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[¹Ì±¹ ͏®Æ÷´Ï¾Æ »÷µð¿¡°í´ëÇÐ(UCSD) ÇÏ¿öµåÈÞºêÀÇÇבּ¸¼ÒÀÇ ÁÖºÀ°Ç ¹Ú»ç(37), ³ú½Å°æ¼¼Æ÷ ºÐÈ­ÀÇ ¿­¼è ã¾Æ³», ½Å°æÁٱ⼼Æ÷°¡ ½Å°æ¼¼Æ÷·Î ºÐÈ­Çϴµ¥ °áÁ¤ÀûÀÎ ¿ªÇÒÀ» ÇÏ´Â ´Ü¹éÁú º¹ÇÕü(Groucho/TLE1 Corepressor Complex) ½Çü ±Ô¸í, ´Ü¹éÁú º¹ÇÕüÀÇ ÀϺÎÀÎ È¿¼Ò(PARP-1)°¡ Ȱµ¿À» Çϸé À¯ÀüÀÚ MASH-1ÀÌ È°¼ºÈ­µÇ ½Å°æ¼¼Æ÷·Î ÀÚ¶ó, ¾ËÃ÷ÇÏÀ̸Ӻ´(±â¾ï»ó½Çº´), ÆÄŲ½¼º´(Áßdz) µî ³ú ¼Õ»ó ȯÀڵ鿡 »õ·Î¿î ½Å°æ¼¼Æ÷ À̽ÄÇÏ¿© Ä¡·áÇÏ´Â ±Ùº» ÇØ°áÃ¥ Á¦½Ã(Activating the PARP-1 Sensor Component of the Groucho/ TLE1 Corepressor Complex Mediates a CaMKinase II¥ä-Dependent Neurogenic Gene Activation Pathway(14/Jan/2005)]

¿ì¸® ³ú(Brain)´Â ¸Å¿ì Áß¿äÇѵ¥, ¸ðµç ±â¾ïÀ̳ª âÀdzª, ÄÄÇ»ÅÍÀÇ Á¤º¸ÀÇ ¼öÁý-ÇØ¼®-ÆíÁý¼öÁ¤-¸í·É-Àü¼ÛÀ» ÇÏ´Â Áß¾ÓÀü»êÀåÄ¡(CPU)ÀÇ ¿ªÇÒÀ» ÇÏ´Â °ÍÀÌ ¹Ù·Î ´º·±(Neuron, ½Å°æ¼¼Æ÷)ÀÌ´Ù. ÀÌ ´º·±ÀÌ °íÀ峪°Å³ª ±î´ß¾øÀÌ Á×À¸¸é ±â¾ï»ó½Çº´(¾ËÃ÷ÇÏÀ̸Ӻ´)À̳ª ÆÄŲ½¼º´(Áßdz)¿¡ °É¸°´Ù.

1. °úÇÐÀÚµéÀÌ ¿¬±¸ÇÏ´Â ´º·±(½Å°æ¼¼Æ÷)ÀÇ ¿µ¿ª

´º·±(½Å°æ¼¼Æ÷)¿¡ °üÇÑÇÑ ¸¹Àº °úÇÐÀÚµéÀÌ ¿¬±¸ÇÏ´Â ¹æÇâÀ» º¸¸é ´ë·« ´ÙÀ½°ú °°Àº ¿©´ü °¡ÁöÀÇ ÁÖÁ¦·Î ¿ä¾àÇÒ ¼ö ÀÖ´Ù. ¸ñÀûÀº °Ç°­À» À¯ÁöÇϰųª º´À» Ä¡·áÇϰí Áö½Ä(Knowledge)À» ¸¹ÀÌ ½ÀµæÇÏ¿© Àß ¸Ô°í ¿À·¡ »ìÀÚ´Â °ÍÀÌ´Ù. ±× ¹æ¹ýÀº Á¤º¸±â¼ú(IT) + ³ª³ë±â¼ú(NT) + ¹ÙÀÌ¿À±â¼ú(BT)ÀÇ À¶ÇÕ(Convergence)·Î °¡´ÉÇÏ´Ù.

1) ½Å°æ¼¼Æ÷´Â ¾î¶² ºÐÈ­°úÁ¤À» °ÅÃÄ ¸¸µé¾îÁö´Â°¡? ÀÌ ¸ÞÄ¿´ÏÁò¸¸ ¹àÇô ³½´Ù¸é Á׾´Â ½Å°æ¼¼Æ÷¸¦ »õ·ÎÀÌ ¸¸µé¾î À̽ÄÇÒ ¼ö ÀÖ´Ù. ÀÌ·¸°Ô µÇ¸é Àå±âÀÌ½Ä -> Á¶Á÷ ÀÌ½Ä -> Áٱ⼼Æ÷ ÀÌ½Ä -> ¼¼Æ÷À̽ÄÀÌ °¡´ÉÇÏ¸ç ¾ðÁ¨°¡´Â À¯ÀüÀÚ À̽ÄÀÌ °¡´ÉÇÑ ½Ã±â°¡ ¿Ã °ÍÀÌ´Ù.

2) ¿ì¸® ¸ö¿¡´Â ´ë·« 1°æ°³ÀÇ ¼¼Æ÷°¡ Á¸ÀçÇÏ´Â °ÍÀ¸·Î ÃßÁ¤µÈ´Ù. ÀÌ 1°æ°³ÀÇ ¼¼Æ÷ Áß ´ë´Ù¼öÀÇ ¼¼Æ÷µéÀº ¼¼Æ÷ ºÐ¿­(Cell division)°ú ¼¼Æ÷ »ç¸ê(Cell death)ÀÌ ¹Ýº¹ÀûÀ¸·Î ÀϾ´Ù. À̸¦ ¼¼Æ÷ÀÇ ÁÖ±â¶ó°í Çϴµ¥, ¿¹¸¦ µé¾î ¸Ó¸®Ä«¶ôÀº ¸¶½ºÅÍÀ¯ÀüÀÚ(Master Gene, À̸¦ Nanog ¶ó ÇÑ´Ù)ÀÇ ¸í·É¿¡ µû¶ó ¸ð±Ù¼¼Æ÷µéÀÌ ºÐ¿­À» °ÅµìÇÏ´Ù°¡ ¼¼Æ÷ »ç¸ê ÇÁ·Î±×·¥¿¡ ÀÇÇØ(À̸¦ Telomere¶ó ÇÑ´Ù) ¹Ýµå½Ã Á״´Ù. ±×·¯¸é ¶Ç ´Ù¸¥ ¸ð±Ù¼¼Æ÷°¡ ºÐ¿­°ú »ç¸êÀ» ¹Ýº¹ÇÑ´Ù. ±×·±µ¥, ÇѰ¡Áö ¿¹¿Ü°¡ ÀÖ´Ù. ´º·±(½Å°æ¼¼Æ÷)´Â »ç¸ê¸¸ ÀÖ´Ù´Â °ÍÀÌ´Ù. ±× ÀÌÀ¯´Â ¹«¾ùÀÌ¸ç ¾î¶² ¸ÞÄ¿´ÏÁòÀ¸·Î »ç¸êÇÏ´ÂÁö ÀÌ °Í¸¸ ¹àÈ÷¸é °ÔÀÓÀº ³¡³ª´Âµ¥, Àý´ëÀÚÀÇ ºñ¹ÐÀ» Ǫ´Â °ÍÀ̱⠶§¹®ÀÌ´Ù.

3) ´º·±Ä¨(½Å°æ¼¼Æ÷ Ĩ)À» °³¹ßÇÏ¿© À̸¦ ȯÀÚ¿¡ À̽ÄÇÏ¸é ±â¾ï»ó½Çº´(¾ËÃ÷ÇÏÀ̸Ӻ´)À̳ª ÆÄŲ½¼º´(Áßdz)À» °íÄ¥ ¼ö ÀÖÀ» »Ó ¾Æ´Ï¶ó, ±â¾ïÀ» º¸°­ÇÒ ¼öµµ ÀÖ°í, ´Ù¸¥ »ç¶÷ÀÇ ±â¾ïÀ̳ª ÄÄÇ»ÅÍ¿¡ ÀúÀåµÈ ¼ö¸¹Àº Á¤º¸µéÀ» ´º·± ĨÀ¸·Î ´Ù¿î ¹ÞÀ» ¼öµµ ÀÖ´Ù. ¾ðÁ¨°¡´Â ¼±Á¶µéÀÌ ÀÌ·èÇØ ³õÀº ¼ö¸¹Àº ¾çÀÇ Áö½ÄÀ» ÇÑ ¼ø°£¿¡ ÇнÀÇÏ°í ±â¾ïÇÒ ¼ö ÀÖÀ» °ÍÀÌ´Ù. ¿µÈ­ MatrixÀÇ Trinityó·³ óÀ½ º¸´Â Ç︮ÄßÅ͸¦ ´º·±À¸·Î ´Ù¿î ¹Þ¾Æ ¸î ÃÊ ¾È¿¡ ÀÍÈú ¼ö ÀÖÀ» °ÍÀÌ´Ù. 

4) ´º·±°ú ´º·±(´º·±Àº +-ÀÇ Àü±â½ÅÈ£·Î Àü¼ÛµÇ¹Ç·Î ÀÌ´Â µðÁöÅÐÀÌ´Ù)À» ¿¬°áÇÏ´Â ½Ã³À½º(Synapse)´Â ´º·±ÀÇ ¸í·É¿¡ µû¶ó ¾Æ³¯·Î±×ÀûÀÎ ¸öÀ» ¿òÁ÷ÀÌ°Ô ÇÏ´Â È­Çй°Áú(½Å°æÀü´Þ¹°Áú, ÀÌ´Â ºÐÀÚÀÌ´Ù)À» ºÐºñÇϴµ¥, ÀÌ ½Ã³À½º°¡ °íÀåÀÌ ³ª¸é ¸öÀÌ ¿òÁ÷ÀÌÁö ¾ÊÀ¸¹Ç·Î ¸¶ºñÀÎ ÆÄŲ½¼º´¿¡ °É¸®´Âµ¥, À̵éÀÇ ¸ÞÄ¿´ÏÁò¸¸ ¹àÇô ³»¸é ÀÌ ¶ÇÇÑ °ÔÀÓÀº ³¡³ª´Â °ÍÀÌ´Ù.

5) °á±¹ ÀÌµé ´º·±°ú ´º·±, ±×¸®°í ½Ã³À½º´Â °Å´ëÇÑ ÀÚÀ²½Å°æ¸Á½Ã½ºÅÛ(ANS, Autonomic Nervous System) À¸·Î ÀÌ·ç¾îÁ® Àִµ¥, ȯÀڵ鿡°Ô ´º·± ĨÀ» À̽ÄÇϰí ÀÌ ÀÚÀ²½Å°æ¸Á½Ã½ºÅÛÀ» Àß ¿¬°áÇϸé, ¼³»ç ÆÈÀÌ ¾ø´õ¶óµµ, ´Ù¸®°¡ ¾ø´õ¶óµµ, µÎ³úÀÇ ¹«¼±¿ø°ÝÁ¶Á¤À¸·Î »ç¹°À̳ª ÄÄÇ»Å͸¦ Á¶ÀÛÇÒ ¼ö ÀÖ´Ù. Áï, »ý°¢¸¸À¸·Î ¶Ç´Â Á¤½ÅÀû Àǵµ(Mental Intentions) ´ë·Î ÄÄÇ»Åͳª ·Îº¿À» Á¶ÀÛÇÒ ¼ö ÀÖ´Ù.

6) ¾ËÃ÷ÇÏÀ̸Ӻ´À̳ª ÆÄŲ½¼º´ µîÀÇ Á¶±â Áø´Ü¿ë ³ª³ë-¹ÙÄÚµå-Áø´ÜºÐ¼®±âÀÇ °³¹ß ¹× ¾Ï¼¼Æ÷¸¸ Á×ÀÌ´Â ³ª³ëº¿(Nanobot) ¶Ç´Â ³ª³ë ĸ½¶ µîÀÇ °³¹ßÀÌ´Ù. ÀÌ´Â ³úÀÇ º´À» Á¶±â¿¡ Áø´Ü(Diagnostic)-ºÐ¼®(Analysis)-ó¹æ(Treatment)-¿¹¹æ(Preventive) ¹× º´ÀÇ ¿¹ÈÄ(º´ÀÇ °æ°ú³ª °á¸»ÀÇ ¿¹»ó, Prognostic)¿¡ °ü·ÃµÈ ±â¼úµéÀÌ´Ù.

7) ´º·±¼¼Æ÷ÀÇ ¸ÞÄ¿´ÏÁòÀ» ¹àÇô ´º·± ÄÄÇ»ÆÃ, DNA ÄÄÇ»ÆÃ ¶Ç´Â ´º·± ºÐÀÚ ÄÄÇ»ÆÃÀ» ¸¸µéÀÚ´Â °ÍÀÌ¿ä, ½Ã³À½ºÀÇ ¸ÞÄ¿´ÏÁòÀ» ¹àÇô ºÐÀÚ Á¦Á¶±â(Molecular Assembler, Personal Fab)À» ¸¸µéÀÚ´Â °ÍÀÌ´Ù.

8) À§ÀÇ ¸ðµç ¸ÞÄ¿´ÏÁòÀÌ ¹àÇôÁö°í ±â¼úÀÌ °³¹ßµÇ¸é Àΰ£À» »õ·ÎÀÌ ¸¸µéÀÚ´Â °ÍÀÌ´Ù. Áï, Àΰ£À» º¹Á¦(Human cloning)¿¡ µµÀüÇÏÀÚ´Â °ÍÀÌ´Ù. Àý´ëÀÚ°¡ ÀÚ±âÀÇ Çü»ó´ë·Î Àΰ£À» ¸¸µé¾úµíÀÌ Àΰ£µµ Àΰ£ÀÇ Çü»ó´ë·Î ´Ù¸¥ Àΰ£À» ¸¸µéÀÚ´Â °ÍÀÌ´Ù.

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[¿µ±¹ ¿¡µç¹ö·¯ ´ëÇÐ ¿À½ºÆ¾ ½º¹Ì½º(Austin Smith) ±³¼ö¿Í ÀϺ» ³ª¶ó °úÇбâ¼ú¿¬±¸¼Ò ¾ß¸¶³ªÄ« ½Å¾ß(Shinya Yamanaka) ¹Ú»ç, ÄÌÆ®Á· Àü¼³ÀÇ ¡®ºÒ»ç(ÜôÞÝ)ÀÇ ¶¥¡¯À» ÀǹÌÇÏ´Â ¡®³ª³ë±×(Nanog)¡¯¶ó´Â ¸¶½ºÅÍ À¯ÀüÀÚ(Master Gene) ¹ß°ß - Áٱ⠼¼Æ÷·Î ½ÉÀå-°£-ÇǺΠµîÀÇ Àå±â(±â°ü)¿Í Á¶Á÷ ¸¸µé¾î ºÒÄ¡º´ ÇØ°á¿¡ ȹ±âÀûÀÎ ½Ç¸¶¸® Á¦°ø - ÀÌ À¯ÀüÀÚ¸¸ ÅëÁ¦ÇÒ ¼ö ÀÖ´Ù¸é ±Ø´ÜÀûÀÎ °æ¿ì Áٱ⠼¼Æ÷°¡ ¾Æ´Ñ ÀÏ¹Ý ¼¼Æ÷·Îµµ Àå±â¿Í Á¶Á÷À» ¸¸µé ¼ö ÀÖ°Ô µÈ´Ù. À¯ÀüÇÐÀÚµéÀÌ ¿À·£ ½Ã°£ µ¿¾È ã¾Æ Çì¸Å´ø ¡®»ý¹°ÇÐÀÇ ¼º¹è(á¡ÛÊ)¡¯¸¦ ¹ß°ßÇÑ °Í°ú °°Àº Àǹ̸¦ °®´Â´Ù°í ³íÆò, ±×·¯³ª ¾ÆÁ÷ ¸Ö¾î(2003³â 5¿ù 29ÀÏ)]
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2. ÁÖºÀ°Ç ¹Ú»ç - ½Å°æ¼¼Æ÷ ºÐÈ­ÀÇ ¸ÞÄ¿´ÏÁò ¹àÇô³»

ÀÌÁß ¿À´Ã ¼Ò°³ÇÏ´Â ³»¿ëÀº ù¹øÂ° ¿µ¿ª ÁÖÁ¦ÀÎ ½Å°æ¼¼Æ÷ÀÇ ºÐÈ­ ¸ÞÄ¿´ÏÁò¿¡ µµÀüÇÏ´Â ³»¿ëÀ¸·Î, ³ú ¼Ó¿¡ ÀÖ´Â ½Å°æÁٱ⼼Æ÷°¡ ´Ù¾çÇÑ Á¾·ùÀÇ ½Å°æ¼¼Æ÷(´º·±)·Î ºÐÈ­Çϴµ¥ °áÁ¤ÀûÀÎ ¿ªÇÒÀ» ÇÏ´Â ´Ü¹éÁúÀÇ ½Çü¸¦ Çѱ¹ÀÎ °úÇÐÀÚ°¡ óÀ½ ±Ô¸íÇß´Ù´Â °ÍÀÌ´Ù.

¹Ì±¹ »÷µð¿¡À̰í ͏®Æ÷´Ï¾Æ´ë(UCSD, University of California, San Diego) Àǰú´ë(Department and School of Medicine)ÀÇ HHMI ¿¬°è ÇÏ¿öµåÈÞÁîÀÇÇבּ¸¼Ò(Howard Hughes Medical Institute)ÀÇ ÁÖºÀ°Ç ¹Ú»ç(37·»çÁø) ¿¬±¸ÆÀÀº 2004³â 12¿ù 19ÀÏ »ýÁ㠽ŰæÁٱ⼼Æ÷ÀÇ ¼ºÀåÀÌ ¾ïÁ¦µÇ°Å³ª ÃËÁøµÇ´Â »ó¹ÝµÈ ÀÛ¿ëÀÌ µ¿ÀÏÇÑ ¡®´Ü¹éÁú º¹ÇÕü(Groucho/TLE1 Corepressor Complex)¡¯¿¡ ÀÇÇØ ÀÌ·ïÁø´Ù´Â Á¡À» ¹ß°ßÇß´Ù°í ¹àÇû´Ù. ÀÌ ¿¬±¸³í¹®Àº »ý¹°ÇÐ ÃÖ°íÀÇ ±ÇÀ§Áö ¡®¼¿(Cell)¡¯ÀÇ 2004³â 12¿ù 17ÀÏÀÚ¿¡ °ÔÀçµÆ´Ù. ½Å°æÁٱ⼼Æ÷´Â ƯÁ¤ ½ÅÈ£¸¦ ¹ÞÀ¸¸é À¯ÀüÀÚ(MASH-1)°¡ Ȱ¼ºÈ­µÅ ½Å°æ¼¼Æ÷·Î ÀÚ¶õ´Ù. ±×µ¿¾È MASH-1ÀÇ ±â´ÉÀº ´Ü¹éÁú º¹ÇÕü¿¡ ÀÇÇØ ¾ïÁ¦µÇ´Â °ÍÀ¸·Î ¾Ë·ÁÁ® ÀÖ¾ú´Ù.

 ¿¬±¸ÆÀÀº ´Ü¹éÁú º¹ÇÕüÀÇ °¨Áö¿ä¼Ò(Sensor Component)ÀÎ PARP-1(poly(ADP-ribose) polymerase1) À̶ó´Â È¿¼Ò°¡ Ȱµ¿À» ½ÃÀÛÇϸé À¯ÀüÀÚ MASH-1ÀÌ È°¼ºÈ­µÅ ½Å°æÁٱ⼼Æ÷ÀÇ ºÐÈ­°¡ ÀÌ·ïÁø´Ù´Â Á¡À» óÀ½ ¹àÇû´Ù.

ÁÖ ¹Ú»ç´Â µ¿¾ÆÀϺ¸¿ÍÀÇ ÀüÈ­ÅëÈ­¿¡¼­ ¡°À̹ø ¿¬±¸ °á°ú´Â ¾ËÃ÷ÇÏÀ̸Ӻ´À̳ª ÆÄŲ½¼º´ µî ³ú ¼Õ»ó ȯÀÚµéÀÇ Ä¡·á¿¡ ±Ùº»ÀûÀÎ ÇØ°áÃ¥À» Á¦½ÃÇÑ °Í¡±À̶ó°í ¸»Çß´Ù. ȯÀڷκÎÅÍ ½Å°æÁٱ⼼Æ÷¸¦ ¾ò¾î PARP-1ÀÇ ±â´ÉÀ» Ȱ¼ºÈ­½ÃŰ¸é °Ç°­ÇÑ ½Å°æ¼¼Æ÷·Î ÀÚ¶ö ¼ö ÀÖ´Ù´Â ¾ê±âÀÌ´Ù.
ÀÌ ½Å°æ¼¼Æ÷¸¦ ´Ù½Ã ȯÀÚÀÇ ³ú¿¡ À̽ÄÇÑ´Ù¸é È¿°úÀûÀÎ Ä¡·á°¡ °¡´ÉÇÏ´Ù´Â ¼³¸íÀÌ´Ù.


[Cell Áö °ÔÀç ³í¹®]

 

 

 

* ³í¹® ŸÀÌÆ² :

 

Activating the PARP-1 Sensor Component of the Groucho/ TLE1 Corepressor Complex Mediates a CaMKinase II¥ä-Dependent Neurogenic Gene Activation Pathway

* °Ô   Àç    ÀÏ : 

Cell, Vol 119, 815-829, 17 December 2004

* Àú          ÀÚ :
 

Bong-Gun Ju, Derek Solum, Eun Joo Song, Kong-Joo Lee, David W. Rose, Christopher K. Glass, and Michael G. Rosenfeld

* ¿ä          ¾à :

[Summary]

* ¿ä          ¾à :

Switching specific patterns of gene repression and activation in response to precise temporal/spatial signals is critical for normal development. Here we report a pathway in which induction of CaMKII¥ä triggers an unexpected switch in the function of the HES1 transcription factor from a TLE-dependent repressor to an activator required for neuronal differentiation. These events are based on activation of the poly(ADP-ribose) polymerase1 (PARP-1) sensor component of the groucho/TLE-corepressor complex mediating dismissal of the corepressor complex from HES1-regulated promoters. In parallel, CaMKII¥ä mediates a required phosphorylation of HES1 to permit neurogenic gene activation, revealing the ability of a specific signaling pathway to modulate both the derepression and the subsequent coactivator recruitment events required for transcriptional activation of a neurogenic program. The identification of PARP-1 as a regulated promoter-specific exchange factor required for activation of specific neurogenic gene programs is likely to be prototypic of similar molecular mechanisms.

* ¿¬   ¶ô    Ã³ : Michael G. Rosenfeld
858-534-5858 (phone)
858-534-8180 (fax)
mrosenfeld@ucsd.edu

Bong-Gun Ju
bju@ucsd.edu

[¼Ò½º]
[µ¿¾ÆÀϺ¸ - ÁÖºÀ°Ç ¹Ú»ç, ³ú½Å°æ¼¼Æ÷ ¡®ºÐÈ­ÀÇ ¿­¼è¡¯ ã¾Æ³», ¼­¿ï´ë À±º´¿ì ±³¼ö, ÀÎüÁٱ⼼Æ÷·Î ¡®³ú°æ»ö Á㡯 Ä¡·á(19/Dec/2004)]
[µ¿¾ÆÀϺ¸ - ³ú Áٱ⼼Æ÷ ºÐÈ­ÀÇ ºñ¹Ð, Çѱ¹ÀÎÀÌ ±Ô¸í(19/Dec/2004)]

Ű¿öµå : UCSD, ÁÖºÀ°Ç ¹Ú»ç(37), ³ú½Å°æ¼¼Æ÷ ºÐÈ­, ½Å°æÁٱ⼼Æ÷°¡ ½Å°æ¼¼Æ÷·Î ºÐÈ­, ´Ü¹éÁú º¹ÇÕü(Groucho/TLE1 Corepressor Complex), È¿¼Ò(PARP-1), À¯ÀüÀÚ MASH-1, ¾ËÃ÷ÇÏÀ̸Ӻ´(±â¾ï»ó½Çº´), ÆÄŲ½¼º´(Áßdz), Activating the PARP-1 Sensor Component of the Groucho/ TLE1 Corepressor Complex Mediates a CaMKinase II¥ä-Dependent Neurogenic Gene Activation Pathway, ´º·±(½Å°æ¼¼Æ÷),  HHMI, ÇÏ¿öµåÈÞÁîÀÇÇבּ¸¼Ò(Howard Hughes Medical Institute)