Æú¸® ±Û·çŸ¹Î ÅðÇ༺ ³úÁúȯ ´Ü¹éÁúÀÎ ATXN1°ú CapicuaÀÇ º¹ÇÕü ±¸Á¶¸¦ ÅëÇÑ
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Structural basis of protein complex formation and reconfiguration by polyglutamine disease protein Ataxin-1 and Capicua / Genes Dev. 2013 Mar 15;27(6):590-5
1. ¿¬±¸¹è°æ
Æú¸® ±Û·çŸ¹Î ÅðÇ༺ ³ú ÁúȯÀº, ±× Áúº´ ¿øÀÎ ´Ü¹éÁúÀÇ ±Û·çŸ¹Î ¾Æ¹Ì³ë»ê ¹Ýº¹¼¿ÀÇ È®ÀåÀ¸·Î ÀÎÇØ ¹ßº´ÀÌ µÇ´Â »ó¿°»öü ¿ì¼ºÀ¯Àü¼º ½Å°æ ÁúȯÀÌ´Ù. ÇöÀç±îÁö ÃÑ 9°¡ÁöÀÇ Æú¸® ±Û·çŸ¹Î Áúº´µéÀÌ ¾Ë·ÁÁ® ÀÖÀ¸¸ç, ´ëÇ¥ÀûÀ¸·Î´Â ôÃß¼Ò³ú¼º ¿îµ¿ ½ÇÁ¶Áõ, ÇåÆÃÅϾ¾ º´ µîÀÌ ÀÖ´Ù.
ôÃß¼Ò³ú¼º ¿îµ¿ ½ÇÁ¶Áõ ŸÀÔ1 (Spinocerebellar Ataxia Type 1) Áúº´Àº ATXN1 ´Ü¹éÁúÀÇ Æú¸® ±Û·çŸ¹Î ºÎºÐÀÇ È®Àå¿¡ ÀÇÇؼ ¹ßº´ÇÑ´Ù°í ¾Ë·ÁÁ® ÀÖÀ¸¸ç, º¸ÇàÀå¾Ö, ºÎÁ¤È®ÇÑ ¹ßÀ½, ºÒ±ÕÇü, ±Ù·ÂÀúÇÏ, ¿¬ÇÏÀå¾Ö µîÀÇ Áõ»óÀ» º¸ÀδÙ. ATXN1 ´Ü¹éÁúÀº ¸ö Àüü¿¡¼ ¹ßÇöµÇ´Â ´Ü¹éÁúÀÌÁö¸¸ Á¤È®ÇÑ ±â´ÉÀº ¾Ë·ÁÁ® ÀÖÁö ¾Ê´Ù. ÀÌ ´Ü¹éÁúÀÇ Æ¯Â¡À¸·Î´Â N-¸»´Ü ºÎºÐ¿¡ Æú¸® ±Û·çŸ¹Î ¹Ýº¹¼¿ÀÌ Á¸ÀçÇÏ°í Áß°£¿¡ AXH µµ¸ÞÀΰú C-¸»´Ü ºÎºÐ¿¡ ÀλêÈ°¡ µÇ´Â ¼¼¸° ¾Æ¹Ì³ë»êÀÌ Á¸À縦 Çϴµ¥, AXH µµ¸ÞÀΰú ÀλêÈµÈ ¼¼¸° ¾Æ¹Ì³ë»êÀ» ÅëÇؼ ¿©·¯ Á¾·ùÀÇ °áÇÕ ´Ü¹éÁúµéÀÌ ATXN1 ´Ü¹éÁú°ú »óÈ£ÀÛ¿ëÀ» ÇÑ´Ù°í ¾Ë·ÁÁ® ÀÖ´Ù. ±× °áÇÕ ´Ü¹éÁú Áß, Àü»ç ¾ïÁ¦ ´Ü¹éÁúÀÎ Capicua (CIC)´Â ¼¼Æ÷ÀÇ ÇÙ ¾È¿¡¼ ATXN1ÀÇ AXH µµ¸ÞÀο¡ °áÇÕÇÏ¿© º¹ÇÕü¸¦ Çü¼º ÈÄ, Àü»çÀÇ ÀÌ»óÀ» ÀÏÀ¸ÄÑ Ã´Ãß ¼Ò³ú¼º ¿îµ¿ ½ÇÁ¶Áõ ŸÀÔ1ÀÇ ¹ßº´À» ÀÏÀ¸Å²´Ù°í ¾Ë·ÁÁ® ÀÖ´Ù.
2006³â, ATXN1ÀÇ AXH µµ¸ÞÀΰú CICÀÇ N-¸»´Ü ºÎºÐÀÌ ¼·Î °áÇÕÇÑ´Ù´Â °á°ú°¡ ÀÖ¾ú´Ù(±×¸² 1.a). ÇÏÁö¸¸ ÀÌ º¹ÇÕü°¡ ¼·Î ¾î¶»°Ô »óÈ£ÀÛ¿ëÇÏ´ÂÁö ¾Ë·ÁÁ® ÀÖÁö ¾Ê¾Ò°í, ÀÌ »óÈ£ÀÛ¿ëÀÌ Áúº´ÀÇ ¹ßº´¿¡ ´ëÇÑ ½Ç¸¶¸®¸¦ Á¦°øÇÒ ¼öµµ ÀÖ´Â °¡´É¼ºÀÌ ÀÖ¾ú±â ¶§¹®¿¡, ATXN1 AXH µµ¸ÞÀΰú CICÀÇ º¹ÇÕü¿¡ ´ëÇÑ ±¸Á¶ ½ºÅ͵𸦠ÇÏ°Ô µÇ¾ú´Ù.
±×¸² 1. a. ATXN1°ú CICÀÇ »óÈ£ÀÛ¿ë. b. Ç¥¸éÀüÇϺÐÆ÷µµ·Î ³ªÅ¸³½ ATXN1 AXH µµ¸ÞÀΰú CIC ÆéŸÀ̵å(³ë¶û) º¹ÇÕü ±¸Á¶. b. ATXN1 AXH µµ¸ÞÀÎ(ÆĶû)ÀǼҼö¼º Àܱâµé°ú CIC ÆéŸÀ̵å(³ë¶û)ÀÇ ¼Ò¼ö¼º ÀܱâµéÀÇ »óÈ£ÀÛ¿ë.
±×¸² 2. a. ATXN1 AXH µµ¸ÞÀÎÀÇ µ¿ÁúÀÌÇüü. b. ATXN1 AXH µµ¸ÞÀÎÀÇ N-¸»´Ü ºÎºÐ¿¡ °áÇÕÇÑ CIC ÆéŸÀ̵å(³ë¶û).
±×¸² 3. CICÆéŸÀ̵å(³ë¶û,ÃÊ·Ï)À¸·Î ÀÎÇÑ ATXN1 AXH µµ¸ÞÀÎ- CIC º¹ÇÕüÀÇ(ÆĶû-³ë¶û, »¡°-ÃÊ·Ï) ÀÌÇü»çÇüü Çü¼º.
±×¸² 4. ATXN1 – CIC º¹ÇÕüÀÇ Çü¼º°ú ±¸Á¶ ÀçÇü¼º °úÁ¤
3. ¿¬±¸ÀÇ ¼º°ú ¹× ÀÇÀÇ
ÀÌ ³í¹®¿¡¼´Â ATXN1ÀÇ AXH µµ¸ÞÀΰú CIC ´Ü¹éÁúÀÌ ¼·Î º¹ÇÕü¸¦ Çü¼ºÇÏ°í ´Ù½Ã ±¸Á¶ ÀçÇü¼ºÀ» ÇÑ´Ù´Â °ÍÀ» ±¸Á¶ÀûÀ¸·Î ¹àÈ÷°í, ÀÌ Çö»óÀÌ Ã´Ãß¼Ò³ú¼º ¿îµ¿ ½ÇÁ¶Áõ ŸÀÔ1 Áúº´ÀÇ ¹ßº´À» Á¶ÀýÇÒ ¼ö ÀÖ´Ù´Â °¡´É¼ºÀ» ½Ã»çÇß´Ù. ¶ÇÇÑ Æú¸® ±Û·çŸ¹Î ÅðÇ༺ ³úÁúȯ °ü·Ã ´Ü¹éÁú º¹ÇÕüÀÇ Çü¼º¿¡ ´ëÇÏ¿© ºÐÀÚÇÐÀû, ±¸Á¶ÇÐÀûÀ¸·Î óÀ½ ¹àÇû´Ù´Â ÀÇÀǸ¦ °¡Áø´Ù.
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