{"id":1372,"date":"2024-11-12T13:46:30","date_gmt":"2024-11-12T05:46:30","guid":{"rendered":"https:\/\/www.huanglab.org.cn\/wordpress\/?p=1372"},"modified":"2024-11-12T13:46:30","modified_gmt":"2024-11-12T05:46:30","slug":"cell-%e9%9f%a9%e9%9c%86%e5%ae%9e%e9%aa%8c%e5%ae%a4%e4%b8%8e%e9%bb%84%e7%89%9b%e5%ae%9e%e9%aa%8c%e5%ae%a4%e5%90%88%e4%bd%9c%e5%bc%80%e5%8f%91%e5%a4%9a%e8%81%9a%e8%9b%8b%e7%99%bd%e9%80%89%e6%8b%a9","status":"publish","type":"post","link":"https:\/\/www.huanglab.org.cn\/wordpress\/?p=1372","title":{"rendered":"Cell | \u97e9\u9706\u5b9e\u9a8c\u5ba4\u4e0e\u9ec4\u725b\u5b9e\u9a8c\u5ba4\u5408\u4f5c\u5f00\u53d1\u591a\u805a\u86cb\u767d\u9009\u62e9\u6027\u964d\u89e3\u6280\u672f"},"content":{"rendered":"\n
\"\u672c\u6587\u7684\u5171\u540c\u7b2c\u4e00\u4f5c\u8005\u4e4b\u4e00\uff0c\u4efb\u6b23\u6850\"<\/a>
\u4efb\u6b23\u6850\uff0c\u5171\u540c\u7b2c\u4e00\u4f5c\u8005\u4e4b\u4e00<\/figcaption><\/figure>\n\n\n\n

\u901a\u8fc7\u5316\u5b66\u5c0f\u5206\u5b50\u8bf1\u5bfc\u9776\u86cb\u767d\u548cE3\u6cdb\u7d20\u8fde\u63a5\u9176\u7684\u76f8\u4e92\u4f5c\u7528\uff0c\u4ece\u800c\u5b9e\u73b0\u9776\u86cb\u767d\u7684\u7279\u5f02\u6027\u964d\u89e3\u662f\u4e00\u79cd\u65b0\u5174\u7684\u836f\u7269\u5f00\u53d1\u6a21\u5f0f\uff0c\u4e3a\u4f20\u7edf\u4e0a\u88ab\u8ba4\u4e3a\u201c\u96be\u4ee5\u6210\u836f\u201d\u7684\u9776\u70b9\u63d0\u4f9b\u4e86\u5168\u65b0\u7684\u89e3\u51b3\u65b9\u6848\u3002\u5f53\u524d\u7528\u4e8e\u9776\u5411\u86cb\u767d\u964d\u89e3\u7684\u5316\u5b66\u5206\u5b50\u4e3b\u8981\u5206\u4e3a\u4e24\u7c7b\uff1a\u86cb\u767d\u964d\u89e3\u9776\u5411\u5d4c\u5408\u4f53(PROTAC)\u548c\u5206\u5b50\u80f6(Molecular Glue)\u3002PROTAC\u662f\u4e00\u7c7b\u53cc\u529f\u80fd\u5206\u5b50\uff0c\u7531\u9776\u86cb\u767d\u7ed3\u5408\u914d\u4f53\u3001E3\u6cdb\u7d20\u8fde\u63a5\u9176\u7ed3\u5408\u914d\u4f53\u4ee5\u53ca\u8fde\u63a5\u5b50\u7ec4\u6210\u3002\u8fd1\u671f\u5df2\u6709\u591a\u4e2aPROTAC\u5206\u5b50\u8fdb\u5165\u4e34\u5e8a\u8bd5\u9a8c\uff0c\u5e76\u5728\u4eba\u7c7b\u60a3\u8005\u4e2d\u9a8c\u8bc1\u4e86\u5176\u7597\u6548\u4e0e\u5b89\u5168\u6027\u3002\u5206\u5b50\u80f6\u5219\u662f\u4e00\u7c7b\u5355\u4ef7\u5206\u5b50\uff0c\u901a\u8fc7\u4f5c\u7528\u4e8e\u86cb\u767d-\u86cb\u767d\u7684\u76f8\u4e92\u4f5c\u7528\u754c\u9762\uff0c\u589e\u5f3aE3\u6cdb\u7d20\u8fde\u63a5\u9176\u4e0e\u9776\u86cb\u767d\u4e4b\u95f4\u7684\u76f8\u4e92\u4f5c\u7528\u3002\u4ee3\u8868\u6027\u7684\u5206\u5b50\u80f6\u836f\u7269\u6765\u90a3\u5ea6\u80fa\u548c\u6cca\u9a6c\u5ea6\u80fa\u5728\u6cbb\u7597\u591a\u53d1\u6027\u9aa8\u9ad3\u7624\u4e2d\u5c55\u73b0\u51fa\u4e86\u663e\u8457\u7597\u6548\u3002\u6b64\u5916\uff0c\u97e9\u9706\u56e2\u961f\u524d\u671f\u53d1\u73b0\u7684\u82b3\u57fa\u78fa\u80fa\u7c7b\u5206\u5b50(Han et al., Science 2017)\u548cHQ461(Lv et al., eLife 2020)\u4e5f\u5177\u6709\u5206\u5b50\u80f6\u6d3b\u6027\uff1b\u8fd9\u4e24\u7c7b\u5206\u5b50\u80f6\u7684\u53d1\u73b0\u8fdb\u4e00\u6b65\u62d3\u5bbd\u4e86\u5206\u5b50\u80f6\u7684\u5e94\u7528\u8303\u56f4\u3002\u867d\u7136PROTAC\u548c\u5206\u5b50\u80f6\u836f\u7269\u5f00\u53d1\u53d6\u5f97\u4e86\u663e\u8457\u8fdb\u5c55\uff0c\u4f46\u662f\u9776\u5411\u86cb\u767d\u964d\u89e3\u9886\u57df\u4e3b\u8981\u4f9d\u8d56\u4e8eCRBN\u6216VHL\u7b49\u5e7f\u6cdb\u8868\u8fbe\u4e14\u6301\u7eed\u6d3b\u8dc3\u7684E3\u6cdb\u7d20\u8fde\u63a5\u9176\uff0c\u5728\u533a\u5206\u6b63\u5e38\u86cb\u767d\u548c\u81f4\u75c5\u86cb\u767d\u65b9\u9762\uff0c\u73b0\u6709\u6280\u672f\u5c1a\u5b58\u5728\u4e0d\u8db3\u3002\u56e0\u6b64\uff0c\u53d1\u73b0\u80fd\u591f\u9009\u62e9\u6027\u964d\u89e3\u81f4\u75c5\u86cb\u767d\u7684E3\u6cdb\u7d20\u8fde\u63a5\u9176\u53ca\u5176\u914d\u4f53\u81f3\u5173\u91cd\u8981\u3002<\/p>\n\n\n\n

2024\u5e7411\u67081\u65e5\uff0c\u5317\u4eac\u751f\u547d\u79d1\u5b66\u7814\u7a76\u6240\/\u6e05\u534e\u5927\u5b66\u751f\u7269\u533b\u5b66\u4ea4\u53c9\u7814\u7a76\u9662\u97e9\u9706\u5b9e\u9a8c\u5ba4\u4e0e\u9ec4\u725b\u5b9e\u9a8c\u5ba4\u5728\u300aCell\u300b\u4e0a\u5728\u7ebf\u53d1\u8868\u4e86\u9898\u4e3a\u201cSelective degradation of multimeric proteins by TRIM21-based molecular glue and PROTAC degraders\u201d\u7684\u7814\u7a76\u8bba\u6587\u3002\u8be5\u7814\u7a76\u53d1\u73b0\u4e59\u9170\u4e19\u55ea\u7684\u4ee3\u8c22\u4ea7\u7269(S)-ACE-OH\u5177\u6709E3\u6cdb\u7d20\u8fde\u63a5\u9176TRIM21\u4ecb\u5bfc\u7684\u5206\u5b50\u80f6\u6d3b\u6027\uff0c\u5e76\u636e\u6b64\u8bbe\u8ba1\u4e86\u57fa\u4e8eTRIM21\u7684\u65b0\u578bPROTAC\u5206\u5b50(\u547d\u540d\u4e3aTrimTAC)\uff0c\u80fd\u591f\u9009\u62e9\u6027\u964d\u89e3\u591a\u805a\u86cb\u767d\u800c\u4e0d\u5f71\u54cd\u5355\u4f53\u86cb\u767d\u3002\u7531\u4e8e\u5f02\u5e38\u86cb\u767d\u805a\u96c6\u4f1a\u5f15\u53d1\u81ea\u8eab\u514d\u75ab\u75be\u75c5\u3001\u795e\u7ecf\u9000\u884c\u6027\u75be\u75c5\u4ee5\u53ca\u764c\u75c7\uff0c\u4e0a\u8ff0\u7814\u7a76\u6210\u679c\u7a81\u663e\u51faTrimTAC\u6280\u672f\u7684\u5e94\u7528\u524d\u666f\u3002<\/p>\n\n\n\n

\u7814\u7a76\u4eba\u5458\u9996\u5148\u901a\u8fc7\u57fa\u4e8e\u8868\u578b\u7684\u9ad8\u901a\u91cf\u7b5b\u9009\u53d1\u73b0\u4e86\u4e59\u9170\u4e19\u55ea(ACE)\u80fd\u4e0e\u5e72\u6270\u7d20\u534f\u540c\u6740\u4f24\u975e\u5c0f\u7ec6\u80de\u80ba\u764c\u7ec6\u80de\u7cfbA549\u3002\u4f7f\u7528\u4e59\u9170\u4e19\u55ea\u5904\u7406\u591a\u79cd\u80bf\u7624\u7ec6\u80de\u7cfb\u548c\u6b63\u5e38\u7ec6\u80de\uff0c\u53d1\u73b0\u4e59\u9170\u4e19\u55ea\u5bf9\u90e8\u5206\u80bf\u7624\u7ec6\u80de\u7cfb\u9009\u62e9\u6027\u6740\u4f24\uff0c\u4f46\u4e0d\u5f71\u54cd\u53e6\u4e00\u4e9b\u80bf\u7624\u7ec6\u80de\u7cfb\u4ee5\u53ca\u6b63\u5e38\u7ec6\u80de\u3002\u8fdb\u4e00\u6b65\u7814\u7a76\u53d1\u73b0\uff0cACE\u654f\u611f\u7ec6\u80de\u7cfb\u901a\u8fc7\u919b\u916e\u8fd8\u539f\u9176\u5c06ACE\u8fd8\u539f\u6210\u4e86S\u6784\u578b\u7684\u7f9f\u4e59\u57fa\u4e19\u55ea(ACE-OH)\uff0c\u800c(S)-ACE-OH\u662f\u6740\u4f24\u80bf\u7624\u7ec6\u80de\u7684ACE\u4ee3\u8c22\u4ea7\u7269\u3002<\/p>\n\n\n\n

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TRIM21\u662f\u4e00\u79cd\u5148\u5929\u514d\u75ab\u53d7\u4f53\uff0c\u53ef\u8bc6\u522b\u9003\u9038\u5230\u7ec6\u80de\u8d28\u5185\u5e76\u4e14\u88ab\u6297\u4f53\u5305\u88ab\u7684\u75c5\u6bd2\uff0c\u4ece\u800c\u89e6\u53d1\u6297\u75c5\u6bd2\u514d\u75ab\u53cd\u5e94\u3002TRIM21\u7684C\u7aefPRYSPRY\u7ed3\u6784\u57df\u5177\u6709\u4e00\u4e2a\u758f\u6c34\u53e3\u888b\uff0c\u53ef\u7ed3\u5408\u6297\u4f53\u7684Fc\u533a\u3002\u7814\u7a76\u4eba\u5458\u5728TRIM21\u7684Fc\u7ed3\u5408\u53e3\u888b\u4e2d\u6784\u5efa\u4e86\u51e0\u4e2a\u70b9\u7a81\u53d8\uff0c\u53d1\u73b0W381A\u6216W383A\u7a81\u53d8\u5b8c\u5168\u963b\u65ad\u4e86\u4e59\u9170\u4e19\u55ea\u7684\u6d3b\u6027\uff0c\u800cD355A\u7a81\u53d8\u5219\u589e\u5f3a\u4e86\u4e59\u9170\u4e19\u55ea\u7684\u654f\u611f\u6027\uff0c\u4e0a\u8ff0\u7ed3\u679c\u8868\u660eTRIM21\u4e0eFc\u7ed3\u5408\u7684\u53e3\u888b\u5f88\u53ef\u80fd\u4e5f\u662f(S)-ACE-OH\u7ed3\u5408\u7684\u4f4d\u70b9\u3002<\/p>\n\n\n\n

\u7531\u4e8eTRIM21\u5177\u6709E3\u6cdb\u7d20\u8fde\u63a5\u9176\u6d3b\u6027\uff0c\u7814\u7a76\u4eba\u5458\u901a\u8fc7\u5b9a\u91cf\u8d28\u8c31\u5b9e\u9a8c\u53d1\u73b0(S)-ACE-OH\u53ef\u4ee5\u8bf1\u5bfcNUP35\u3001SMPD4\u548cGLE1\u7b49\u591a\u4e2a\u6838\u5b54\u86cb\u767d\u7684\u964d\u89e3\uff0c\u4ece\u800c\u7834\u574f\u4e86\u6838\u5b54\u7ed3\u6784\uff0c\u9020\u6210\u6838\u8d28\u4e3b\u52a8\u8f6c\u8fd0\u529f\u80fd\u7684\u4e27\u5931\u3002\u4e3a\u4e86\u63a2\u7a76\u6838\u5b54\u590d\u5408\u7269\u4e0aTRIM21\u76f4\u63a5\u7684\u4f5c\u7528\u9776\u70b9\uff0c\u7814\u7a76\u4eba\u5458\u8fdb\u884c\u4e86CRISPR-suppressor scanning\u548cPML-degron\u878d\u5408\u86cb\u767d\u964d\u89e3\u5b9e\u9a8c\uff0c\u5c06\u6838\u5b54\u590d\u5408\u7269\u4e0a\u7684\u9776\u70b9\u951a\u5b9a\u5230\u4e86NUP98\u3002\u7814\u7a76\u4eba\u5458\u8fdb\u4e00\u6b65\u4f7f\u7528GST pulldown\u548cITC\u5b9e\u9a8c\u5728\u4f53\u5916\u91cd\u6784\u4e86(S)-ACE-OH\u3001TRIM21\u548cNUP98\u7684\u4e09\u5143\u590d\u5408\u7269\uff0c\u4ece\u800c\u8bc1\u660e (S)-ACE-OH\u662f\u4e00\u79cd\u5168\u65b0\u7684\u5206\u5b50\u80f6\u3002<\/p>\n\n\n\n

\u7814\u7a76\u4eba\u5458\u901a\u8fc7X\u5c04\u7ebf\u6676\u4f53\u884d\u5c04\u83b7\u5f97\u4e86\u4e59\u9170\u4e19\u55ea\u53ca\u5176\u4ee3\u8c22\u4ea7\u7269\u4e0eTRIM21\u7684\u5171\u6676\u7ed3\u6784\uff0c\u4e3a\u65b0\u914d\u4f53\u7684\u5f00\u53d1\u548cPROTAC\u7684\u8bbe\u8ba1\u63d0\u4f9b\u4e86\u65b9\u5411\u3002\u6839\u636e\u6676\u4f53\u7ed3\u6784\u8bbe\u8ba1\u4e86\u57fa\u4e8eTRIM21\u7684PROTAC\uff08\u547d\u540d\u4e3aTrimTAC\uff09\u3002\u901a\u8fc7\u5bf9\u6bd4TrimTAC\u548c\u4f20\u7edf\u7684\u57fa\u4e8eCRBN\u7684PROTAC\u7684\u7ec6\u80de\u6d3b\u6027\uff0c\u53d1\u73b0TrimTAC\u4e0d\u80fd\u964d\u89e3\u5355\u4f53\u86cb\u767d\uff0c\u4f46\u80fd\u964d\u89e3\u805a\u96c6\u5f62\u5f0f\u7684\u86cb\u767d\uff1b\u800c\u57fa\u4e8eCRBN\u7684PROTAC\u4e0d\u5177\u5907\u4e0a\u8ff0\u9009\u62e9\u6027\u3002\u8fd9\u4e00\u7279\u6027\u6765\u6e90\u4e8eTRIM21\u7684\u672c\u8eab\u6027\u8d28\uff1a\u4e0e\u591a\u805a\u7684\u9776\u86cb\u767d\u7ed3\u5408\u540e\uff0cTRIM21\u7684RING\u7ed3\u6784\u57df\u4e8c\u805a\uff0c\u624d\u80fd\u6fc0\u6d3b\u5176E3\u6cdb\u7d20\u8fde\u63a5\u9176\u7684\u6d3b\u6027\u3002\u4e3a\u4e86\u9a8c\u8bc1TrimTAC\u5728\u75be\u75c5\u6cbb\u7597\u65b9\u9762\u7684\u5e94\u7528\u524d\u666f\uff0c\u7814\u7a76\u4eba\u5458\u4f7f\u7528TrimTAC\u5b9e\u73b0\u4e86\u80de\u8d28DNA\u8bf1\u5bfc\u7684cGAS\u805a\u96c6\u4f53\u7684\u9009\u62e9\u6027\u964d\u89e3\uff0c\u4ece\u800c\u4e3aTrimTAC\u6cbb\u7597\u81ea\u8eab\u514d\u75ab\u6027\u75be\u75c5\u63d0\u4f9b\u4e86\u6f5c\u5728\u5e94\u7528\u573a\u666f\u3002<\/p>\n\n\n\n

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\u57fa\u4e8eTRIM21\u7684\u5206\u5b50\u80f6\u548cPROTAC\u7684\u4f5c\u7528\u673a\u7406\u4ee5\u53ca\u672a\u6765\u7684\u5e94\u7528\u65b9\u5411<\/p>\n\n\n\n

\"\"<\/a><\/figure>\n\n\n\n

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\u8bba\u6587\u94fe\u63a5<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

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