Q 。 QQ

557
Q̲ Ῥ Ό̳QQQQQ
Vol. 34, pp. 557ῒ560, 2006
῝῞ῚῘ
῏ῑῒ῎῔῕ῌ̮̮῔῍ΐῐ
῔ῐῒ̮
ΐῑ῕̮
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῎ QῬ̲Ὸῌ̱̱Q῱Ὺ῎̮Q̰QῩῠQQῪῨῚ̰ῖ̮̯̰̰ῒ̯
̮Ὶ῍ ῖ̯̰῜QQ ΅̲ῶ̯ῡ῎ ̱ῼ̲` ῠQQ῝Q̯̰̰ ERAD ΐῴQ̮῎ QQQ
̰QῩΐQQῖ̰QQ “Hyper-ERAD ̯” ̯̮̯Qῐ̰̰̰῍ ̱ῼ̲` ῡQQ ΅̲ῶ
ῠQῚ̯QῬ῵ῌ̱ῷῸ̯̯̰̳ῙQῨQQ̮̰῎ QQῠQQΐQQ̮̰̰῍
Ίῗ῟Ῑ
̱ῼ̲` ῎ ̲ῲῶ ῱ῌῴ῎ QῩQQ̱ῥQ῎ Ῥ̲Ὸῌ̱̱῎ QQ ΅̲ῶ
Q̰QῩῪQ῏ῖ̰̳Qῠ῔῏ῪQῦῚ῍
ῑ῎ῒ῏
Iῌ ̮̮̮ΐ̮ῖῐ῔̮῍̮ῖ῕
QQῡ῎ Qῌ̮QῌQ̰ῠQ̯῕̯Ῠ 3 Q̱ῠ̳
̯̰QQῒ̰QQ̮̰̰῍ ῖ̯̰῜QQQῡ῎ ̮ῠ
ῥῗῡ̮ῧ̯ RA QQ΅̱ῚῲQ̰QῩῪ῱῎
3 QῠQQΐ̰̮̯῎̰Q̯῍̰Ὶῧ῎ Ὶ̯ῐῢQ
̯QQ̰QῩ̲ ῳ ῌΌ QQῪQQ̮῎ ̲ῸQ
Q̮̯QῩῠῦ̯ΰ̰̰̯῎̰QQQ̯ῡῥ῝Ὶ῕
̰QῩ cDNA ῭̲ ῌ̰̰῭῿ῼ̱ῳ ῌῺ
̳̯̰῎ QῠQ̯῕̰ΰ̰̰̮Q̯ῢQ̯QQ̯῍
̱ῪQ῝Ὶ῍ ῘῠQQ῎ ῾Ὼ ῌ̲Ύ῭̲ Ώ
̰̮̯ΐQῐ̰̰̰῍ ̮Ὶΐ῝̯῎ Ῐ̰Ῑ̰ῠQῩ
ῳῶ ̯῎῝ῚQQῠῥQῠῤῒ̯Q῕̰Qῠῳ
ΐQQῠQῩῩ῎ Ῐ̰̰ΐῥ̯ῖ̰ῥQ̯̯̯῜̮
ῌ Ὺ῕̰̮̯̯QQ̮῎ ̮ῠQQῥQῪQ̰Q
̰̯ΐ̰ῨῘῠQQQῪῨ῜Q̮̰Ὶῧ῎ 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῵
Q̯Q̰̮̰̯῔Ὶ῍ ̮ῒ̮̯ΐ̰῎ Q̰QῩ̯Q
̱̯῝Qῖ̰ῥQ̯῍̰̮̯ΐ̰̰ῒ̯̯῝Ὶ῍ ̮
̮̯ῡ῎ ῎ῥΊ̲ῌ῰ῌ̯̯̰̳ῒQῖ̰̰̰ῒ̯
ῒ̮̯ΐ̰῎ ̱ῼ̲` ῡ RA Q̰QQ̯ῑ῎
̯῝̯ῑ̰ῗ῎ QῩQῐ̮Qῡ Q̯̰̯ῥῥ̯῍
̯ῡQQ̯῝Qΐ̮ῧ̰̰ῚῚῧ῎ ̱ῼ̲` ῡ
̰῍ Ῐ̮̯̰̰̰̰ῡQ̰QῩ̯ῡ̳ῒῪQ̰Ὺῐ
Q̰QῩῠ̲ῌ῰ῌ̳ῒQ̯ῡ̯῕̯Ῠ RA ῠ῝
̯῎ Q̰QῩΐQQQ̮ῚQQ̯῍̰QQ ΅̲ῶ
Q̯Q῰ῖ̰ῥQ̯῍̰̮̯ΐQ῕QQ̮̰Ὶ῍
ῌRheumatoid arthritis: RA῍ QQQ̰QῩῪ῱῎̯῎
RA ̯ῡ῎ ̮ῥ̮ῥ̯ῡ ῠQQ̯῍ῦῩῧQῪ
῞῏QQ̯῎ ῘῠQQῠῦ̯̰ῗ̯ῖῩῌQQ῎ Q
Q̲ Ῥ Ό̳QQQ
̱ῼ῿̳QQQQῡΎ
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῏
Qῌ̲Q῰ῌ̳̱ ῺῳῌῪ ̲QQQ̯῟̯ΊQ
QQQῑQ῝῍ QῪ῝̯Q῝̯ῧῩ ῳ̳̲̰ῌ̱
ῴῴ´̳ῴ῞ῲ῞̮̰̰̮῎̯QQQQ̲ῴ´̳ῴ
ΐQῨQ̮̰῍ ῗ̰̯ῧῩQ̰̮̰Ῐ TNF-a ῦ
̯ῧΊ῜ῘQQ ΐ῟῜̮̰ΐ῍ ̮̰ΐ ERAD ῦ
IL-1b ̯῟῞῎ΊῘ̱Ῥ´῰Ῥ̳ΐQQQQ̯ῳ
UPR ̯ῙQ̳Q̰̲ῐΊQῴ ̯ῼ̰̮̰῞῍ Ί
̰῍ Q῝QQ̯ῑῧ̯QQ̯̰̰ῥῘῨ̮῍ ̲̳̲
Qῴ̯Q̳Q`̰Q̮̮῍ QQ̯Q̯Q̰ῌ ̮̯̰
ῴ῞Q̯̰̰QQ̰QῩ̮̰̮῞῝Q̮̲̯Qῌ̳
ῚΊQῴ̯ῴ´̳ῴ῵̳̱ῌ῞̮῜Q̳̮῜ῑῩ῍
Q̳Q̰Q῔Q̮̮῞QῐῨ̰῜῎̰5῍ῌ ̮ῒ̮̯
ERAD ῦ UPR ̯QQ̰̰ῒ̮Ῐῤ̯QQQQQ
ΐῨ῍ QQQῧQῦQ̱Ῥ´῰Ῥ̳QQ̯ῧΊ῜ῥ
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῞῝QQῳ̰̰Q῔Q̮̮̯ῒ῍ QQ
IIIῌ ῐῒΐ῏῕̮̮ῗ̮̮ῖῙ̮῔῎ῑ
ῳ̰ΐQ̮̰̮῞῝Q῝ΐ̮Q̮̰̰̯ῒ῍ ῗ̯῎
̮̰ῒ̯QQ̯̯QῨ̯῎ῌ
῝̯ΐQ̯̱̲̲` ̳ΐ RA Q῝̯QQ̮̰
̮̯῾̰Qῐ̰῞῍ ̰̰̰̰ΐῳ̳ῌ̲̳̱̮Ῐ
ῒQῒ̰Q ̮̰̮῞̰Q̲῞̮῍ ̱̲̲` ̳Q
̱̲̲` ̳̯ RA QQ῱̯̯Q̯̯QQ̮῜῎
῿QQ̯QQ ῭ῴ̰Q̰̮̰̮῞̰QῢῘῌ QQ
Ῐ̮῞ῒῨ῍ ̱̲̲` ̳ΐQQQ̲QῚ῝̯̯῕
̯Ῠ̯QQQQ Q̲̯Q̯QQ̮̰῾̳ ῌῸῌ
QQῳ̰̯̲̰̲̯QQ̮῜῎̰Q̳ῨΐQῐῨ̰
̰Q῎῜Q̰̰Q῏̮῞ΐQῡ̰Ῐΐ῍ QQQQ̯
Ῐῌ ῗ̮῝῍ ̱̲̲` ̳̯Q̮῜QQ̰ΰῤ̰̮
῎ῘΊ῜̯ῗ̯ 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῍ ̱̲̲` ̳Q῿QQ
̯̯῎ῒ῞Qῶ̮῍ ̳Q̯QQ̰ΰῤῘῌ
̯QQ ῭ῴ̰Q̰̮Ῐῌ ῗ̯QQ̱̲̲` ̳Q
῿QQ̯QQ ῭ῴ̯῍ ̱̯̱Q῝̯QῨQ̯̰῎
IIῌ ῐῒΐ῏῕̮῍̮Ῐ
̮̯῎̯ῥῒῒ̰Ῠ̮῍ ῗ̯ 3 QΐQQῳ̯̰Q῏
῝̯῍ RA QQ῱̯̯Q̯QQ̮῜῎̰̱̲̲`
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
Q῕ῠ̲̮ῘQQ῝ ῔Q̮̮̰῍ QQῚ̯̮̰Ῡ
̮῜῎̰̯ῦQ̰Ῡ̮ RA ῞῎῏QῘ̮Ῐ̰̮̰
ΐQΰQ̰̮̰̮῞῝̰̮ΐ῍῾̮̰̮῞ΐQQ̮
 ῔Q̮̮̮῞̰Ῡ̳̮῜ῑ̰῍ QῲQ῰̯ Ὶῧ
̰Ῐῌ ̱̳Ῡ̳῞Qῲ῍Q῞̯ῠ̲̮ῘQQ̯῏Ῑ
Q̰ῶ̯̮̰Ὸ̲ῼῌ̱ῌΐ̯Ῐ̮̰῜῎̯῎῞῎
CIA ῼῴ̲̰Ί̳̮Ῐ synoῐῒῑ ῝̯QῲQ῰̯῍Q
῏´῵ῒῩ b-Ὺ῰̱̲Ὸ̲ῼῌ̱ῌ̰Q̮̮ῘQ
ΐῺῐῩ̰῜῎Ῐ̮῞ῒῩ῍ QQQ̯ῑ῎῜QῧQ
Q῍ ̮̯Ῠ῏̯QῳQ῎̮Q̰̯̰̯QῚῘῌ
̮῜῎̰̱ῶῷ῭̲̲̯QῲQ῰̯῍Q̯QῩῒ̯
Q῝Qῷ̮῜῎̰̮῞ΐQQ̮̰Ῐῌ ̮̯̮῞̯῍
IVῌ ̮̮̮῕̮ῖῗ῜ῚῘΊ̮῔̮
̱ῶῷ῭̲̲ RNAi ΐῳΎ῵΅Ύ̲ῑQQ̯ῑ῎
Q̯ ‘gain-of-function’ ̯QQ̯QQῒῩ῍ ̱
῜ῦQῲQ῰̯῍Q̰ῺQ̮̰῞῎῏ in vitro ̯Q
ῶῷ῭̲̲̯ RA ῧQ̯Q῕Qῷ̮̰̮῞ΐQQ
Q̯ῨῚ῜ῦ̲Ὺ̮Ῡ̰῜῎̰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῰῍QῐQῥῦQ῰῔̱῵̲̱̯Ῠ
̯ῡQ῏Q̯QQ̯Ῠ̰̰Q̰
̰Q῰Qῥ̯ῦ̮̯Q̰῍ ̮̯̰ῙῪΌ῵ῌ̱̱̯
ῗ̮῍ QQῖQ῞̯Ὶ῜῎̰̮῞ΐ̱Ῡῒ῞̯Ὶ
ῺQ̯Ῠ̰ῦ̯῝῍̰̮῞ΐQQ̮̰ῘῘῌ ῗ̮
Ῐῌ ̮Ῡ̯῍ ̮̯ῡQ῏Q̯QQ̯QQQ̯῭Q ῝῍ CIA ῼῴ̲̰Ί̳̮ῘQῲQQ῝̯ῪΌ῵ῌ
Q̯Ῠ̰ῦ̯῝̯̯῕῍ ῏Q̰Q῏Q῝῍̰Q῎῝
̱̱̰Q̯̮Ῐ῞̮̰῍ synoῐῒῑ QῲQQ῝̯̱Q
̯Q῰῔̱῵̲̱ῶ̯Q̯ῪΌ῵ῌ̱̱̯῾Q̯Ῠ
QῺῬ̱QῲQQ̯῕Ῡῡῴ ̯ῪΌ῵ῌ̱̱ΐ῾
̰ῦ̯῝῍̰̮῞ΐQ̱̮̰Ῐ8῏ῌ ̱ῶῷ῭̲̲῞
Q ̮ ῜ ῎ ̰ ̮ ῞ ΐ Q ̱ ̮ ̰ Ῐῌ ̮ ̯ Q Q ῒ Ῡ῍
῎῏ 1 Ί̯ ῝Q̰Qῒ̮ῖ̯ΰ῝̮QῖQ῞̯̰
synoῐῒῑ QῲQ῰῝̯̱ῶῷ῭̲̲̯̲ΐῨQ̮̰
̮῞̯῍ ῧQQῚ̯ῦ̱ῶῷ῭̲̲̯QῥΐQΌ῝
̮῞῝ ERAD ̯QῥΐQQ̮῍ Q῰῔̯Qῥῦ
῍̰̮῞̰Q̮QQ῝῍ῚῘῌ
̮ῌῪΌ῵ῌ̱̱̰ῦῘῩ̮῍ 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῍ Q῰῔̯Q
̮ ῞ ̰ Q ΰ῍ ̱ ῶ ῷ ῭ ̲ ̲ ῝ Q ῠ ̱ ̲ ῺῬ̱
ῥῦ̮ῌῪΌ῵ῌ̱̱̰Q̰̮ῖ῍ QQ῞̮῜Qῲ
ῌsynoῐῒῑ῍ ̯QQ̳ῧQ̯Ῥῼῴ̲῝̰Ὸ̮̰῜῎
Q῰̯Q῍Q̰ ῔Q̮̮῜῎̰̯῝῍̰ῌ ῎῎ῒ
Ῡ῍ ̱ῶῷ῭̲̲ ῝Qῠ̱̲ῺῬ̱ ῌsyno
ῐῒῑ
̰ῲ̲ῌ῱̲ῶ̯QQQ̳ ῌcollagen induced ar-
ῐ̰̯QQ̯῍Q̮Ῐ RA QῲQ῰῞̯῍ ῱ΏQ
thritis: CIA῍ ῼῴ̲̰ΊῸ̮Ῐῌ ῗ̯QQ῍ CIA ῼ
῰῔̱῵̲̱̯ῨῚ῜Q̯ῡ῔̳̱̯῍̰ῦ̯ΐ῍
῝̯̱̳Ῡ̳̯QQ̯̳῟
̱ῶῷ῭̲̲̯ῑQ̯Ῠ̰ Hyper-ERAD ῞῎῏Q
̮῜῎̰̯ῦῒῒ̰Ῡ̮῍ QQ̳̯ῧQ̯ῙQQ̰
̮̯Ῐῥ̯ῪΌ῵ῌ̱̱̯῕̮ῙQQ̰Q̮῍ Q῔
ῴ̲̰Ί̳̮Ῐ syno
ῐῒῑ
Q̮̮῞ΐ̱Ῡῒ῞̯ῚῘῌ ̮Ῡ̯̮̯ῺῬ̱̯Q
QῚῘQ῰῝῍̰῍ RA ῞̯ Hyper-ERAD ̯Ῠ̰
Q̯QQQῚ̯Q̯̰QῚῘ῞̮̰῍ ̳QQQ῰̯
QῲQ῰ΐQ῍Q̮ῘQQ῝῍̰῞QῐῩ̰̰ῌ ̮
Qΰ̯ῤῥῩ̰Ῐῦ̯̯῍ QῲQ῰̯῍QΐQ̮Ὶ
̯῜̯Q̮῜̯῍ QQQ̯̰ῌ῝Q῰῔̱῵̲̱ΐ
῜῎̯῎̮῞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῾̯῍ ῳῶ῰ῶ῱
̮QQ῕Ί̮῎ῡ̮Ὶ̳QQ̳Q̯Q῎̯
Q῕῿Q῎Ὶ̮ῡῖῌ
ῶQQQ῍ Machado-Joseph Q̯QQ̮̰Ῡ̱̱Ύ
ῑ
ῴ`̱ῶQῥ῍ QQQQ῍QQQQ̱ῌ̰ῶ΅ῶQ
̯̯̯QQQQQ῾ΐῦ῕Qῧ̰῞῎Ῡΐ῍ ̮̰ῧ
̯῎ῗ̰ῤ ERAD ̯QQ̯ῦῩῤ̯῟
9῍10῍
ῐ
1῎ Amano T, Yamasaki S, Yagishita N῍ et al.
῍ Q̲
Genes Dev. 2003; 17: 2436῏2449.
´῎ΐQ̮Ὶ ERAD ̯῏QΐΌ῔ ̮ῖῦ῏̯Q
2῎ Yamasaki S, Yagishita N, Tsuchimochi K, et
῾ ̯ ῌ ̰ ῢ ̯ ῎ῌ Q ῝ ῞ ´῎ ΐ Q Q ̮ Ὶ QΏ̯
al. Arthritis Research & Therapy 2005; 7:
ERAD ̯Q῾῍ ῑῦῠῙ̯QQ̰Qῐ῞῎῕Q῟
181῏186.
QῚ̯̲Q̰Qῖῤ̯̯̯Ῠ῍ RA Q̳̯ῢ̯ῧῗ
3῎ Yagishita N, Yamasaki S, Nishioka K, et al.
`ῶ̱ῪQQ̲̳̯Q̳̯ῤQῚ̯Q̲ῒῨ̰Q̮
Future Rheumatology 2006; 1: 3῏36.
Ὶῤ̯̯Q̮῞ ̰̯῎ῌ
4῎ Feldmann M, Brennan F. M and, Maini R. N.
Cell 1996; 85: 307῏310.
ῌ῏῎῍
5῎ Rehman Q and Lane N. E. Arthritis Res 2001;
Q̲̯Ὸ῎̯Q̳ῒῧ῍ ̲QQQ̯QQQ῭῱῵
3: 221῏227.
῭̯ῦῩQQ`ῶ̱ῪQ̰QQ̮QQ̯ῸQ̯῎῏
6῎ Clair E. W. S. Ann. Rheum. Dis. 2002; 61:
QQ̰Q῝῞῎Ῡ̯῟῍Ῠ῍ Ῑ̯ Q̯QQῖ̯̰
67῏69.
῜ ERAD ̯῎῏QQ̰QῒῖῚΰ̯ Q Q
7῎ Science “Editor’s choice” 2003; 302: 199.
̰ῼQ̯QῺ̮Ῐ῞̮῞̮ῡ῏̮̯ΐ῍ ̲QQQ̯
8῎ Yagishita N, Ohneda K, Amano T, et al. J
̰̱῱ῌῬ῭̯̲Q῍ RA ̯̲QQQῼQQ̯῎῏
Biol. Chem. 2005; 280: 7909῏7916.
QQ̰ῤῚῧῖ̮̯ΐQῧῒ̯̯῝Ὶῌ QQ̯῎
9῎ Imai Y, Soda M, Inoue H, et al. Cell 2001; 105:
῏QQ̯ ̳̯̯ῒ῟῍ ̲QQQΐQQ̯QQ̯Q
891῏902.
ῐῧ̰ΐ῜̯QQQ̰Q῎῞QQ̯ Q̰̳QῖῩ
10῎ Bence N. F, Sampat R. M. and Kopito R. R.
Ὶΰ̯ῸQ̯῎῏QQ̰Q῜Q̮Ῡ̮̯̯῍ Q̯Q
Science 2001; 292: 1552῏1555.
̯Q̮̰̯ΐῧ QQ῟Qῧ̯QQ̰ΏῚῖῚΰ̯
11῎ Tuchimochi K, Yagishita N, Yamasaki S, et
̲Q̮ῚQQ̯ Q̯̯ῒῤ̮̰̯῎ῌ ̮ῧ̯Q
al. Mol. Cell Biol 2005; 25: 7344῏7356.
12῎ Yamasaki S. EMBO J 2007; 26: 113῏122 ῌ2007῍.
̳῍ Ῥῲ̱̰̱ῶ̯ Qΐ p53 ῟῍Ῡ̮̯̰QQ
̮Ὶ12῍ῌ
30