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 <\/p>\n

\"1\"<\/section>\n
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<\/section>\n
\u5173\u952e\u6570\u636e\uff1a<\/strong><\/section>\n
1.HaloMap\u6355\u83b7SG\u86cb\u767d\u7ec4<\/strong>\u00a0 \u00a0<\/section>\n
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\"2\"<\/section>\n
\u56fe1 HaloMap\u65b9\u6cd5\u7684\u793a\u610f\u56fe\u3002\u00a0 \u00a0<\/section>\n
\u00a0 \u00a0 \u00a0 \u00a0 \u00a0\u00a0<\/section>\n
2.HaloMap\u65b9\u6cd5\u9274\u5b9a\u6cdb\u7d20\u4ecb\u5bfc\u7684SG\u89e3\u805a\u901a\u8def<\/strong><\/section>\n
\u5728\u5efa\u7acb\u4e86HaloMap\u6807\u8bb0\u5e73\u53f0\u540e\uff0c\u4f5c\u8005\u63a5\u4e0b\u6765\u8bd5\u56fe\u5206\u6790SG\u89e3\u805a\u8fc7\u7a0b\u4e2d\u53d1\u751f\u7684\u86cb\u767d\u7ec4\u5b66\u53d8\u5316\uff0c\u4ee5\u6355\u6349\u53ef\u80fd\u7684\u5173\u952e\u8c03\u8282\u56e0\u5b50\u3002SG\u5728\u65b0\u9c9c\u57f9\u517b\u57fa\u4e2d\u7ea62\u5c0f\u65f6\u540e\u5b8c\u5168\u89e3\u805a\uff08\u56fe2a\uff09\u3002\u57fa\u4e8e\u8fd9\u4e9b\u52a8\u6001\u5b66\uff0c\u4f5c\u8005\u5728\u53bb\u9664AS\u540e\u768430\u5206\u949f\uff08D30\uff09\u300160\u5206\u949f\uff08D60\uff09\u548c120\u5206\u949f\uff08D120\uff09\u8fdb\u884cHaloMap\u6807\u8bb0\uff0c\u4ee5\u4ee3\u8868\u89e3\u805a\u8fc7\u7a0b\u7684\u65e9\u671f\u3001\u4e2d\u671f\u548c\u665a\u671f\uff08\u56fe2b\uff09\u3002\u4ece\u6bcf\u4e2a\u65f6\u95f4\u70b9\u7684HaloTag-G3BP1\u4e0eHaloTag-NES\u6807\u8bb0\u6bd4\u8f83\u4e2d\uff0c\u9274\u5b9a\u5230698\u4e2aSG\u76f8\u4e92\u4f5c\u7528\u86cb\u767d\u6c34\u5e73\u53d8\u5316\u3002\u968f\u7740\u9897\u7c92\u7684\u89e3\u805a\uff0c\u5927\u7ea670%\u7684\u9897\u7c92\u76f8\u4e92\u4f5c\u7528\u86cb\u767d\u7684\u5bcc\u96c6\u968f\u7740\u6062\u590d\u800c\u964d\u4f4e\uff08\u56fe2c\uff09\u3002\u7136\u800c\uff0c\u4f5c\u8005\u5bf9\u4e00\u7ec4\u5728\u6062\u590d\u671f\u95f4\u5448\u73b0\u51fa\u589e\u52a0\u5173\u8054\u7684\u86cb\u767d\u8d28\uff08n=203\uff09\u7684\u51fa\u73b0\u611f\u5230\u5174\u8da3\uff0c\u56e0\u4e3a\u8fd9\u4e9b\u53ef\u80fd\u662f\u9897\u7c92\u89e3\u805a\u7684\u8c03\u63a7\u86cb\u767d\u3002GO\u5206\u6790\u663e\u793a\u51fa\u660e\u663e\u5bcc\u96c6\u7684\u86cb\u767d\u8d28\uff0c\u4e3b\u8981\u662f\u6b63\u5411\u8c03\u8282\u6216\u542f\u52a8\u7ffb\u8bd1\u7684\u86cb\u767d\u8d28\uff0c\u5373\u968f\u7740\u7ec6\u80de\u4ece\u5e94\u6fc0\u4e2d\u6062\u590d\uff0cmRNA\u4ece\u9897\u7c92\u7684\u91ca\u653e\u548c\u7ffb\u8bd1\u3002\u6b64\u5916\uff0c\u591a\u4e2a\u4e0e\u6cdb\u7d20\u5316\u548c\u86cb\u767d\u8d28\u8d28\u91cf\u63a7\u5236\u9014\u5f84\u76f8\u5173\u7684\u86cb\u767d\u8d28\u4e5f\u663e\u793a\u51fa\u5bcc\u96c6\uff08\u56fe2c\uff09\u3002\u63a5\u4e0b\u6765\uff0c\u901a\u8fc7\u514d\u75ab\u8367\u5149\uff0c\u4f5c\u8005\u89c2\u5bdf\u5230\u5728\u5e94\u6fc0\u5904\u7406\u540e\uff0c\u6cdb\u7d20\u4fe1\u53f7\u4e0eG3BP1\/\u9897\u7c92\u7684\u5f3a\u91cd\u53e0\uff0c\u8fd9\u8868\u660e\u8fd9\u4e9b\u51dd\u805a\u7269\u542b\u6709\u591a\u6cdb\u7d20\u5316\u7684\u86cb\u767d\u3002\u6b64\u5916\uff0c\u4f5c\u8005\u786e\u8ba4\u5728\u5e94\u6fc0\u548c\u65e9\u671f\u6062\u590d\u65f6\uff08\u5e94\u6fc0\u540e30\u5206\u949f\uff09\u6574\u4f53\u591a\u6cdb\u7d20\u6c34\u5e73\u7684\u4e0a\u8c03\uff08\u56fe2e\uff09\u3002\u4e3a\u4e86\u8fdb\u4e00\u6b65\u4e86\u89e3\u6cdb\u7d20\u5316\u5bf9\u9897\u7c92\u52a8\u529b\u5b66\u7684\u5f71\u54cd\uff0c\u4f5c\u8005\u63a5\u4e0b\u6765\u6d4b\u8bd5\u4e86\u5728\u5b58\u5728TAK-243\uff08MLN7243\uff09\uff0c\u4e00\u79cd\u5f3a\u6548\u7684\u6cdb\u7d20\u6fc0\u6d3b\u9176\uff08UAE\uff09\u6291\u5236\u5242\u7684\u60c5\u51b5\u4e0b\uff0c\u51dd\u805a\u7269\u7684\u5f62\u6210\u548c\u89e3\u805a\uff08\u56fe2f\uff09\u3002\u4f5c\u8005\u5728\u4e0d\u540c\u65f6\u95f4\u6bb5\u6291\u5236\u6cdb\u7d20\u5316\uff081\uff09\u5728\u9897\u7c92\u5f62\u6210\u548c\u89e3\u805a\u7684\u6574\u4e2a\u5468\u671f\uff08TAK-243-1\uff09\uff0c\uff082\uff09\u5728\u9897\u7c92\u5f62\u6210\u671f\u95f4\uff08TAK-243-2\uff09\uff0c\u4ee5\u53ca\uff083\uff09\u4ec5\u5728\u89e3\u805a\u671f\u95f4\uff08TAK-243-3\uff1b\u56fe2g\uff09\u3002\u8fd9\u4e9b\u6bd4\u8f83\u7ed3\u679c\u663e\u793a\uff0c\u5728\u4efb\u4f55\u4e00\u4e2a\u65f6\u671f\uff08\u7ec41\uff0c2\u62163\uff09\u6291\u5236\u6cdb\u7d20\u5316\u5bf9\u9897\u7c92\u5f62\u6210\u7684\u5f71\u54cd\u8f83\u5c0f\u3002\u7136\u800c\uff0c\u5f53\u5728\u9897\u7c92\u5f62\u6210\u671f\u95f4\u6291\u5236\u6cdb\u7d20\u5316\u65f6\uff08TAK-243-1\u548cTAK-243-2\uff09\u89c2\u5bdf\u5230\u4e86\u663e\u8457\u5ef6\u8fdf\u7684\u9897\u7c92\u89e3\u805a\uff0c\u800c\u5728\u4ec5\u5728\u89e3\u805a\u671f\u95f4\u65bd\u7528TAK-243\u65f6\uff08TAK-243-3\uff09\u5219\u89c2\u5bdf\u5230\u4e86\u8f7b\u5fae\u7684\u5ef6\u8fdf\uff08\u56fe2h\uff09\u3002\u603b\u7684\u6765\u8bf4\uff0c\u8fd9\u4e9b\u7ed3\u679c\u5f3a\u70c8\u8868\u660e\u6cdb\u7d20\u5316\u5bf9\u9897\u7c92\u89e3\u805a\u81f3\u5173\u91cd\u8981\u3002\u00a0 \u00a0<\/section>\n
\"3\"<\/section>\n
\u56fe2 HaloMap\u5206\u6790\u6cdb\u7d20\u5316\u5bf9\u4e8eSG\u89e3\u805a\u662f\u5173\u952e\u7684\u4fee\u9970\u3002<\/section>\n
<\/section>\n
3.\u76f8\u4e92\u4f5c\u7528\u7ec4\u56fe\u8c31 (+\/\u2212)TAK-243 \u786e\u5b9a\u5019\u9009\u8c03\u8282\u56e0\u5b50<\/strong><\/section>\n
\u4f5c\u8005\u56e0\u6b64\u5728HaloTag\u2013G3BP1\u7a33\u5b9a\u7ec6\u80de\u7cfb\u4e0a\u5bf9\u6bd4\u4e86\u6709\u65e0TAK-243\u5904\u7406\u4e0b\u7684\u7ec6\u80de\u5728\u5e94\u6fc0\u524d\u53ca\u6574\u4e2a\u89e3\u805a\u8fc7\u7a0b\u4e2d\u7684\u60c5\u51b5\uff08\u56fe3a\uff09\u3002\u9274\u5b9a\u5230\u7531TAK-243\u6291\u5236\u591a\u805a\u6cdb\u7d20\u5316\u6240\u89e6\u53d1\u7684\u9897\u7c92\u86cb\u767d\u7ec4\u5dee\u5f02\u3002\u4f5c\u8005\u805a\u7126\u4e8e\u4e0e\u6cdb\u7d20\u901a\u8def\u76f8\u5173\u7684\u5dee\u5f02\u5bcc\u96c6\u86cb\u767d\uff0c\u9996\u5148\u641c\u7d22\u4e86E3\u8fde\u63a5\u9176\uff0c\u8bc6\u522b\u51fa\u4e86\u5728\uff08+\uff09TAK-243\u7ec6\u80de\u4e2d\u4e8e\u5e94\u6fc0\u540e\u5bcc\u96c6\u7684\u51e0\u79cd\u5019\u9009\u86cb\u767d\uff08\u56fe3b\u3001c\uff09\u3002\u5176\u4e2d\u5305\u62ecE3\u8fde\u63a5\u9176\uff0c\u8bc6\u522b\u6cdb\u7d20\u7ffb\u8bd1\u540e\u4fee\u9970\uff08PTMs\uff09\u7684\u86cb\u767d\u4ee5\u53ca\u4f5c\u4e3a\u9897\u7c92\u89e3\u805a\u7684\u86cb\u767d\u3002\u4f5c\u8005\u8fd8\u8bc6\u522b\u51fa\u51e0\u79cd\u4e0e\u81ea\u566c\u76f8\u5173\u7684\u6cdb\u7d20\u53d7\u4f53\uff0c\u5305\u62ecSQSTM1\u3001HDAC6\u548cTOLLIP\uff0c\u6240\u6709\u8fd9\u4e9b\u86cb\u767d\u90fd\u5df2\u88ab\u8bc1\u660e\u80fd\u591f\u8bc6\u522b\u805a\u6cdb\u7d20\u5316\u5e95\u7269\u4ee5\u8fdb\u884c\u81ea\u566c\u9776\u5411\u548c\u964d\u89e3\uff08\u56fe3d\u3001e\uff09\u3002<\/section>\n
\"4\"\u56fe3 \u9897\u7c92\u86cb\u767d\u7ec4\u5728\u5e94\u6fc0\u524d\u5230\u665a\u671f\u89e3\u4f53\u72b6\u6001\u4e2d\u7684\u53d8\u5316\uff0c\u5305\u62ec\u6709\uff08+\uff09\u548c\u6ca1\u6709\uff08-\uff09TAK-243\u7684\u60c5\u51b5\u3002<\/section>\n
<\/section>\n
4.HECT E3\u8fde\u63a5\u9176\u4fc3\u8fdb\u9897\u7c92\u89e3\u4f53<\/strong><\/section>\n
\u4f5c\u8005\u5728HaloMap\u5b9e\u9a8c\u4e2d\u53d1\u73b0HECT E3\u8fde\u63a5\u9176\u7684\u5bcc\u96c6\u3002\u4e3a\u4e86\u7814\u7a76HECT E3\u8fde\u63a5\u9176\u662f\u5426\u5728SG\u7684\u89e3\u4f53\u4e2d\u8d77\u4f5c\u7528\uff0c\u4f5c\u8005\u5728\u523a\u6fc0\u548c\u6062\u590d\u671f\u95f4\u7528HECT\u8fde\u63a5\u9176\u7279\u5f02\u6027\u6291\u5236\u5242heclin\u5904\u7406\u7ec6\u80de\u3002\u5728120\u5206\u949f\u7684\u6062\u590d\u671f\uff08D120\uff09\uff0checlin\u5904\u7406\u7684\u6837\u672c\u4e2d\u4ecd\u7136\u6b8b\u7559\u5927\u91cf\u7684\u9897\u7c92\uff08\u56fe4a\uff0cb\uff09\u3002\u4f5c\u8005\u63a5\u4e0b\u6765\u63a2\u7d22\u4e86\u7279\u5b9a\u7684HECT E3\u8fde\u63a5\u9176\u6216\u5176\u76f8\u5173\u7ed3\u5408\u86cb\u767d\u662f\u5426\u8c03\u8282SG\uff08\u5e94\u6fc0\u9897\u7c92\uff09\u7684\u89e3\u4f53\u3002\u4e3a\u6b64\uff0c\u4f5c\u8005\u5bf9\u5728HaloMap\u4e2d\u8bc6\u522b\u7684\u6bcf\u4e2a\u5019\u9009\u86cb\u767d\u8fdb\u884c\u4e86siRNA\u6572\u4f4e\u5b9e\u9a8c\uff0c\u5305\u62ec\u6240\u6709\u56db\u79cd\u8fde\u63a5\u9176\uff08WWP2\u3001ITCH\u3001NEDD4\u548cNEDD4L\uff09\u4ee5\u53ca\u4e24\u4e2a\u7ed3\u5408\u86cb\u767d\uff08NDFIP1\u548cNDFIP2\uff09\u3002\u5355\u72ec\u6572\u4f4eITCH\u3001NEDD4L\u548cNDFIP1\u5bfc\u81f4SG\u89e3\u4f53\u7684\u660e\u663e\u5ef6\u8fdf\u3002\u9274\u4e8e\u8fd9\u4e9b\u8fde\u63a5\u9176\u4e4b\u524d\u672a\u4e0e\u9897\u7c92\u76f8\u5173\u8054\uff0c\u4f5c\u8005\u901a\u8fc7\u9488\u5bf9\u9897\u7c92\u6807\u8bb0\u7269G3BP1\u7684\u514d\u75ab\u8367\u5149\u786e\u8ba4\u4e86\u5b83\u4eec\u7684\u4e9a\u7ec6\u80de\u5b9a\u4f4d\uff0c\u89c2\u5bdf\u5230\u5b83\u4eec\u5728NaAsO2\u5904\u7406\u540e\u88ab\u62db\u52df\u5230SG\u4e2d\uff08\u56fe4e\uff09\u3002\u8fc7\u8868\u8fbe\u6216siRNA\u6572\u4f4eITCH\u6216NEDD4L\u5747\u672a\u5f71\u54cd\u521d\u59cb\u7684\u9897\u7c92\u5f62\u6210\uff0c\u8fd9\u4e0e\u4f5c\u8005\u5bf9TAK-243\u548checlin\u6291\u5236\u591a\u805a\u6cdb\u7d20\u5316\u7684\u7ed3\u679c\u4e00\u81f4\uff08\u56fe4e\uff09\u3002\u7efc\u5408\u8fd9\u4e9b\u6570\u636e\uff0c\u8868\u660e\u7279\u5b9a\u7684HECT E3\u8fde\u63a5\u9176\uff0c\u5305\u62ecITCH\u3001NEDD4L\u53ca\u5176\u76f8\u5173\u7ed3\u5408\u86cb\u767dNDFIP1\uff0c\u76f4\u63a5\u5728\u6cdb\u7d20\u4ecb\u5bfc\u7684SG\u89e3\u4f53\u4e2d\u53d1\u6325\u8c03\u8282\u4f5c\u7528\u3002<\/section>\n
\u4f5c\u8005\u63a5\u4e0b\u6765\u5e0c\u671b\u786e\u5b9aHECT\u4f9d\u8d56\u6027\u6cdb\u7d20\u5316\u5728\u9897\u7c92\u4e2d\u7684\u5177\u4f53\u673a\u5236\u53ca\u5176\u5728\u63a7\u5236\u89e3\u4f53\u901f\u7387\u4e2d\u7684\u4f5c\u7528\u3002\u4f5c\u8005\u6700\u521d\u4f7f\u7528TUBE\u65b9\u6cd5\u5bf9\u5168\u6cdb\u7d20\u5e95\u7269\u53d8\u5316\u5206\u6790\uff0c\u6bd4\u8f83\u5728\u6709\uff08+\uff09\u548c\u65e0\uff08\u2212\uff09heclin\u7684\u60c5\u51b5\u4e0b\u5f62\u6210\u9897\u7c92\u7684\u7ec6\u80de\uff08\u56fe4f\uff09\u3002GO\u5206\u6790\u663e\u793a\u53d7\u5230heclin\u5f71\u54cd\u7684\u6cdb\u7d20\u7ec4\u5728\u56ca\u6ce1\u4ecb\u5bfc\u7684\u8fd0\u8f93\u3001K63\u591a\u805a\u6cdb\u7d20\u94fe\u8c03\u8282\u548c\u81ea\u566c\u65b9\u9762\u8868\u73b0\u51fa\u529f\u80fd\u5bcc\u96c6\u3002\u63a5\u4e0b\u6765\uff0c\u4f5c\u8005\u91cd\u590d\u4e86\u8fd9\u4e2a\u6cdb\u7d20\u7ec4\u5206\u6790\u5b9e\u9a8c\uff0c\u4f46\u4f7f\u7528K63\u7279\u5f02\u6027TUBE\u5bcc\u96c6\uff08\u56fe4f\uff09\u3002\u5728\u6b64\u8fc7\u7a0b\u4e2d\uff0c\u4f5c\u8005\u8bc6\u522b\u5230181\u4e2a\u901a\u5e38\u5728\u5e94\u6fc0\u4e0bK63\u7279\u5f02\u6027\u6cdb\u7d20\u5316\u589e\u52a0\u4f46\u5728heclin\u5904\u7406\u540e\u663e\u8457\u964d\u4f4e\u4fee\u9970\u6c34\u5e73\u7684\u86cb\u767d\uff0c\u5176\u4e2d31\u4e2a\u5df2\u77e5\u662fSG\u6210\u5206\u3002\u514d\u75ab\u8367\u5149\u5206\u6790\u663e\u793aheclin\u5904\u7406\u671f\u95f4\u9897\u7c92\u533a\u57df\u5185K63\u7279\u5f02\u6027\u6cdb\u7d20\u4fe1\u53f7\u7684\u91cd\u53e0\u51cf\u5c11\uff08\u56fe4g\uff09\u3002\u8fd9\u4e9b\u6570\u636e\u8868\u660eHECT E3\u8fde\u63a5\u9176\u901a\u8fc7\u8c03\u63a7\u7279\u5b9a\u9897\u7c92\u86cb\u767d\u4e0a\u7684K63\u591a\u805a\u6cdb\u7d20\u5316\u6765\u8c03\u8282\u9897\u7c92\u7684\u89e3\u4f53\u3002\u00a0 \u00a0<\/section>\n
\"5\"<\/section>\n
\u56fe4 \u00b5Map\u63ed\u793a\u6d3b\u7ec6\u80de\u4e2d\u5e94\u6fc0\u9897\u7c92\u89e3\u4f53\u673a\u5236\u3002<\/section>\n
<\/section>\n
\u540e\u7eed\uff0c\u4f5c\u8005\u9274\u5b9a\u5230\u6cdb\u7d20\u53d7\u4f53TOLLIP\u86cb\u767d\uff0c\u5e76\u901a\u8fc7\u81ea\u566c\u9014\u5f84\u4ecb\u5bfc\u9897\u7c92\u52a8\u6001\u3002<\/section>\n
<\/section>\n
5.\u603b\u7ed3<\/strong><\/section>\n
\u5728\u672c\u7814\u7a76\u4e2d\uff0c\u4f5c\u8005\u5e94\u7528\u57fa\u4e8eHaloTag\u7684\u5e73\u53f0\uff08\u03bcMap\uff09\u8fdb\u884c\u90bb\u8fd1\u6807\u8bb0\uff0c\u4ee5\u8868\u5f81\u6d3b\u7ec6\u80de\u4e2d\u7684\u5e94\u6fc0\u9897\u7c92\u52a8\u6001\u53d8\u5316\u3002\u63ed\u793a\u4e86\u82e5\u5e72\u4e0e\u6cdb\u7d20\u76f8\u5173\u7684\u8c03\u8282\u56e0\u5b50\uff0c\u5305\u62ecHECT\uff08\u4e0eE6AP C\u672b\u7aef\u540c\u6e90\uff09E3\u8fde\u63a5\u9176ITCH\u548cNEDD4L\uff0c\u4ee5\u53ca\u6cdb\u7d20\u53d7\u4f53TOLLIP\uff0c\u4f5c\u4e3a\u9897\u7c92\u89e3\u4f53\u7684\u5173\u952e\u4ecb\u5bfc\u56e0\u5b50\u3002\u6b64\u5916\uff0c\u4f5c\u8005\u8fd8\u8bc6\u522b\u51fa\u4e00\u4e2a\u4fc3\u8fdb\u9897\u7c92\u6e05\u9664\u7684\u81ea\u566c\u76f8\u5173\u901a\u8def\u3002\u603b\u7684\u6765\u8bf4\uff0c\u8fd9\u9879\u5de5\u4f5c\u5efa\u7acb\u4e86\u4e00\u79cd\u5e38\u89c4\u7684\u5149\u50ac\u5316\u7684\u90bb\u8fd1\u6807\u8bb0\u65b9\u6cd5\uff0c\u7528\u4e8e\u63ed\u793a\u7ec6\u80de\u5185\u86cb\u767d\u8d28\u76f8\u4e92\u4f5c\u7528\u7ec4\uff0c\u5e76\u53d1\u73b0\u4e86\u8c03\u8282\u5e94\u6fc0\u9897\u7c92\u52a8\u6001\u7684\u5148\u524d\u672a\u63a2\u8ba8\u7684\u673a\u5236\u3002<\/section>\n
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\u672c\u6587\u4f5c\u8005\uff1aZYS<\/section>\n
\u8d23\u4efb\u7f16\u8f91\uff1aZWY<\/section>\n
\u539f\u6587\u94fe\u63a5\uff1ahttps:\/\/www.nature.com\/articles\/s41589-024-01721-2<\/section>\n
\u539f\u6587\u5f15\u7528\uff1adoi: 10.1038\/s41589-024-01721-2<\/section>\n

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