557 Q̲ Ῥ Ό̳QQQQQ Vol. 34, pp. 557ῒ560, 2006 ῝῞ῚῘ ῏ῑῒ῎ῌ̮̮῍ΐῐ ῐῒ̮ ΐῑ̮ Qΐ ̱Ί ῎Qῠ : ῦQ 19 ῗ 2 Q 1 ̮῏ ̯ Q῏ῡQQ ΅̲ῶQ̰QῩ̰̰ E3 ̲ῲῶ ῌῴQQῪQ῞QQ ´ῳQῠ ῐ̱ ῼ̲` ῑ Ὺῳ ῌῺ ̱̮ῌ ̱ῼ̲` ̳ῒQQῧ̲΅̱ῠQQ̰̰῎ ̱ῼ̲` ῡ ERAD ̯ῑ῎̯QῙ̮῎ QῬ̲Ὸῌ̱̱QῪ῎̮Q̰QῩῠQQῪῨῚ̰ῖ̮̯̰̰ῒ̯ ̮Ὶ῍ ῖ̯̰QQ ΅̲ῶ̯ῡ῎ ̱ῼ̲` ῠQQ῝Q̯̰̰ ERAD ΐῴQ̮῎ QQQ ̰QῩΐQQῖ̰QQ “Hyper-ERAD ̯” ̯̮̯Qῐ̰̰̰῍ ̱ῼ̲` ῡQQ ΅̲ῶ ῠQῚ̯QῬῌ̱ῷῸ̯̯̰̳ῙQῨQQ̮̰῎ QQῠQQΐQQ̮̰̰῍ Ίῗ῟Ῑ ̱ῼ̲` ῎ ̲ῲῶ ῌῴ῎ QῩQQ̱ῥQ῎ Ῥ̲Ὸῌ̱̱῎ QQ ΅̲ῶ Q̰QῩῪQ῏ῖ̰̳Qῠ῏ῪQῦῚ῍ ῑ῎ῒ῏ Iῌ ̮̮̮ΐ̮ῖῐ̮῍̮ῖ QQῡ῎ Qῌ̮QῌQ̰ῠQ̯̯Ῠ 3 Q̱ῠ̳ ̯̰QQῒ̰QQ̮̰̰῍ ῖ̯̰QQQῡ῎ ̮ῠ ῥῗῡ̮ῧ̯ RA QQ΅̱ῚῲQ̰QῩῪ῎ 3 QῠQQΐ̰̮̯῎̰Q̯῍̰Ὶῧ῎ Ὶ̯ῐῢQ ̯QQ̰QῩ̲ ῳ ῌΌ QQῪQQ̮῎ ̲ῸQ Q̮̯QῩῠῦ̯ΰ̰̰̯῎̰QQQ̯ῡῥ῝Ὶ ̰QῩ cDNA ῭̲ ῌ̰̰῭ῼ̱ῳ ῌῺ ̳̯̰῎ QῠQ̯̰ΰ̰̰̮Q̯ῢQ̯QQ̯῍ ̱ῪQ῝Ὶ῍ ῘῠQQ῎ ῾Ὼ ῌ̲Ύ῭̲ Ώ ̰̮̯ΐQῐ̰̰̰῍ ̮Ὶΐ῝̯῎ Ῐ̰Ῑ̰ῠQῩ ῳῶ ̯῎῝ῚQQῠῥQῠῤῒ̯Q̰Qῠῳ ΐQQῠQῩῩ῎ Ῐ̰̰ΐῥ̯ῖ̰ῥQ̯̯̯̮ ῌ Ὺ̰̮̯̯QQ̮῎ ̮ῠQQῥQῪQ̰Q ̰̯ΐ̰ῨῘῠQQQῪῨQ̮̰Ὶῧ῎ Ῐ̰Ῑ̰ Ῡ ῌsynovial cell῍ ̯̯ῦ ‘̱ῼ̲` ῌSynovio- ̯̮ῌῐ̯QῙῪ῭̮̯῎̰̳ῙQΐQQ̮̰̰῍ lin῍’ ̯̰̰̮Ὶ1ῒ3῍῍ ̰̰̰̰ῡ̱ῼ̲` ΐQ̰ QQQῪQQῖ̰QῩῠ῏῎ QQῩῌ̮QQῩῠ QῩῪ῏Q῟̮̰ῥQ̯῍̰̮̯ῪQQ̮QQῪQ QῙ̯Q̮̯ῡ῎ QῗῠῥQQῤQῠ῝ῑ̯̰̰Q ῧῚΐ῎ `Q̯῟̮̱ῼ̲` ῡ῎Qῡ ̲ῲ Q̯Q̰̮̰̯Ὶ῍ ̮ῒ̮̯ΐ̰῎ Q̰QῩ̯Q ̱̯῝Qῖ̰ῥQ̯῍̰̮̯ΐ̰̰ῒ̯̯῝Ὶ῍ ̮ ̮̯ῡ῎ ῎ῥΊ̲ῌῌ̯̯̰̳ῒQῖ̰̰̰ῒ̯ ῒ̮̯ΐ̰῎ ̱ῼ̲` ῡ RA Q̰QQ̯ῑ῎ ̯῝̯ῑ̰ῗ῎ QῩQῐ̮Qῡ Q̯̰̯ῥῥ̯῍ ̯ῡQQ̯῝Qΐ̮ῧ̰̰ῚῚῧ῎ ̱ῼ̲` ῡ ̰῍ Ῐ̮̯̰̰̰̰ῡQ̰QῩ̯ῡ̳ῒῪQ̰Ὺῐ Q̰QῩῠ̲ῌῌ̳ῒQ̯ῡ̯̯Ῠ RA ῠ῝ ̯῎ Q̰QῩΐQQQ̮ῚQQ̯῍̰QQ ΅̲ῶ Q̯Qῖ̰ῥQ̯῍̰̮̯ΐQQQ̮̰Ὶ῍ ῌRheumatoid arthritis: RA῍ QQQ̰QῩῪ῎̯῎ RA ̯ῡ῎ ̮ῥ̮ῥ̯ῡ ῠQQ̯῍ῦῩῧQῪ ῞῏QQ̯῎ ῘῠQQῠῦ̯̰ῗ̯ῖῩῌQQ῎ Q Q̲ Ῥ Ό̳QQQ ̱ῼ̳QQQQῡΎ ῳ̯Q̯̯QQῠQQ̯ῨῘῥ̮̰̰̮̯ῒ̰῎ ̮̯Q̱QQ̱ ῌ Quality of life ῪQῖQ̯ῐ̯QQ̯῎ῐ̰῍ QQ῎ 27 ´ QQ 558 ̰ΐQ̯ RA Q̮̯ 70 Qῤ῞ῥ 100 Qῤ῞ῥ῎̰ Q̮̰Ῐῤ̯Q̰̰ΰῤῘQQ῍ ̱̲̲` ̳̯ ̰῍ ῡῘQQQ̯῞ῥ̯῎ῗ̯Q̮ῥ̯̳῎ῳQQ RING Όῌ̲̰Q̮̰ E3 ̲ῲΌ̳ ῌῶ῝ Q̯῍̰῞῎̰̰῎̰ῌ ῦQ̲̯Q̰῞ῤQ̯Q ῍Ῡ῍ ̯ῒ῝ῥΊQῴQQQQ ῌEndoplasmic re- 1ῐ ΐ̮̯ῑQ̯QQ̮῎̰῞ῥ̮̰ ῍ ῡῘ̮ ticulum associated degradation: ERAD῍ ̯ῑ῎ ̰̯ῧ̰QQ̲̱ῐ̯῍ ῬΰQ̯QQ῝ GDP ̯Q Q̳̮̰Q῝῍̰̮῞ΐQῨῒ῞̯ΊῘῌ 4῍ 1.2ῐ ̯ῥῺ̮̰῞QῘ̮̰῎̰ῌ ̮̯ῧ῏̯ ῡQ̰Q̯ΊQῴ῝̯῍ QQῒ῝QῩ̮̰ῘQῸ Q̲QQῒῨ῍ WHO ῝̯ 2000 ̳ῧῩ “The Bone ̳̲ῳῒῦQQῸ̳̲ῳῒ̯̲΅ῌ̳ῼΎ̳̱ΐQ and Joint Decade”῍ ̰ΐQ῝̯ 2001 ̳ῧῩ ῎Qῌ ̰̰ῑῩ῍ ̮̮῝̰Q̯QῴQ̱̰Q ̮ῘῸ̳ QῪῑQῧ̳ 10 ̳QQ῏ ῞῎ΊῘῲ ̳ῌ̳ΐ ̲ῳῒ̯̱̳̱ῴ̳Q̯QQQQ̯ΰΰ̮῞ΐ῝ QQ̮̰Ῐῌ ῦQ´῝̮̰ῠ῟ῡ῝̯̮̯ῑQΐQ ̰ΐ῍ QῌQ̱QῩ̯ῐ̳̮ῘQQQ̯Q̰ῥ̮ ῸQ̮̰῎̰̯̯῍ ῗ̯QQ̲̯῍QQΐQQ̮ ̯̳Q̮̰̰ῌ ̮̯QQQ̰ ̲ῲΌ̳ῌ῾̳ΏῪ ̰ῑῨ̮῍ ῍QQ῞῎ῐ̯̮̰ῡ῝̯῞̮̰῝ ῷῌ Q̯ῧῩQQ̮̰QQΐ ERAD ῝῍Ῡ῍ Q QQ̯̮Q̮῍ QQ̲̯QῸ̰QQ̮̰ῥ̯῝̯̯ QQ̯̮Q̰QQ̲̯Q῏Ῐῤ̯ΊQῴ̱ ̳̳ ῎Ῐῤ῝῍̰ῌ ῗ̮῍ ̯ῖQ῍̲῍QΐΐQ̮ ̯ ̲ ̰ Q ̮ ̰ UPR ῌUnfolded protein re- ῎̯῎̯ῒ῞῎ῐ̯῍ RA ̯῍ ῎ῡῙῗ̯Q῝̯Q sponse῍ ῞῞ῥ̯ΊQῴ῝Ὸ̳̲ῳῒ̯QῒQQ̰ Q̮Ῠ`QΐQQ̮̰῎̯῎Ῐῤ̯̯῝῍̰ῌ QΊ῎̰ῌ ̮Ῠ̯̮̰Ῠ̯QQῸ̳̲ῳῒ̯Q ̮̰ῡ῝̯QQ̯ῧ̰ΏQῒῨ῍ RA ̯QQ̯῏ Qῌ̲Qῌ̳̱ ῺῳῌῪ ̲QQQ̯῟̯ΊQ QQQῑQ῝῍ QῪ῝̯Q῝̯ῧῩ ῳ̳̲̰ῌ̱ ῴῴ´̳ῴ῞ῲ῞̮̰̰̮῎̯QQQQ̲ῴ´̳ῴ ΐQῨQ̮̰῍ ῗ̰̯ῧῩQ̰̮̰Ῐ TNF-a ῦ ̯ῧΊῘQQ ΐ῟̮̰ΐ῍ ̮̰ΐ ERAD ῦ IL-1b ̯῟῞῎ΊῘ̱Ῥ´Ῥ̳ΐQQQQ̯ῳ UPR ̯ῙQ̳Q̰̲ῐΊQῴ ̯ῼ̰̮̰῞῍ Ί ̰῍ Q῝QQ̯ῑῧ̯QQ̯̰̰ῥῘῨ̮῍ ̲̳̲ Qῴ̯Q̳Q`̰Q̮̮῍ QQ̯Q̯Q̰ῌ ̮̯̰ ῴ῞Q̯̰̰QQ̰QῩ̮̰̮῞῝Q̮̲̯Qῌ̳ ῚΊQῴ̯ῴ´̳ῴ̳̱ῌ῞̮Q̳̮ῑῩ῍ Q̳Q̰QQ̮̮῞QῐῨ̰῎̰5῍ῌ ̮ῒ̮̯ ERAD ῦ UPR ̯QQ̰̰ῒ̮Ῐῤ̯QQQQQ ΐῨ῍ QQQῧQῦQ̱Ῥ´Ῥ̳QQ̯ῧΊῥ Q῞̮ῗQ̯QQ̰QῘ̮῎̰ῌ RA ̯ΰQ̰Qῧ῝̯῎῝QΐQ 25ῐ ̱Q̮̰ ̱̲̲` ̳ΐ̮̯ῧ῏̯QQQQQQ῞̮Q ̮῞̰Qῐ̰῞ ῍ QQQ̲QῚ̯ῢ῝̯ῗ̯Q῝ ̳̰Q̮̰̮῞̯῍ RA ̯Q῝̰QῐῘ῏ῐ῝ῷQ QQ̯`̯ΎQ῝̯῎ῌ ̮̯̰Ὶ῍ Q΅῞̮ QQῠ῎QQ῝῍Ῡ῍ RA ̯̯Ῐ̯Q῝QῚQQ̯ ̯ῖQQQQΐῳ̯̮̰̯ῒ῞῎῏QῸΐQῩ῍ Q Q̳ῨΐQῶ̮̰Ῐῌ 6῍7῍ ῝ΐQ̮̰̮῞῝QQῳ̰̰QQ̮̮̯ῒ῍ QQ IIIῌ ῐῒΐ῏̮̮ῗ̮̮ῖῙ̮῎ῑ ῳ̰ΐQ̮̰̮῞῝Q῝ΐ̮Q̮̰̰̯ῒ῍ ῗ̯῎ ̮̰ῒ̯QQ̯̯QῨ̯῎ῌ ῝̯ΐQ̯̱̲̲` ̳ΐ RA Q῝̯QQ̮̰ ̮̯῾̰Qῐ̰῞῍ ̰̰̰̰ΐῳ̳ῌ̲̳̱̮Ῐ ῒQῒ̰Q ̮̰̮῞̰Q̲῞̮῍ ̱̲̲` ̳Q ̱̲̲` ̳̯ RA QQ̯̯Q̯̯QQ̮῎ QQ̯QQ ῭ῴ̰Q̰̮̰̮῞̰QῢῘῌ QQ Ῐ̮῞ῒῨ῍ ̱̲̲` ̳ΐQQQ̲QῚ῝̯̯ ̯Ῠ̯QQQQ Q̲̯Q̯QQ̮̰῾̳ ῌῸῌ QQῳ̰̯̲̰̲̯QQ̮῎̰Q̳ῨΐQῐῨ̰ ̰Q῎Q̰̰Q῏̮῞ΐQῡ̰Ῐΐ῍ QQQQ̯ Ῐῌ ῗ̮῝῍ ̱̲̲` ̳̯Q̮QQ̰ΰῤ̰̮ ῎ῘΊ̯ῗ̯ Q̲̯QQ̰Q ̮̰῾̳ ῌ ῞῝῍ ῖQ̯῏QQQῑQ῞῎῏Q῾ῒῨ̯Q῝῞ Ὸῌ̮Ῠ ̲̮̰῎̯῎ῌ ῗ̮῝῍ QQQQ῝̯ ̯Q̰Ῡ̯̮´̮Ῐ̮̰ῡ῝̯QQ῞̯Q̯̰Q῾ QQQ ̰Qΰ῾̳ ῌῸῌ῞῎῏QQ῝῍ b-Ὺῳ ῒῨ RA ̯Q῝QῚ̰QQ̮̰̮῞ΐ῝̰̯῝ Ό̳῾̳ ῌῸῌ̰῭Ό̮῍ ̱̲̲` ̳QQQ ̯̯῎ῒ῞Qῶ̮῍ ̳Q̯QQ̰ΰῤῘῌ ̯QQ ῭ῴ̰Q̰̮Ῐῌ ῗ̯QQ̱̲̲` ̳Q QQ̯QQ ῭ῴ̯῍ ̱̯̱Q῝̯QῨQ̯̰῎ IIῌ ῐῒΐ῏̮῍̮Ῐ ̮̯῎̯ῥῒῒ̰Ῠ̮῍ ῗ̯ 3 QΐQQῳ̯̰Q῏ ῝̯῍ RA QQ̯̯Q̯QQ̮῎̰̱̲̲` QῪ῝̰Q῝̮̰̮῞ΐQῨῒ῞̯ΊῘῌ `ῢῨ̯ ̳̯Q̳῞̯QῴQ῝῍̰῏ῒῌ ῡ̮̮̯῾̰Q ̱̲̲` ̳̰Q̯QQ̮̮ῘQQ῍ QῪ῝῞῎῏ 28 ̱ῶῷ῭̲̲῞QQ̲ῬῺ̱ 559 ̱ ̯̰QQ̰Q̮Ῐ̮῞̯̮΅QῳQ῎ῦ̯῝ Ῠ̰ῧQ̮̰̯῝̯̯῍ ̱̳Ῡ̳῞Qῲ῍Q῞ΐ ῍ῚῘῌ ̮̰̯῍ ̱ῶῷ῭̲̲ΐ´ῷ`̱̱̯ῧQ Qῠ̲̮ῘQQ῝ Q̮̮̰῍ QQῚ̯̮̰Ῡ ̮῎̰̯ῦQ̰Ῡ̮ RA ῞῎῏QῘ̮Ῐ̰̮̰ ΐQΰQ̰̮̰̮῞῝̰̮ΐ῍῾̮̰̮῞ΐQQ̮ Q̮̮̮῞̰Ῡ̳̮ῑ̰῍ QῲQ̯ Ὶῧ ̰Ῐῌ ̱̳Ῡ̳῞Qῲ῍Q῞̯ῠ̲̮ῘQQ̯῏Ῑ Q̰ῶ̯̮̰Ὸ̲ῼῌ̱ῌΐ̯Ῐ̮̰῎̯῎῞῎ CIA ῼῴ̲̰Ί̳̮Ῐ synoῐῒῑ ῝̯QῲQ̯῍Q ῏´ῒῩ b-Ὺ̱̲Ὸ̲ῼῌ̱ῌ̰Q̮̮ῘQ ΐῺῐῩ̰῎Ῐ̮῞ῒῩ῍ QQQ̯ῑ῎QῧQ Q῍ ̮̯Ῠ῏̯QῳQ῎̮Q̰̯̰̯QῚῘῌ ̮῎̰̱ῶῷ῭̲̲̯QῲQ̯῍Q̯QῩῒ̯ Q῝Qῷ̮῎̰̮῞ΐQQ̮̰Ῐῌ ̮̯̮῞̯῍ IVῌ ̮̮̮̮ῖῗῚῘΊ̮̮ ̱ῶῷ῭̲̲ RNAi ΐῳΎ΅Ύ̲ῑQQ̯ῑ῎ Q̯ ‘gain-of-function’ ̯QQ̯QQῒῩ῍ ̱ ῦQῲQ̯῍Q̰ῺQ̮̰῞῎῏ in vitro ̯Q ῶῷ῭̲̲̯ RA ῧQ̯QQῷ̮̰̮῞ΐQQ Q̯ῨῚῦ̲Ὺ̮Ῡ̰῎̰ῌ ̮̯Ῠ῏̯ ‘loss- ̮̰ῘῘῥ῍ Q̯ ‘loss-of-function’ ̯Q̲῝QQ of-function’ ̯QQ̯QQῒῩῦ῍ ̱ῶῷ῭̲̲̯ ̰ Q ῥ ̰ Ῐῥ῍ ̱ ῶ ῷ ῭ ̲ ̲ ῝ Q Qῒ ῺῬ̱ Qῲ῍Q̯Q ̮̰QQQ̯ῧQ̯̰Q̯ Q῝῍ ῌsyno ̰̮῞ΐQ̱̮̰Ῐῌ ῑῒῑ ῍ ̰QQ̮QQ̰QῚῘQQ῍ Q̯ syno ῑῒῑ ΐ̮Q 13.5 ῢ̲ῢ῝̯ῖQ῞̯̰̮῞̰̱Ῡῒ῞ Vῌ Hyper-ERAD ῝ῐ῎῏Ῑ῍ῑΐῒ RA ̮Ῐῌ QQ̯ῺῬ̱̯ῧQ̯ῑ῎̮̯QQ̯῍ ῏ Q̰̳ῤQΐῼQῌ῎ Q῏Q῏ῒῩ̮QQ῎῎ῡQ ῝̯῟̯Ῠ῏̯̮̱ῶῷ῭̲̲ΐQῲ῍Q̯Q ῏Q῏ῠ῞ Q̮̰QQ῝῍̰῍ ̮̰ῢ῝̯`Qῒ ῷ̮̰̯ῒῌ QQ̯῞ῑ̰῍ ̱ῶῷ῭̲̲̯Q Ῡ̮̯QQ̯ῖQ῞̯̰ῺῬ̱̯῏QQ̯QQ̯Ῠ ̱̲̱̯̮̰QQQ´QQ῞̮ ERAD ̯ῑ ̰̰QῌῖQ῞̯̰ῦ̯ΐ῞Ὶ̯ΐ῎̮῞ΐ̮Ῡ ῎Qῥ̮῎̰̮῞ῒῩ῍ QQ̯ῧQ̮Ῐ̱ῶῷ ̰῎̰ῌ ῗ̮῝῍ synoῑῒῑ ̯῏Q̯Q̮̰Qῤ̮ ῭̲̲̯QῲQ῍QῐQῥῦQ̱̲̱̯Ῠ ̯ῡQ῏Q̯QQ̯Ῠ̰̰Q̰ ̰QQῥ̯ῦ̮̯Q̰῍ ̮̯̰ῙῪΌῌ̱̱̯ ῗ̮῍ QQῖQ῞̯Ὶ῎̰̮῞ΐ̱Ῡῒ῞̯Ὶ ῺQ̯Ῠ̰ῦ̯῝῍̰̮῞ΐQQ̮̰ῘῘῌ ῗ̮ Ῐῌ ̮Ῡ̯῍ ̮̯ῡQ῏Q̯QQ̯QQQ̯῭Q ῝῍ CIA ῼῴ̲̰Ί̳̮ῘQῲQQ῝̯ῪΌῌ Q̯Ῠ̰ῦ̯῝̯̯῍ ῏Q̰Q῏Q῝῍̰Q῎῝ ̱̱̰Q̯̮Ῐ῞̮̰῍ synoῐῒῑ QῲQQ῝̯̱Q ̯Q̱̲̱ῶ̯Q̯ῪΌῌ̱̱̯῾Q̯Ῠ QῺῬ̱QῲQQ̯Ῡῡῴ ̯ῪΌῌ̱̱ΐ῾ ̰ῦ̯῝῍̰̮῞ΐQ̱̮̰Ῐ8῏ῌ ̱ῶῷ῭̲̲῞ Q ̮ ῎ ̰ ̮ ῞ ΐ Q ̱ ̮ ̰ Ῐῌ ̮ ̯ Q Q ῒ Ῡ῍ ῎῏ 1 Ί̯ ῝Q̰Qῒ̮ῖ̯ΰ῝̮QῖQ῞̯̰ synoῐῒῑ QῲQ῝̯̱ῶῷ῭̲̲̯̲ΐῨQ̮̰ ̮῞̯῍ ῧQQῚ̯ῦ̱ῶῷ῭̲̲̯QῥΐQΌ῝ ̮῞῝ ERAD ̯QῥΐQQ̮῍ Q̯Qῥῦ ῍̰̮῞̰Q̮QQ῝῍ῚῘῌ ̮ῌῪΌῌ̱̱̰ῦῘῩ̮῍ QQ῞̮QῲQ Ῐ῞̮̰῍ syno ῑῒῑ Q̯Ῠ῏̯ synoῑῒῑ ̯̮QῖQ῞̯̰̮῞ῒ ̯῍Q̰ῺQ̮῎̰̮῞ΐ̱Ῡῒ῞̯ῚῘῌ Q̯ ῍ ̰ ῎ῐ̯῍ ̱ῶῷ῭̲̲ΐQQ̯ῧQ̮῎̰ RA Ὸ῎ RA ῧQ῞̱ῶῷ῭̲̲̯ Q̰Q̱̮̰ QῲQ῝̯ ERAD ̯Qῥΐ῾Q̮῍ Q̯Q ̮ ῞ ̰ Q ΰ῍ ̱ ῶ ῷ ῭ ̲ ̲ ῝ Q ῠ ̱ ̲ ῺῬ̱ ῥῦ̮ῌῪΌῌ̱̱̰Q̰̮ῖ῍ QQ῞̮Qῲ ῌsynoῐῒῑ῍ ̯QQ̳ῧQ̯Ῥῼῴ̲῝̰Ὸ̮̰῎ Q̯Q῍Q̰ Q̮̮῎̰̯῝῍̰ῌ ῎῎ῒ Ῡ῍ ̱ῶῷ῭̲̲ ῝Qῠ̱̲ῺῬ̱ ῌsyno ῐῒῑ ̰ῲ̲ῌ̲ῶ̯QQQ̳ ῌcollagen induced ar- ῐ̰̯QQ̯῍Q̮Ῐ RA QῲQ῞̯῍ ΏQ thritis: CIA῍ ῼῴ̲̰ΊῸ̮Ῐῌ ῗ̯QQ῍ CIA ῼ ̱̲̱̯ῨῚQ̯ῡ̳̱̯῍̰ῦ̯ΐ῍ ῝̯̱̳Ῡ̳̯QQ̯̳῟ ̱ῶῷ῭̲̲̯ῑQ̯Ῠ̰ Hyper-ERAD ῞῎῏Q ̮῎̰̯ῦῒῒ̰Ῡ̮῍ QQ̳̯ῧQ̯ῙQQ̰ ̮̯Ῐῥ̯ῪΌῌ̱̱̯̮ῙQQ̰Q̮῍ Q ῴ̲̰Ί̳̮Ῐ syno ῐῒῑ Q̮̮῞ΐ̱Ῡῒ῞̯ῚῘῌ ̮Ῡ̯̮̯ῺῬ̱̯Q QῚῘQ῝῍̰῍ RA ῞̯ Hyper-ERAD ̯Ῠ̰ Q̯QQQῚ̯Q̯̰QῚῘ῞̮̰῍ ̳QQQ̯ QῲQΐQ῍Q̮ῘQQ῝῍̰῞QῐῩ̰̰ῌ ̮ Qΰ̯ῤῥῩ̰Ῐῦ̯̯῍ QῲQ̯῍QΐQ̮Ὶ ̯̯Q̮̯῍ QQQ̯̰ῌ῝Q̱̲̱ΐ ῎̯῎̮῞ΐ̱Ῡῒ῞̯ῚῘῌ ̮̯QQῒῩ῍ Q ΎQ̮̰῎̰̮῞῍ ῢῘ̱ῶῷ῭̲̲ ῝QQQ Q̳̯̮̰ῢ῝QῐῩ̰῎ῘῨ῏̯ ̲̯QQ̯ ῧQῺῬ̱ῧ RA QῲQQ῝̯ ERAD ̱̱̱Ώΐ 29 QQQQ 560 ῏Q̮῞῎Ῡ̮̯ῤQQ̯QQ̮῞῎Ῡῌ QQ ERAD ̯ῷQΐΌ ̮ῖQ῾̯῍ ῳῶῶ ̮QQΊ̮῎ῡ̮Ὶ̳QQ̳Q̯Q῎̯ QQ῎Ὶ̮ῡῖῌ ῶQQQ῍ Machado-Joseph Q̯QQ̮̰Ῡ̱̱Ύ ῑ ῴ`̱ῶQῥ῍ QQQQ῍QQQQ̱ῌ̰ῶ΅ῶQ ̯̯̯QQQQQ῾ΐῦQῧ̰῞῎Ῡΐ῍ ̮̰ῧ ̯῎ῗ̰ῤ ERAD ̯QQ̯ῦῩῤ̯῟ 9῍10῍ ῐ 1῎ Amano T, Yamasaki S, Yagishita N῍ et al. ῍ Q̲ 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