕߇㛽⧘⚦⢩ߦ߅ߌࠆ⎕㛽⚦⢩ಽൻ࿃ሶ RANKL ㆮવሶߩ⊒ࠍ⺃ዉߔࠆߎߣߢޔ⎕㛽⚦⢩ಽൻࠍଦㅴߔࠆࡔࠞ࠾࠭ࡓࠍࠄ߆ߦߒߚ㧔J Exp Med, 202: 2673, 2006㧕 ޕ ߹ߚޔἻ∝ᕈࠨࠗ࠻ࠞࠗࡦߩ߭ߣߟ TNFD߽⎕㛽⚦⢩ಽൻࠍଦㅴߔࠆߥ࠼ࠗࡢࡓࡁࠥޕㆮ વሶ⊒⸃ᨆࠍⴕߞߚ⚿ᨐޔTNFDߪೝỗࠪࠣ࠽࡞ࠍ⺃ዉߔࠆ∉ฃኈߣߘߩࠟࡦ࠼ ߩ⊒ㅴࠍߒߡNFATc1ߩᵴᕈࠍჇᒝߒޔ⎕㛽⚦⢩ಽൻࠍᒝജߦଦㅴߒߡࠆߎߣࠍ⸃ ߒߚ㧔Proc Natl Acad Sci USA 104:11394, 2007㧕ޕ ォ౮࿃ሶNFATߪ⎕㛽⚦⢩ߩߺߥࠄߕ㛽⧘⚦⢩ߢ߽㊀ⷐߥᓎഀࠍᨐߚߒߡࠆߎߣࠍ⸃ ߒߚޕNFATߩᒝജߥ㒖ኂ⮎ߢࠆFK506ߪޔ⎕㛽⚦⢩ಽൻࠍ㗼⪺ߦᛥߔࠆ߫߆ࠅߢߥߊޔ 㛽⧘⚦⢩ߦࠃࠆ㛽ᒻᚑ߽ᛥߔࠆߎߣࠍߛߒߚޕNFATߪ㛽⧘⚦⢩ಽൻߩᔅ㗇ォ౮࿃ሶ Osterixߣද⺞⊛ߦ㛽⧘⚦⢩․⇣⊛ㆮવሶ⟲ߩ⊒ࠍᓮߒߡߚޕNFATォ౮࿃ሶࡀ࠶࠻ࡢ ࠢߩ㛽⧘⚦⢩ߦ߅ߌࠆ㊀ⷐᕈߦട߃ޔNFAT߇⚦⢩⒳․⇣⊛ߦᮡ⊛ㆮવሶࠍࠆࡔࠞ࠾࠭ࡓ ߣߒߡޔNFATࠍਛᔃߣߒߚォ౮࿃ሶⶄวߩ㆑ߦࠆߎߣ߇␜ໂߐࠇߚ㧔Nat Med, 11:880, 2005㧕ߦࠄߐޕ㛽⧘⚦⢩ߩಽൻ߮ᯏ⢻ࠍᓮߔࠆォ౮࿃ሶࠍหቯߔࠆ⋡⊛ߢޔ1480ォ౮࿃ ሶߩ㛽⧘⚦⢩ߦ߅ߌࠆ✂⟜⊛ߥ⊒⸃ᨆࠍⴕߞߚ⚿ᨐޔᭂߡ㗼⪺ߥ⊒⺃ዉࠍ␜ߔォ౮࿃ ሶߣߒߡc-Mafࠍหቯߒߚߩߎޕc-Mafߪ㛽⧘⚦⢩ߩಽൻߣߣ߽ߦ⊒߇ㅴߒޔ㛽⧘⚦⢩ߦ ߅ߌࠆᯏ⢻߇੍ᗐߐࠇߚޕc-Mafߩ㛽ᒻᚑߦኻߔࠆ↢ࡌ࡞ߢߩ㊀ⷐᕈࠍᬌ⸛ߔࠆߚޔ c-Mafࡁ࠶ࠢࠕ࠙࠻ࡑ࠙ࠬࠍ⸃ᨆߒߚߣߎࠈޔ㛽ᒻᚑ߇ૐਅߒߡࠆߎߣ߇್ߒߚޕc-Maf ࡁ࠶ࠢࠕ࠙࠻ࡑ࠙ࠬ↱᧪ߩ㛽⧘⚦⢩ࠍ↪ߡ✂⟜⊛ㆮવሶ⊒ࠍ⸃ᨆߒߚ⚿ᨐޔc-Mafߪ㛽⧘ ⚦⢩․⇣⊛ߥㆮવሶ⊒ߦ㊀ⷐߢࠅޔbglap1ߦኻߒߡߪRunx2ߣද⺞⊛ߦ↪ߔࠆߎߣߢ⊒ ࠍᱜߦᓮߔࠆߎߣ߇ࠄ߆ߣߥߞߚ৻ޕᣇޔ㛳ߚߎߣߦޔc-Mafࡁ࠶ࠢࠕ࠙࠻⚦⢩ߪ⢽ ⢌⚦⢩ಽൻ߇ㅴߒߡߚޕ㛽⧘⚦⢩ߣ⢽⢌⚦⢩߳ߩಽൻ⢻ࠍߔࠆ⚦⢩ᩣߦኻߒߡc-Maf ߩㆊ⊒ࠍ⹜ߺߚ⚿ᨐޔc-Mafߪ⢽⢌⚦⢩ಽൻࠍᛥߔࠆᯏ⢻ࠍ߽ߟߎߣ߇␜ߐࠇߚޕᛥ ᯏ᭴ߩ⚦ߥ⸃ᨆߦࠃߞߡޔc-Mafߪ⢽⢌⚦⢩ಽൻߦ㊀ⷐߥCebpdߩォ౮ᵴᕈࠍ⽶ߦᓮߔࠆ ߎߣ߇ࠄ߆ߣߥߞߚᧄޕᚑᨐߦࠃߞߡޔc-Maf߇Runx2߿Cebpdߩᵴᕈࠍ⺞▵ߔࠆߎߣߢޔ 㛽⧘⢽⢌⚦⢩ಽൻߩㆇቯߦ㑐ਈߔࠆߎߣ߇␜ໂߐࠇߚ㧔⺰ޔᢥᛩⓂਛ㧕ޕ ߎߩઁޔ⎕㛽⚦⢩ߦ․⇣⊛ߦ⊒ߒޔ㛽ࠍಽ⸃ߔࠆ㉂⚛ߣ⠨߃ࠄࠇߡ߈ߚࠞ࠹ࡊࠪࡦ K ߩ ᣂߚߥᯏ⢻ߦߟߡࠞ࠹ࡊࠪࡦKߩࡁ࠶ࠢࠕ࠙࠻ࡑ࠙ࠬࠍ↪ߡߒߚ㧔Science 319: 624, 2008㧕ࡦࠪࡊ࠹ࠞߩߎޕKߪޔ⎕㛽⚦⢩ߛߌߢߥߊ᮸⁁⚦⢩ߦ߅ߡ߽⊒ߒߡ߅ࠅޔCpG ೝỗߦᔕ╵ߒߚࠨࠗ࠻ࠞࠗࡦߩ⊒ᓮߦ㑐ਈߒߡࠆߎߣ߽ࠄ߆ߦߒߚ⚿ߩߎޕᨐߪߎ ࠇ߹ߢ⎕㛽⚦⢩․⇣⊛ߣ⠨߃ࠄࠇߡߚࡊࡠ࠹ࠕ߇ޔ᮸⁁⚦⢩ߢ߈ߩ∉ޔᵴᕈൻߦ ㊀ⷐߥᓎഀࠍᜂ߁ߎߣࠍ␜ߒߡࠆޕ એߢ߹ࠇߎޔ⎕㛽⚦⢩㛽⧘⚦⢩ࠍਛᔃߦߘߩಽൻᲑ㓏ߦ߅ߌࠆォ౮ᓮࡔࠞ࠾࠭ࡓࠍ ࠄ߆ߦߒޔ㛽☻㝃∝ޔᄌᒻᕈ㑐▵∝ޔ㑐▵࠙ࡑ࠴ޔᱤ∛ޔవᄤᕈ㛽♽⛔∔ᖚߥߤߩ⒳ޘ ߩㆇേེ∔ᖚᴦ≮߳ߩォ౮ᓮࡀ࠶࠻ࡢࠢߦၮߠߚಽሶၮ⋚ࠍ⏕┙ߒߡ߈ߚޕ ޣ㧳㧺㧼ߣߩ㑐ㅪ㧳㧺㧼߳ߩ⽸₂ޤ 㨍㧕ォ౮ᓮߩ⸃ߦ㑐ㅪߔࠆ⎇ⓥᚑᨐ ⎕㛽⚦⢩ߦ߅ߌࠆ NFATc1 ߩᮡ⊛ㆮવሶߣߒߡหቯߐࠇߚ∉ฃኈ OSCAR ߿⎕㛽⚦⢩ ․⇣⊛ߥ TRAP ߪޔPU.1 ߅ࠃ߮ MITF ߇ NFATc1 ߣ⋧ਸ਼⊛ߦߡ OSCAR ࡊࡠࡕ࠲ߩ ᵴᕈࠍߍߡࠆߎߣࠍࠄ߆ߦߒߚ㧔J Biol Chem, 280:32905, 2005㧕 ߩߎޔߚ߹ޕNFATc1 ㆮવሶߩ․⇣ᕈߪޔNFkBޔc-Fos ߿ NFATc2 ߥߤߩォ౮࿃ሶߦࠃࠆද⺞⊛ߥ⊒ᓮᯏ᭴߅ ࠃ߮ࠛࡇࠫࠚࡀ࠹ࠖ࠶ࠢߥࠢࡠࡑ࠴ࡦᓮߦଐሽߒߚㆮવሶᓮࡔࠞ࠾࠭ࡓߩ㆑ߦࠃߞ ߡ㆐ᚑߐࠇߡࠆߎߣ߇ࠄ߆ߣߥߞߚ㧔J Exp Med, 202:1261, 2005㧕 ߦࠄߐޕCaMK/CREB ⚻〝߽ NFATc1 ߅ࠃ߮ c-Fos ߩ⊒⺃ዉߦ㑐ਈߒޔ⎕㛽⚦⢩ಽൻߦ㊀ⷐߥᓎഀࠍᜂߞߡࠆ ޔಽൻᓟᦼߢߪ NFATc1 ߣද⺞⊛ߦ⎕㛽⚦⢩․⇣⊛ㆮવሶߩ⊒ࠍᓮߒߡࠆߎߣࠍ⸃ ߒߚ㧔Nat Med, 12:1410, 2006㧕 ޕNFATc1 ߩᵴᕈൻߔࠆ࠴ࡠࠪࡦࠠ࠽ߣߒߡ Tec ࡈࠔࡒ ࠠ࠽߇ᔅ㗇ߢࠆߎߣࠍߔߣߣ߽ߦޔPPI ᖱႎߣㆮવሶ⊒ᖱႎࠍⲢวߒߚ࠺ ࠲ࠍ↪ߒߡޔTec ࡈࠔࡒࠠ࠽ߣߘߩࠕ࠳ࡊ࠲࠲ࡦࡄࠢ⾰ߣߩ⎕㛽⚦⢩ߦ߅ߌ ࠆᣂߚߥⶄวߩ⸃ߒޔ⎕㛽⚦⢩ಽൻߩಽሶࡔࠞ࠾࠭ࡓߦᣂߚߥ⍮ࠍ߽ߚࠄߒߚ㧔Cell 132 794, 2008㧕ߦࠄߐޕἻ∝ᕈ㛽⎕უߦ߅ߌࠆ⎕㛽⚦⢩ߩಽൻଦㅴߪޔTh17 ⚦⢩߆ࠄ↥↢ߐ ࠇࠆ IL-17 ߇㛽⧘⚦⢩ߩ RANKL ㆮવሶߩ⊒ࠍᓮߔࠆߎߣߢ߽ߚࠄߐࠇࠆߎߣ߇ࠄ߆ ߣߥߞߚ㧔J Exp Med, 202: 2673, 2006㧕ޕTNFD߽Ἳ∝ⅣႺਅߦ߅ߡ⎕㛽⚦⢩ࠍଦㅴߔࠆ߇ޔ TNFDሽਅߦ߅ߌࠆ࠻ࡦࠬࠢࡊ࠻ࡓ⸃ᨆࠍⴕߞߚߣߎࠈޔ⎕㛽⚦⢩ಽൻߩೝỗࠪ ࠣ࠽࡞ࠍᜂ߁∉ฃኈߩ৻ߟߢࠆ PIRA ߅ࠃ߮ߘߩࠟࡦ࠼ߢࠆ MHC Class I ߩ⊒ ߇ㅴߒߡࠆߎߣࠍ⓭߈ᱛޔTNFDߦࠃࠆ⎕㛽⚦⢩ߩಽൻଦㅴലᨐࠍ⸃ߒߚ㧔PNAS 104, 11394, 2007㧕 ߚ߹ޕ᛫࠙ࡑ࠴⮎ߪ⎕㛽⚦⢩೨㚟⚦⢩ߦ߅ߡ NFATc1 ߩ⊒ࠍᛥߔࠆ ߎߣߢޔ⎕㛽⚦⢩ಽൻࠍᛥߔࠆߎߣࠍ␜ߒޔNFATc1 ⊒ࠍᓮߔࠆ⮎߇⎕㛽⚦⢩ߦࠃ ࠆ㛽⎕უߦ↪ߢࠆߎߣࠍ␜ߒߚ㧔Modern Rheumatology, 12:12, 2007㧕ߩࠄࠇߎޕᚑᨐߪޔ GNP ߩォ౮ᓮࡀ࠶࠻ࡢࠢߩ৻┵ࠍ⸃ߒߡᣂߚߥ⍮ࠍ߽ߚࠄߒޔォ౮࿃ሶߩᓮ߇∔ ᖚᴦ≮ߩഃߦ߽↪ߢࠆߎߣࠍ␜ߔ߽ߩߢࠆޕ ৻ᣇޔ㛽⧘⚦⢩ߦ߅ߡ߽ NFAT ߪ㊀ⷐߥᓎഀࠍᨐߚߒߡ߅ࠅޔNFATc1 ߪ Osterix ߣ⚿ว ߒߡ㛽⧘⚦⢩․⇣⊛ㆮવሶߩ⊒ᓮߦ㑐ਈߒߡࠆߎߣࠍࠄ߆ߦߒߚ㧔Nat Med, 11:880, 2005㧕 ޔઁߩߎޕォ౮࿃ሶ c-Maf ߪ㛽⧘⚦⢩ಽൻߦ㊀ⷐߥ Runx2 ߣද⺞⊛ߦߡޔ㛽⧘⚦ ⢩․⇣⊛ㆮવሶߩ⊒ࠍᓮߔࠆߛߌߢߥߊޔ⢽⢌⚦⢩ಽൻࠍ CebpGߩ⊒ᛥࠍߒߡ⽶ ߦᓮߒߡࠆߎߣࠍࠄ߆ߦߒޔ㛽⧘⚦⢩ߦ߅ߌࠆォ౮ᓮࡔࠞ࠾࠭ࡓߩ৻┵ࠍ⸃ߒ ߚޕ 㨎㧕❑ゲ⎇ⓥ㧔߹ߚߪᮮゲ⎇ⓥ㧕߳ߩ⽸₂ߦ❬߇ࠆ⎇ⓥᚑᨐ ᘮᔕᄢቇᩉᎹᒄᔒඳ჻ߣߩㅪ៤ߦࠃߞߡޔ⎕㛽⚦⢩߮㛽⧘⚦⢩ߩ࠻ࡦࠬࠢࡊ࠻ ࡓᖱႎߣIVVᴺߦࠃࠆPPI࠺࠲ࠍ⛔วߒߚ࠰ࠬ㧔࠻ࡦࠬࠢࡊ࠻ࡓ-PPI࠺࠲㧕ߩ ᭴▽ࠍⴕޔ⎕⚦⢩ಽൻೋᦼᲑ㓏ߦ߅ߡc-FosߣNFNBߩද⺞⊛ߥ↪߇ࠄࠇࠆ৻ᣇޔಽൻ ㆊ⒟ߩਛᦼߢߪޔᣂࠄߚߦ⊒ߒߡ߈ߚTPRㆮવሶߩ⋧↪ߦޔNFNBߩ㑐ਈ߇ᒙ߹ࠅޔ ᦨ⚳ಽൻᲑ㓏ߦ߅ߡc-Fosࠍਛᔃߣߒߚォ౮࿃ሶࡀ࠶࠻ࡢࠢߦ⒖ⴕߒߡࠆߎߣ߇್ ߒߚޕ ࿖┙ᚑ⢒ක≮ࡦ࠲⎇ⓥᚲᵻේᒄ༹ඳ჻ߣߩห⎇ⓥߦࠃߞߡޔ⎕㛽⚦⢩ߦ߅ߌࠆ CaMK/CREB⚻〝ߩࡔࠞ࠾࠭ࡓߩ⸃ᨆࠍⴕߞߚ㧔Nat Med, 12:1410, 2006㧕ޕ ╳ᵄᄢቇ㜞ᯅᥓඳ჻ߣߩห⎇ⓥߦࠃߞߡޔc-Mafォ౮࿃ሶߩ㛽⸃ᨆࠍㅴߡ߅ࠅޔ㛽⧘ ⚦⢩ߦ߅ߌࠆc-Mafߩォ౮ᓮᯏ᭴ࠍ⸃ߒߚ㧔⺰ᢥᛩⓂਛ㧕ޕ ਛᩭᯏ㑐ߣߩห⎇ⓥߢޔ⎕㛽⚦⢩߮㛽⧘⚦⢩ᯏ⢻ォ౮࿃ሶߩM2HޔY2HޔIVVߦࠃࠆ PPI⸃ᨆࠍታᣉߒߚߩߎޕᖱႎࠍ1ߢᓧࠄࠇࠆ࠻ࡦࠬࠢࡊ࠻ࡓ-PPI࠺࠲ߦട߃ࠆߎߣ ߢ♖ࠅࠃޔᐲߩ㜞ォ౮࿃ሶࡀ࠶࠻ࡢࠢߩ᭴▽߇น⢻ߣߥߞߚޕ ਛᩭᯏ㑐ߣߩห⎇ⓥߢޔ⎕㛽⚦⢩ߩCAGE⸃ᨆࠍታᣉߒ⚿ߩߎޔᨐࠍ߽ߣߦ⎕㛽⚦⢩․ ⇣⊛ߥォ౮↥‛࠲ࡕࡠࡊޔ᭴ㅧޔncRNAߩหቯࠍⴕߞߡࠆޕ ᧲੩Ꮏᬺᄢቇ⊕㜯సᒾඳ჻ߣߩㅪ៤ߦࠃߞߡޔNFATc1ߩChIP on chip⸃ᨆߩḰࠍㅴ ߡࠆ⸃ߩߎޕᨆ⚿ᨐߦࠃࠅޔNFATc1ߩ⎕㛽⚦⢩․⇣⊛ߥᮡ⊛ㆮવሶߩหቯ߮⎕㛽⚦⢩ಽ ൻㆊ⒟ߦ߅ߌࠆNFATc1ߩേ⊛േߩ⸃ᨆ߇น⢻ߣߥࠆޕ ࡅ࠻ᧃ᪳ⴊ߆ࠄߩ⎕㛽⚦⢩ಽൻ⺃ዉ♽ߢ⸃ࡓ࠻ࡊࠢࠬࡦ࠻ޔᨆߩ⚿ᨐࠃࠅߒߚ ㆮવሶߩᯏ⢻⸃ᨆࠍⴕ߁ߚߦ᧲ޔ੩ᄢቇ⑺ጊᔀඳ჻ߣߩㅪ៤ߢဳࠬ࡞ࠗ࠙ࡠ࠻ޔ siRNAࠍ↪ߚࡁ࠶ࠢ࠳࠙ࡦ⸃ᨆࠍ੍ቯߒߡࠆޕ ߆ߕߐ࠺ࠖࠛࠛ⎇ⓥᚲฎ㑄Ყᔒඳ჻ߣߩㅪ៤ߦࠃߞߡ࠻ࡊࠢࠬࡦ࠻ޔ ࡓ⸃ᨆߩ⚿ᨐࠃࠅߒߚㆮવሶߩChIP on chip⸃ᨆ߮⾰㊂⸃ᨆࠍ↪ߚ࠲ࡦࡄࠢ ⶄว⸃ᨆࠍⴕ߁ߚߩ᛫ࠍታᣉਛߢࠆޕ ޣᒰ⎇ⓥߦ㑐ߒߡᵴ↪ߒߚ⎇ⓥ࠺࠲࠰ࠬޤ ⎕㛽⚦⢩㛽⧘⚦⢩ಽൻᤨߦ߅ߌࠆ♽ᤨ⊛ㆮવሶ⊒ᖱႎ ࡊ࠶࠻ࡈࠜࡓࠃࠅឭଏߐࠇࠆ22+ᖱႎ ޣਥߥ⎇ⓥ⺰ᢥߣߘߩⷐޤ 1. 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