ngµç×ÓÓÎÏ·

05

¿ÆÑÐÏ£Íû

¶àÖÖÐÂÐÍÂѰ×ÐÞÊζԹÌÓÐÃâÒßÐźÅÍøÂçµÄµ÷¿ØÐ»úÖÆ

¸å¼þȪԴ£º£ºÉúÃü¿ÆÑ§Ñ§Ôº ±à¼­£º£ºÌ¸Ï£¡£¡¢Íõ¶¬Ã· ÉóºË£º£ºÖª×ã ÔĶÁÁ¿£º£º

ngµç×ÓÓÎÏ·ÐÂÎÅÍøÑ¶£¨Í¨Ñ¶Ô±´ÞöÁ£©ÂѰ×ÖÊÊÇ×é³ÉÉúÃüµÄÎïÖÊ»ù´¡£¬£¬ÊÇÉúÃü»î¶¯µÄÖ÷Òª³Ðµ±Õߣ¬£¬È»¶øÂѰ×ÖÊÔںϳÉÖ®ºó£¬£¬ÍùÍùÐèÒª¾­ÓÉһϵÁÐÂѰ×ÖÊ·­ÒëºóÐÞÊÎ(Protein post-translational modifications, PTMs)£¬£¬Í¨¹ý¹¦Ð§»ùÍŵÄÌí¼Ó»òÈ¥³ý£¬£¬µ÷ÀíÂѰ×ÖʵÄÉú»¯ÐÔ×Ó´Ó¶ø¸Ä±äÆä»îÐÔ¡£¡£¡£¿ËÈÕ£¬£¬ngµç×ÓÓÎÏ·ÉúÃü¿ÆÑ§Ñ§Ôº´ÞöÁ¿ÎÌâ×éÔÚMolecular CellÔÓÖ¾83ÆÚÉÏÁ¬Ðø½ÒÏþÁ½ÆªÑ§ÊõÂÛÎÄ£¬£¬»®·ÖÕ¹ÏÖÁËÂѰ×רéµõ£»£»£»¯ºÍ½¹Á×ËữÕâÁ½ÖÖÐÂÐÍPTM¶Ô¹ÌÓÐÃâÒßÓ¦´ðµÄÒªº¦µ÷¿Ø×÷ÓûúÖÆ¡£¡£¡£

ÂѰ×רéµõ£»£»£»¯½éµ¼×ÔÊɺÍNLRP3Ñ×֢СÌ廥×÷µ÷¿ØÑ×Ö¢¼°ÆäÏà¹Ø¼²²¡µÄлúÖÆ

NLRP3Ñ×֢СÌåÊǹÌÓÐÃâÒßϵͳµÄÖ÷Òª×é³É²¿·Ö£¬£¬Æä¹¦Ð§ÔÓÂÒÓë×ÔÉíÑ×Ö¢ÐÔ¼²²¡¡¢Éñ¾­ÐÔÍËÐÐÐÔ¼²²¡ÒÔ¼°°©Ö¢µÄ±¬·¢¿ªÕ¹Ç×½üÏà¹Ø¡£¡£¡£NLRP3Í»±äÒýÆðÑ×֢СÌåµÄÌ«¹ý¼¤»îÊÇÔç·¢ÐÍÑ×Ö¢ÐÔ³¦²¡£¡£¡£¨VEOBD£©¡¢Ó×ÄêÌØ·¢ÐÔÊàŦÑ×£¨JIA£©ºÍÀäßÁßøÏà¹ØÖÜÆÚÐÔ×ÛºÏÕ÷£¨CAPS£©µÈ×ÔÉíÑ×Ö¢¼²²¡µÄÖ÷ҪΣÏÕÒòËØ£¬£¬Òò´ËÆä»î»¯±ØÐ豻ϸÄåµ÷¿ØÒÔά³ÖÃâÒßÎÈ̬¡£¡£¡£´ÞöÁ¿ÎÌâ×é·¢Ã÷S-רéµõ£»£»£»¯Í¨¹ý½éµ¼·Ö×ÓÅóÙ­½éµ¼µÄ×ÔÊÉ£¬£¬ÔÚµ÷¿ØNLRP3ÂѰ×ÎȹÌÐÔÖÐʩչÖ÷Òª¹¦Ð§£¬£¬²¢Õ¹ÏÖS-רéµõ£»£»£»¯È±ÏݵÄNLRP3Í»±äÓë×ÔÉíÑ×Ö¢ÐÔ¼²²¡µÄ±¬·¢¾ßÓÐÒ»¶¨µÄÏà¹ØÐÔ¡£¡£¡£

S-רéµõ£»£»£»¯ÊÇÒ»ÖÖÐÂÐ͵ÄÂѰ׷­ÒëºóÐÞÊΣ¬£¬¼ÓÈëÐí¶àÃâÒßÏà¹ØÂѰ×ÖʵÄתÔË¡¢¶¨Î»ºÍÎȹÌÐԵĵ÷Àí¡£¡£¡£È»¶ø£¬£¬S-רéµõ£»£»£»¯ÊÇ·ñÔÚµ÷¿ØNLRP3Ñ×֢СÌ弤»îÀú³ÌÖÐʩչҪº¦×÷ÓÃÉÐÓдýÆÊÎö¡£¡£¡£¸ÃÑо¿Á¬ÏµS-רéµõ£»£»£»¯ÒÖÖÆ¼Á2-bromopalmitate£¨2BP£©´¦Àí¡¢õ£»£»£»ù-ÉúÎïËØ½»Á÷¡¢S-רéµõ£»£»£»¯ÐÞÊ樵ãÍ»±ä¡¢ÂѰ׻¥×÷ÖÊÆ×¡¢¹ý±í´ï/Çóýרéµõ£×ªÒÆÃ¸ZDHHC12µÈʵÑ飬£¬Ö¤ÊµZDHHC12¿ÉÒÔÏÔ×ÅÔö½øNLRP3µÄרéµõ£»£»£»¯ÐÞÊΣ¬£¬¶øÆäø»îȱʧͻ±äZDHHC12 C127SÔò²»¿É£¬£¬Åú×¢ZDHHC12Ôö½øNLRP3µÄרéµõ£»£»£»¯ÐÞÊÎÒÀÀµÓÚÆäø»îÐÔ¡£¡£¡£½øÒ»²½µÄÑо¿·¢Ã÷Zdhhc12ȱÏÝ¿ÉÔÚСÊóÌåÄÚÔö½øNLRP3Ñ×֢СÌåµÄ¼¤»îºÍIL-1¦ÂµÄÊÍ·Å£¬£¬´Ó¶ø¼ÓÖØAlumÓÕµ¼µÄ¸¹Ä¤Ñ×ÒÔ¼°LPSÓÕµ¼µÄŧ¶¾ÑªÖ¢£¬£¬Õ¹ÏÖZDHHC12ÔÚ»úÌåÖÐʩչ·ÀÖ¹NLRP3Ñ×֢СÌåÌ«¹ý¼¤»îµÄÖ÷Òª×÷Óᣡ£¡£Í¨¹ýÒÖÖÆ¼ÁʵÑ飬£¬Ñо¿Ö°Ô±·¢Ã÷ÈÜøÌåÒÖÖÆ¼ÁNH4ClºÍCQÄܹ»ÏÔÖøÒÖÖÆZDHHC12¶ÔNLRP3µÄ½µ½â×÷Óᣡ£¡£½øÒ»²½Ñо¿·¢Ã÷ZDHHC12½éµ¼µÄS-רéµõ£»£»£»¯ÐÞÊÎͨ¹ýÔöÇ¿NLRP3Óë·Ö×ÓÅóÙ­HSC70µÄÁ¬Ïµ£¬£¬Ôö½øNLRP3½øÈëÈÜøÌå¾ÙÐнµ½â£¬£¬×îÖÕÒÖÖÆNLRP3Ñ×֢СÌåµÄ¼¤»î¡£¡£¡£

ΪÁË̽ÌÖ×ÔÉíÑ×Ö¢ÐÔ¼²²¡Ïà¹ØµÄNLRP3Í»±äÊÇ·ñÓëרéµõ£»£»£»¯Ê§µ÷Ïà¹Ø£¬£¬Ñо¿Ö°Ô±É¸Ñ¡ÁËһϵÁÐNLRP3Í»±ä²¢·¢Ã÷ NLRP3µÄD21H¡¢S102L¡¢R490K¡¢ºÍG571RÍ»±ä¿ÉÒÔͨ¹ýÒÖÖÆNLRP3µÄS-רéµõ£»£»£»¯ÐÞÊÎÒÔÔöÇ¿ÆäÎȹÌÐÔ£¬£¬´Ó¶øÔö½øÑ×Ö¢·´Ó³¡£¡£¡£½øÒ»²½µÄ»úÖÆÑо¿Åú×¢£¬£¬ÕâÊÇÓÉÓÚNLRP3µÄÏìӦͻ±ä½µµÍÁËNLRP3ÓëZDHHC12µÄÁ¬Ïµ£¬£¬´Ó¶øÒÖÖÆHSC70¶ÔNLRP3µÄʶ±ðºÍ½µ½â¡£¡£¡£ÓÉÓÚNLRP3 µÄS102LÍ»±äÔÚÑÇÖÞÈËȺÖÐÆµÂʽϸߣ¬£¬ÇÒÔÚJIAºÍCAPSµÈ×ÔÉíÑ×Ö¢ÐÔ¼²²¡»¼ÕßÌåÄÚ±»¶à´Î·¢Ã÷£¬£¬¸ÃÑо¿½«ÓÐÖúÓÚ NLRP3Í»±äÏà¹ØµÄ×ÔÉíÑ×Ö¢ÐÔ¼²²¡»¼ÕßµÄÕï¶ÏÓë׼ȷÖÎÁÆ¡£¡£¡£¼øÓÚS-רéµõ£»£»£»¯ÐÞÊζÔNLRP3ÂѰ׼¤»îºÍÎȹÌÐÔµÄÖ÷Òªµ÷¿Ø×÷Ó㬣¬ÌØÒì°ÐÏòרéµõ£×ªÒÆÃ¸µÄÒ©Îï¿ÉÄÜÊÇÖÎÁÆ×ÔÉíÑ×Ö¢ÐÔ¼²²¡µÄÀíÏë°Ð±ê¡£¡£¡£


3B2B7F7DD903C9981725AE202DB_9064CC9A_155E9

ͼ1 ZDHHC12ͨ¹ýרéµõ£»£»£»¯£¬£¬ÓÕµ¼NLRP3̫ͨ¹ý×ÓÅóÙ­½éµ¼µÄ×ÔÊɽµ½â£¬£¬ÒÖÖÆÌ«¹ýÑ×Ö¢·´Ó³µÄÊÂÇéÄ£×Ó


ÕâÆªÑо¿ÂÛÎĵĵÚÒ»×÷ÕßÊÇngµç×ÓÓÎÏ·ÉúÃü¿ÆÑ§Ñ§ÔºÍõÀöÇñ²©Ê¿£¬£¬ËýµÄÖ÷ÒªÑо¿Æ«ÏòΪÑ×֢СÌåµÄÃâÒßµ÷¿Ø»úÖÆ£¬£¬ÓÚ2022ÄêÈëÑ¡²©Ê¿ºóÁ¢ÒìÈ˲ÅÖ§³ÖÍýÏ룬£¬²¢ÔÚNature Communications¡¢Cellular & Molecular ImmunologyµÈÔÓÖ¾½ÒÏþ¶àƪһ×÷ÎÄÕ¡£¡£¡£´ÞöÁ½ÌÊÚΪ¸ÃÂÛÎĵÄͨѶ×÷Õß¡£¡£¡£¸ÃÑо¿»ñµÃ¹ú¼Ò×ÔÈ»¿ÆÑ§»ù½ðºÍ²©Ê¿ºóÁ¢ÒìÈ˲ÅÖ§³ÖÍýÏëµÈ¾­·ÑÖ§³Ö¡£¡£¡£

ÂѰ׽¹Á×Ëữµ÷¿Ø¿¹²¡¶¾¹ÌÓÐÃâÒßµÄлúÖÆ

Á×ËữÐÞÊÎÊÇÏÖÔÚÒÑÖªÂþÑÜ×îΪÆÕ±éµÄPTM¡£¡£¡£ÂѰ×ÖÊÁ×ËữµÄÏà¹ØÑо¿Æð²½ÓÚ20ÊÀ¼Í³õ£¬£¬Ö±µ½½üÊ®Ä꣬£¬Ã¿ÄêÆ½¾ùÈÔÓÐ1.5ÍòƪÏà¹ØÑо¿±»±¨µÀ¡£¡£¡£¾ÝÔ¤¼Æ£¬£¬ÕæºËÉúÎïÖÐÓпìÒª1/3µÄÂѰ×Äܹ»±»Á×Ëữ¡£¡£¡£ÈËÀàÂѰ×ÖÊ×éÖк¬ÓÐ10¶àÍò¸öDZÔÚµÄÁ×Ëữλµã¡£¡£¡£Ïà¹ØÓÚÁ×ËữÐÞÊΣ¬£¬ÂѰ׵Ľ¹Á×ËữÐÞÊÎ×÷ΪһÖÖз¢Ã÷µÄPTM£¬£¬Ñо¿ÀúÊ·Ïà¶Ô½Ï¶Ì¡£¡£¡£½¹Á×ËữÐÞÊÎ×îÔç±»·¢Ã÷ÓÚÌÇÔ­ºÏ³ÉÖС£¡£¡£ÓÉÓÚÏÖÔÚûÓÐÂѰ×ÖʵĽ¹Á×ËữøµÄÏà¹Ø±¨µÀ£¬£¬Ò»°ãÒÔΪÂѰ׽¹Á×ËữÊôÓÚÎÞø´ß»¯µÄÐÞÊΡ£¡£¡£´ÞöÁ¿ÎÌâ×é·¢Ã÷½¹Á×ËữøUAP1¿ÉÒÔÁ¬Ïµµ½×ªÂ¼Òò×ÓIRF3ÉÏ£¬£¬Ö±½ÓÕýÏòµ÷¿ØIÐÍ×ÌÈÅËØ·´Ó³£¬£¬»¹·¢Ã÷UAP1×÷ΪµÚÒ»¸ö±»·¢Ã÷µÄÂѰ׽¹Á×Ëữø£¬£¬Í¨¹ý´ß»¯IRF3µÄ½¹Á×Ëữ£¬£¬ÔöÇ¿»úÌå¹ÌÓÐÃâÒßÓ¦´ð£¬£¬½µµÍ²¡¶¾Ñ¬È¾µÄлúÖÆ¡£¡£¡£

¸ÃÑо¿Ê×ÏÈͨ¹ý¹¦Ð§É¸Ñ¡£¬£¬·¢Ã÷ÇóýÌÇ»ù»¯µ×ÎïºÏ³ÉÖÐÒªº¦µÄ½¹Á×ËữøUAP1Äܹ»ÏÔ×ÅÒÖÖÆÏ¸°ûµÄ¿¹²¡¶¾»îÐÔ£¬£¬¶ø¹ý±í´ïUAP1Ôò»áÔöÇ¿IÐÍ×ÌÈÅËØÒÔ¼°×ÌÈÅËØ´Ì¼¤»ùÒòµÄ±í´ï¡£¡£¡£Uap1Çõ͵ÄСÊó¶ÔÖݪֲ¡¶¾µÄѬȾ¶¼¸üÃô¸Ð£¬£¬Æä¿¹²¡¶¾ÄÜÁ¦ÏÔ×ÅϽµ£¬£¬Õ¹ÏÖÁËÆäÔÚ»úÌ忹²¡¶¾ÃâÒßÖеÄÖ÷Òª×÷Óᣡ£¡£ÎªÁË̽ÌÖUAP1µ÷¿Ø¿¹²¡¶¾ÃâÒßµÄÏêϸ»úÖÆ£¬£¬Ñо¿Ö°Ô±Í¨¹ýÃâÒß¹²³ÁµíʵÑé·¢Ã÷UAP1¿ÉÒÔÌØÒìÐÔÁ¬Ïµ×ªÂ¼Òò×ÓIRF3¡£¡£¡£UAP1µÄø»îÍ»±äÌåËðʧÁËÆäÔö½øIÐÍ×ÌÈÅËØÍ¨Â·¼¤»îµÄÄÜÁ¦£¬£¬Åú×¢UAP1µÄ¿¹²¡¶¾¹¦Ð§ÒÀÀµÓÚÆäø»îÐÔ¡£¡£¡£Ñо¿Ö°Ô±½øÒ»²½È·¶¨UAP1Ö÷Ҫͨ¹ý´ß»¯IRF3µÄ½¹Á×ËữÐÞÊΣ¬£¬¶ø²»ÊÇÌÇ»ù»¯ÐÞÊÎÓ°ÏìIRF3µÄ»îÐÔ¡£¡£¡£Í¨¹ýÒÖÖÆ¼ÁʵÑ飬£¬Ñо¿Ö°Ô±·¢Ã÷O-ÌÇ»ù»¯ÒÖÖÆ¼Á£¨OSMI-1£©»òÕßN-ÌÇ»ù»¯ÒÖÖÆ¼Á£¨TM£©´¦Àíϸ°û²»»áÓ°ÏìUAP1¶ÔIÐÍ×ÌÈÅËØµÄÔö½ø×÷Ó㬣¬¶ø½¹Á×ËữÐÞÊÎÒÖÖÆ¼Á£¨TNP£©´¦Àí»áÏÔ×ÅÒÖÖÆUAP1µÄ¿¹²¡¶¾¹¦Ð§¡£¡£¡£²¹»ØUAP1ÔÚ¼ºÌǰ·Í¨Â·ÖеÄÖ÷Òª²úÆ·UDP-N-ÒÒõ£»£»£»ùÆÏÌÑÌǰ·£¬£¬²»¿É»Ø¸´ÇóýUAP1¶ÔIRF3¼°Æä¿¹²¡¶¾ÃâÒߵĵ÷¿Ø×÷Ó㬣¬Õ¹ÏÖÁËUAP1¿ÉÄÜÖ±½Óͨ¹ý´ß»¯ÂѰ׵Ľ¹Á×Ëữʩչ¹¦Ð§¡£¡£¡£½øÒ»²½µÄÑо¿Í¨¹ýÍ¬Î»ËØÊ¾×Ù·¨¡¢½¹Á×ËáÊÔ¼ÁºÐ¼ì²âÒÔ¼°ÖÊÆ×ʵÑéµÈ²î±ðʵÑéÒªÁ죬£¬Ö¤ÊµUAP1Äܹ»ÌØÒìÐÔ´ß»¯IRF3µÄSer386λµãµÄ½¹Á×ËữÐÞÊΡ£¡£¡£Ñо¿Ö°Ô±¹¹½¨ÁËSer386λµãʧ»îµÄS386AÍ»±äÌ壬£¬·¢Ã÷S386µãÍ»±äºóIRF3²»¿É½øÒ»²½»î»¯£¬£¬IRF3 C¶Ë5ST»îÐÔλµã£¨Ser396£©Ò²²»¿É±¬·¢Á×Ëữ£¬£¬Í¬Ê±IRF3¶þ¾Û»¯ºÍÈëºËÄÜÁ¦Ò²ÏÔ×ÅϽµ£¬£¬ÕâЩЧ¹ûÅú×¢UAP1½éµ¼µÄ½¹Á×ËữÐÞÊη´¿¹²¡¶¾¹ÌÓÐÃâÒߵĵ÷¿ØÖÁ¹ØÖ÷Òª¡£¡£¡£


22BEB933C79740B124735EC13BD_776487D5_D307

ͼ2 UAP1ͨ¹ý´ß»¯IRF3½¹Á×Ëữ£¬£¬µ÷¿ØIRF3»îÐÔ¼°ÆäIÐÍ×ÌÈÅËØÐźÅͨ·µÄÊÂÇéÄ£×Ó


ngµç×ÓÓÎÏ·ÉúÃü¿ÆÑ§Ñ§Ôº´ÞöÁ½ÌÊÚΪ¸ÃÑо¿ÂÛÎĵÄͨѶ×÷Õߣ¬£¬ngµç×ÓÓÎÏ·ÉúÃü¿ÆÑ§Ñ§ÔºÑî˧²©Ê¿ÎªµÚÒ»×÷Õß¡£¡£¡£¸ÃÑо¿»ñµÃÁ˹ú¼Ò×ÔÈ»¿ÆÑ§»ù½ðµÈ¾­·ÑÖ§³Ö¡£¡£¡£

ÂÛÎÄÁ´½Ó£º£º1. https://doi.org/10.1016/j.molcel.2022.12.002

      2. https://doi.org/10.1016/j.molcel.2022.12.007

¡¾ÍøÕ¾µØÍ¼¡¿