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DDX3µÄµ÷¿ØÒòËؼ°ÉúÎïѧ¹¦ÓÃ

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·¢²¼ÓÚ£º2021-02-22 ¹²15436×Ö

¡¡¡¡Õª    Òª£º¡¡DEAD-box RNA½âÐýø3(DEAD-box RNA helicase 3,DDX3),Òà³ÆDEAD-box RNA½âÐýø3 XÁ¬Ëø(DEAD-box RNA helicase 3 X-linked,DDX3X),ÊÇÒ»Öָ߶ȱ£Êز¢ÒÀÀµATPµÄRNA½âÐýø,¹ã·º·Ö²¼ÓÚÕæºËÉúÎïÖÐ,Ö÷Òª¶¨Î»ÔÚϸ°ûºËºÍϸ°ûÖÊ·¢»ÓÉúÀí×÷ÓÃ,ÓëRNA¼ô½ÓºÍË¥±ä¡¢mRNAÊä³ö¡¢×ªÂ¼¡¢·­ÒëÏà¹Ø,½øÒ»²½²ÎÓëϸ°ûÖÜÆڵĽøÕ¹¡¢ÏÈÌìÃâÒß·´Ó¦¡¢Ï¸°ûµòÍö¡¢°©Ö¢·¢ÉúÓëÒÖÖÆ¡¢²¡¶¾µÄ¸´ÖÆÖÜÆڵȶàÖÖÖØÒªµÄϸ°ûÉúÀí¹ý³Ì.³¤ÆÚÒÔÀ´,DDX3µÄ»ùÒò±í´ï,µ÷¿Ø¼°Æ书ÄÜÒÔ¼°ËüÓë¼²²¡µÄ¹Øϵһֱ±»¹Ø×¢,ÓÈÆäÊÇÓ벡¶¾ºÍ°©Ö¢µÄ¹Øϵ¸üΪÈȵãÑо¿.Òò´Ë,±¾ÎÄÖ÷Ҫ̽ÌÖ¡¢×ܽáDDX3µÄ²¡ÀíÉúÀíѧ×÷ÓÃ.

¡¡¡¡¹Ø¼ü´Ê£º¡¡DEAD-box RNA½âÐýø3; DEAD-box RNA½âÐýø3 XÁ¬Ëø; RNA; Ö×Áö; ²¡¶¾;

¡¡¡¡Abstract£º¡¡DEAD-box RNA helicase 3(DDX3), also known as DEAD-box RNA helicase 3 X-linked(DDX3 X), is a highly conserved ATP-dependent RNA helicase. It widely distributes in eukaryotes, and mainly locates in the nucleus and cytoplasm to play physiological roles. It is related to RNA splicing and decay, mRNA output, transcription and translation, thus regulating cell cycle progression, innate immune response, apoptosis, cancer development and inhibition, virus replication cycle and many other important cellular physiological processes. For a long time, the gene expression, regulation and function of DDX3 and its relationship with diseases have been paid close attention to, especially the relationship with viruses and cancer has been the focus of many studies. Therefore, this article mainly reviews the pathophysiological effects of DDX3.

¡¡¡¡Keyword£º¡¡DEAD-box RNA helicase 3; DEAD-box RNA helicase 3 X-linked; RNA; tumor; virus;

¡¡¡¡DEAD-boxµ°°×ÖʼÒ×åÁ¥ÊôÓÚ½âÐýø³¬¼Ò×å¢ò,ÊÇ×î´óµÄ½âÐýø¼Ò×å,ÒòÆä½á¹¹ÌØÕ÷»ùÐòAsp(D)-Glu(E)-Ala(A)-Asp(D)¶øµÃÃû[1,2].DEAD-boxµ°°×¾ßÓжÀÌصÄ12¸ö±£ÊØ»ùÐò,ÊÇÆä½áºÏ¡¢Ë®½âATPÒÔ¼°ÓëRNAÏ໥×÷ÓõĽṹ»ù´¡[3].DEAD-box RNA½âÐýø3(DEAD-box RNA helicase 3,DDX3)ÊÇDEAD-boxµ°°×¼Ò×åµÄÖØÒª³ÉÔ±,¾ßÓÐDEAD-box RNA½âÐýø3 YÁ¬Ëø(DEAD-box RNA helicase 3 Y-linked,DDX3Y)ºÍDEAD-box RNA½âÐýø3 XÁ¬Ëø(DEAD-box RNA helicase 3 X-linked,DDX3X)Á½¸öͬԴÎï, ÍùÍùÒ²½«DDX3ÒýΪDDX3X.DDX3Y»ùÒòλÓÚYȾɫÌåÉÏ,½ö±í´ïÐÛÐÔÉúֳϵͳ[4,5];¶øDDX3X»ùÒòλÓÚXȾɫÌåÉÏ,¹ã·º±í´ïÓÚÈ«Éí¸÷×éÖ¯,²¢²ÎÓëϸ°ûÖÜÆÚ½øÕ¹¡¢ÏÈÌìÃâÒß·´Ó¦¡¢Ï¸°ûµòÍö¡¢°©Ö¢·¢ÉúÓëÒÖÖÆ¡¢²¡¶¾µÄ¸´ÖÆÖÜÆڵȶàÖÖÖØÒªµÄϸ°ûÉúÀí¹ý³Ì,Òò¶øÊܵ½ÁËÈËÃǵĹ㷺Ñо¿[6,7,8,9].±¾Ñо¿Ö¼ÔÚϵͳ×ܽáDDX3µÄ²¡ÀíÉúÀíѧ×÷ÓÃ,×ÅÖØÆäÓë¼²²¡µÄ¹Øϵ¼°ÉúÎïѧ×÷ÓÃ,ÒÔÆÚ̽Ã÷¿ÉÄܵÄÑо¿·½Ïò.
 

DDX3µÄµ÷¿ØÒòËؼ°ÉúÎïѧ¹¦ÓÃ
 

¡¡¡¡1¡¢ DDX3¼ò½é

¡¡¡¡DDX3×÷ΪһÖֽṹ¸ß¶È±£Êز¢ÒÀÀµATPµÄRNA½âÐýø,¹ã·º´æÔÚÓÚ¸÷ÀàÕæºËÉúÎïÖÐ.1997ÄêÑо¿ÈËÔ±Ê״η¢ÏÖÁËÈËÔ´DDX3µ°°×,²¢Í¨¹ýԭλÔÓ½»¼¼Êõ½«Æä»ùÒò¾«È·¶¨Î»ÓÚXp11.3-p11.23λµã[10].ÈËÔ´DDX3±àÂë»ùÒò³¤Ô¼16KB,¹²°üº¬16¸öÄÚº¬×Ó¼°17¸öÍâÏÔ×Ó,±àÂë5.3KBת¼±¾,¶ÔÓ¦662¸ö°±»ùËáµÄ¶àëÄ,¸»º¬Ë¿°±Ëá(11.3%)ºÍ¸Ê°±Ëá(11.4 %)[4,11].ÓëËùÓеÄDEAD-box RNA½âÐýøÏàËÆ,DDX3µÄ½âÐýøºËÐÄÓÉÁ½¸öÀàËÆRecAÑù½á¹¹Óò¹¹³É,ÆäÖаüº¬13¸öÌØÕ÷ÐÔ½âÐýøÐòÁлùÐò,²¢°üÀ¨Í¬Òå»ùÐò¢ò,¸Ã»ùÐòÒÔµ¥¸ö×Öĸ´úÂë¶ÁȡΪD-E-A-D[12,13]. DDX3½âÐýøºËÐĵÄÁ½²à·Ö±ðÊÇÒ»¸öÐòÁи´ÔӶȵÍÇÒ¾ßÓÐRSÑù½á¹¹ÓòµÄCÄ©¶ËºÍÒ»¸ö´øÓкËÊä³öÐźÅ(nuclear export signal,NES)ÇÒÐòÁи´ÔӶȵ͵ÄNÄ©¶Ë[12,14].Ñо¿ÈËԱͨ¹ýµ°°×Öʽᾧ¼¼ÊõºÍXÉäÏßÑÜÉä·ÖÎö,׼ȷµÃµ½ÁËDDX3½âÐýø½á¹¹ÓòµÄ¾§Ìå½á¹¹,¸Ã¾§ÌåÊôÓÚµ¥Ð±¿Õ¼äȺP21,Æä¾ßÌ徧°û²ÎÊý:a=43.85 ?, b=60.72 ?,c=88.39 ?,α=γ=90°,β=101.02°,²¢·¢ÏÖDDX3½á¾§ÖдæÔÚ¹²½á¾§ÅäÌå,½øÒ»²½Ñо¿·¢ÏÖ¸ÃÅäÌåÄÜÌá¸ßDDX3µÄÈÈÎȶ¨ÐÔ[15,16].DDX3×÷ΪһÖÖ´©Ë󵰰׶¨Î»ÓÚϸ°ûºËºÍϸ°ûÖÊ,²¢ÔÚÆäÖз¢»ÓÏàÓ¦µÄ²¡ÀíÉúÀíѧ¹¦ÄÜ,¼ÈÍùÑо¿·¢ÏÖDDX3δÐÞÊε¥ÌåÐÎʽ(Ïà¶Ô·Ö×ÓÁ¿Îª73.2)¹ý´ó,ÎÞ·¨ÓÐЧͨ¹ýºË¿×±»¶¯À©É¢½øÈëϸ°ûÖÊ,ÐèÒªNÄ©¶Ë¸»º¬ÁÁ°±ËáµÄNESÓëºË³ö¿ÚÊÜÌåϸ°ûȾɫÌåά³Öµ°°×1 (chromosomal region maintenance 1, CRM1,Ò²³ÆExportin-1)½áºÏ,´Ó¶ø¶¨Î»ÖÁºËĤ¿×µÄϸ°ûÖʲà[17,18].×î½ü·¢ÏÖ,DDX3µÄºËÊä³ö²»½öÓÉCRM1½éµ¼,»¹ÒÀÀµÓÚNESºÍÒԻGTP½áºÏÐÎʽÔËÐеĵ¥ÌåÄñàÑßʺËÜÕËá½áºÏµ°°×Ran[17].

¡¡¡¡2¡¢ DDX3µÄµ÷¿ØÒòËØ

¡¡¡¡Ðí¶àÒòËØ»áÔì³ÉDDX3»ùÒòÍ»±äÖÂʹÆ书Äܵĸıä,Ñо¿ÈËԱͨ¹ýÍâÏÔ×Ó×é²âÐòÔÚËèĸϸ°ûÁö¡¢Í·¾±²¿ÁÛ״ϸ°û°©ºÍѪҺϵͳ¶ñÐÔÖ×ÁöÖоù·¢ÏÖÁËDDX3Í»±ä,DDX3µÄÍ»±ä±»ÈÏΪÊǵ¼ÖÂÖ×Áö·¢ÉúµÄÖØÒªÒòËØ[19,20,21].DDX3µÄת¼ͬÑùÊܵ½¶àÖÖÒòËصĵ÷½Ú,ÔÚÈËÈéÍ·Áö²¡¶¾Ïà¹ØµÄ·Î°©ÖÐ,p53 ¶ÔDDX3µÄת¼·¢»Óµ÷¿Ø×÷ÓÃ,p53µÄ״̬¾ö¶¨ÁËDDX3µÄ±í´ïˮƽ[22,23];ÔÚÈéÏÙ°©°éȱÑõÌõ¼þÏÂ,µÍÑõÓÕµ¼Òò×Ó1α(hypoxia-inducible factor-1α,HIF-1α)ͨ¹ýÓëÕý³£ÈéÏÙÉÏƤMCF10Aϸ°ûÖÐDDX3Æô¶¯×ÓÇøµÄµÍÑõÓÕµ¼Òò×ÓÓ¦´ðÔª¼þÏà½áºÏ,´Ó¶øÓÕµ¼¼¤»îDDX3µÄת¼,Òò´ËºËDDX3Ò²±»ÈÏΪÊÇÈéÏÙ°©²»Á¼Ô¤ºóµÄÔ¤²âÒò×ÓÖ®Ò»[24,25].±ûÐ͸ÎÑײ¡¶¾(hepatitis C virus,HCV)µÄ½á¹¹ºËÐĵ°°×±»ÈÏΪÊǵÚÒ»¸ö¿ÉÒÔÓëÈËÀàDDX3Ï໥×÷ÓõIJ¡¶¾µ°°×,Ïà¹Ø¹¦ÄÜʵÑé±íÃ÷,HCVºËÐĵ°°×Ò²ÐíÄܹ»ÔöÇ¿DDX3ת¼¹²¼¤»î×ӵŦÄÜ[11].ÔÚ·­Òëˮƽ,¼¤»îת¼Òò×ÓE74 ÑùÒò×Ó3(E74-like factor 3,elF3)ºÍCapÒÀÀµÐÔ·­Òë»òÒÖÖÆE74 ÑùÒò×Ó4(E74-like factor 4,elF4)¾ùµ÷¿ØDDX3µÄ·­Òë[26,27].ÁíÍâDDX3µÄ±í´ï»¹ÊÜ1ÐÍ°¬×̲¡²¡¶¾(human immunodeficiency virus type 1, HIV-1)Tat(HIV-1±àÂëµÄ·´Ê½¼¤»îÒò×Ó)´Ì¼¤[28];Ôڸΰ©ÖÐ,Ó¦Óÿ¨ÂíÀ­ËØ(rottlerin)¿ÉÉϵ÷DDX3ÔÚÖ×Áöϸ°ûÖеıí´ï[29].´ËÍâ,Éú»îÏ°¹ßÒ²ÃÜÇÐÓ°Ïì×ÅDDX3µÄ±í´ï,°üÀ¨ÎüÑÌ¡¢Òû¾Æ¼°ÆäËûÏ°¹ß,ÇÒÄÐÐÔ±í´ïˮƽ¸ßÓÚÅ®ÐÔ[30].

¡¡¡¡3¡¢ DDX3Óë¼²²¡µÄ¹Øϵ

¡¡¡¡DDX3¶ÔÏÂÓÎÖÚ¶à·Ö×Ó¾ßÓе÷¿Ø×÷ÓÃ,²ÎÓëÁËÏÈÌìÃâÒß·´Ó¦¡¢Ö×ÁöµÄ·¢ÉúÓëÒÖÖÆ¡¢²¡¶¾µÄÖÜÆÚ¸´ÖƵȶàÖÖÉúÎïѧ¹ý³Ì,²¢ÔÚÆäÖз¢»ÓÁËÖØÒªµÄ²¡ÀíÉúÀíѧ×÷ÓÃ[7,9,31].³¤ÆÚÒÔÀ´,DDX3Óë¼²²¡µÄ¹Øϵ±»²»¶Ï̽Ë÷,ÆäÓëÖ×ÁöµÄÑо¿³É¹û·á¸»,Ó벡¶¾Ö®¼äÒ²ÓÐÃ÷È·µÄÁªÏµ.

¡¡¡¡3.1 ¡¢DDX3ÓëÖ×ÁöµÄ¹Øϵ

¡¡¡¡DDX3¿É³äµ±ÀÒµ°°×¼¤Ã¸1ε(casein kinase 1ε, CK1ε)µÄµ÷½ÚÑÇ»ù,Ö±½Ó½áºÏCK1ε²¢´Ì¼¤¼¤Ã¸»îÐÔ,½øÒ»²½´ÙÉ¢ÂÒµ°°× (disheveled protein,Dvl)Á×Ëữ,´Ó¶øʹβ-Á¬»·µ°°×(β-catenin)ÒÆλ½øÈëϸ°ûºË²¢´¥·¢Wnt/β-cateninÐźŴ«µ¼,Wnt/β-cateninÐźÅÏÂÓÎÓÐÖÚ¶à°Ð»ùÒò±»µ÷¿Ø,Ö÷Òª°üÀ¨×ªÂ¼Òò×ÓSnail1¡¢»ùÖʽðÊôµ°°×ø7(matrix metalloproteinase 7,MMP7)¡¢ÊóÀàÈâÁö²¡¶¾°©»ùÒò(kirsten rat sarcoma viral oncogene, KRAS)¡¢³ÉÏËάϸ°ûÌØÒìµ°°×1(fibroblast-fpecific protein 1,FSP1)ºÍÏËÁ¬µ°°×µÈ,ÕâЩ°Ðµã»ùÒò´ó¶à²ÎÓëÉÏƤ¼äÖÊת»¯(epithelial-mesenchymal transformation,EMT)¡¢ÇÖÏ®¡¢Ñ×Ö¢¡¢Ç¨ÒÆ¡¢µòÍöºÍÏËά»¯µÈ¹ý³Ì[32,33,34,35,36,37,38].Wnt/β-cateninºÍEMTÊÇDDX3ÔÚÖ×Áö·¢Éú·¢Õ¹¹ý³ÌÖз¢»ÓÖ°©»òÒÖ°©Ë«ÖØ×÷ÓõĹؼü.

¡¡¡¡ÔÚKRASÍ»±äµÄ½áÖ±³¦°©Ï¸°ûÖÐ,ÖÊÁ£¹¹½¨ÓëתȾ½á¹û±íÃ÷DDX3¿Éͨ¹ýCK1ε/Dvl2Öἤ»îβ-catenin/Tϸ°ûÒò×Ó(T cell factor,TCF),½ø¶ø´Ù½øϸ°ûÇÖÏ®ºÍÒìÖÖÒÆÖ²·ÎÖ×ÁöµÄ½á½ÚÐγÉ[39];¶øÔÚKRASÒ°ÉúÐͽáÖ±³¦°©Ï¸°ûÖÐ,·¢ÏÖDDX3¿Éͨ¹ýDDX3/KRAS/ROS/HIF-1α/DDX3¼¶Áª·´À¡»·Ôöǿϸ°ûÇÖÏ®ÐÔ[40].ÒÔÉÏÑо¿Ã÷È·DDX3µÄÖ°©×÷ÓÃ,½âÊÍÁ˸߱í´ïDDX3½áÖ±³¦°©»¼ÕßÁÙ´²×ÜÌåÉú´æÂʽϲîµÄÔ­Òò[41].´óÐͶÓÁзÖÎö·¢Ïֵͱí´ïDDX3µÄ½áÖ±³¦°©»¼ÕßÔ¤ºóÒ²½Ï²î,ÇÒ°©Ï¸°ûÏòÔ¶´¦×ªÒƸü¼ÓƵ·±.½øÒ»²½ÊµÑé·¢Ïֵͱí´ïDDX3¿É¼¤»îSnail/E-¸ÆÕ³×ŵ°°×(E-cadherin)ÐźÅͨ·,´Ó¶ø´Ù½øÁ˽áÖ±³¦°©×ªÒÆ[42].Òò´Ë,DDX3Ò²±»ÈÏΪ¾ßÓÐÒÖ°©×÷ÓÃ.

¡¡¡¡ÔÚ·ÇСϸ°û·Î°©ÖÐ,Ó¦ÓÃÖÊÁ£¹¹½¨µÈ·½·¨,ʹE6°©µ°°×ºÍp53Í»±ä¹²Í¬ÓÕµ¼DDX3ʧ»î,MDM2/Slug/E-cadherin;¾¶¾Í±»¼¤»î,±íÏÖΪÖ×Áö¶ñÐԳ̶ÈÔö¼ÓºÍÔ¤ºó²»Á¼,·´Ó³ÁËDDX3µÄÒÖ°©×÷ÓÃ[22];¶øÔÚСϸ°û·Î°©ÖÐ,¸ß±í´ïDDX3Ó방ϸ°ûµÄ·¢Éú·¢Õ¹½ôÃÜÏà¹Ø[43].¾¡¹ÜDDX3Ôڷΰ©Öз¢»ÓË«ÖØ×÷ÓÃ,µ«Ä¿Ç°±»ÊÓΪ·Î°©µÄÖÎÁưеã,±¾Ñо¿ÈÏΪ²»Ó¦Ò»¸Å¶øÂÛ,ÁÙ´²Ó¦ÓÃÓ¦×ñÑ­¸öÌ廯¾«×¼Ò½ÁÆ.

¡¡¡¡Ôڸΰ©Ï¸°ûÖмì²âµ½¹ý±í´ïDDX3,¾­Ãª¶¨·ÇÒÀÀµÐÔÉú³¤·ÖÎö,Æä±»¼ø¶¨Îª¸Î°©·¢ÉúÖеÄת»¯»ùÒò[44];ChangµÈ[45]·¢ÏÖ,ÔÚÒÒÐ͸ÎÑײ¡¶¾(hepatitis B virus,HBV)ÑôÐÔµÄÔ­·¢ÐԸΰ©(hepatocellular carcinoma,HCC)»¼ÕßÖÐ,DDX3±í´ïˮƽ½ÏµÍ,¶øÔÚHCVÑôÐԵĻ¼ÕßÖÐÔò²»±í´ï,½øÒ»²½Í¨¹ý¼¯ÂäÐγÉʵÑéºÍÖÊÁ£¹¹½¨·¢ÏÖ,DDX3Ö÷Ҫͨ¹ýÓëÌØÒìÐÔµ°°×1(specificity protein 1,SP1)½áºÏ¶øÔöÇ¿p21(waf1/cip1)Æô¶¯×Ó»îÐÔµÄת¼À´·¢»ÓÆä¶ÔÖ×ÁöÉú³¤µÄÒÖ°©×÷ÓÃ[46].ÓÉÓÚDDX3ͬÑùÓ벡¶¾ÓÐ×ÅÖ±½Ó¹ØÁª,¹ÊÔÚÑо¿¸Î°©Ê±²»Ó¦ºöÂÔ²¡¶¾µÄЧӦ.

¡¡¡¡ÔÚ¿ÚÇ»ÁÛ״ϸ°û°©ÖÐ,·ÇÎüÑÌ»¼ÕßµÄ×éÖ¯ÃâÒß×黯Ⱦɫ±íÃ÷,µÍ±í´ïµÄDDX3ÑÏÖØÓ°Ïì×ÜÌåÉú´æÂÊ[30];¶ÔÎüÑÌ»¼Õ߶øÑÔ,¸ß±í´ïDDX3ÓëÁÜ°ÍתÒÆÏà¹Ø²¢¿ÉÔ¤²â²»Á¼Éú´æÂÊ[47].ÕâÖÖÏÖÏó¿ÉÄÜÊÇÒòΪÎüÑÌ×÷ΪһÖÖÓÕÒòÔì³ÉDDX3Í»±ä,ʹÆäÓÉÒÖ°©×ª±äΪÖ°©.

¡¡¡¡Ó«¹âËØø±¨¸æ±íÃ÷,±»HIF-1αÉϵ÷ºóµÄDDX3ͨ¹ýÓÕµ¼EMT½ø³ÌµÄ·½Ê½ÔöÇ¿ÈéÏÙ°©ÇÖÏ®[22];Ëèĸϸ°ûÁöϸ°û»îÁ¦Ôö¼ÓÔòÊÇÓÉÓÚDDX3Í»±äÓëÍ»±äµÄβ-catenin½áºÏÔö¼ÓÁËTCFÆô¶¯×ӵķ´Ê½¼¤»î[48].Ä¿Ç°,DDX3¶ÔÓÚ°©Ö¢µÄ·¢Éú·¢Õ¹Æð×Å´Ù½ø»òÒÖÖÆË«ÖØ×÷ÓÃ,Ã÷È·Á½Õß¼äµÄ¹Øϵһֱ±¸ÊܹØ×¢,ÀíÇå´Ë¹ØϵÄÜΪ°©Ö¢µÄÖÎÁÆÌṩ¸ü¶àµÄ¿ÉÐÐ;¾¶.

¡¡¡¡3.2 ¡¢DDX3Ó벡¶¾¸ÐȾµÄ¹Øϵ

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¡¡¡¡DDX3¿Éµ÷¿ØÖ×Áö¡¢²¡¶¾¸ÐȾµÈ¼²²¡µÄ·¢Éú·¢Õ¹,¾ßÓдٽø»òÒÖÖÆ°©Ï¸°û·¢Éú·¢Õ¹µÄË«ÖØ×÷ÓÃ,Ä¿Ç°±»ÈÏΪÊÇ°©Ö¢µÄÖÎÁưеã.DDX3µÄ¿¹²¡¶¾¹¦Äܼ°±¾ÉíµÄÉúÎïѧÌØÐÔ,ʹHIV¡¢HCVµÈÈ«ÇòÐÔ´«È¾ÐÔ¼²²¡µÄÖÎÁÆÓÐÁËеÄ;¾¶.Òò´ËÑз¢DDX3ÒÖÖƼÁ°ÐÏòÏà¹Ø¼²²¡µÄÖÎÁÆ,ÊÇDDX3¹«ÈϵÄÑо¿·½Ïò.Æù½ñΪֹ,ÈËÃÇͨ¹ý¶ÔDDX3²¡ÀíÉúÀíѧµÄÑо¿ÒѾ­Ñз¢³öÁËRK-33¡¢FE-15¡¢NZ51¡¢Íª¿©ËáÑΡ¢°¢Ã¹ËصȶàÖÖÒÖÖƼÁ[81,82,83,84].ÀýÈçÓ¦ÓÃ×î¶àµÄRK-33ÄܽáºÏDDX3µÄATP½áºÏÓò,´Ó¶ø×è¶ÏÆäÔڷΰ©¡¢ÓÈÎÄÊÏÈâÁö¡¢ÈéÏÙ°©¡¢½áÖ±³¦°©ºÍÇ°ÁÐÏÙ°©Ï¸°ûÖнâÐýøµÄ»îÐÔ,ͬʱRK-33¿Éʹ¸ß±í´ïDDX3°©Ï¸°ûµÄϸ°ûÖÜÆÚG1Í£ÖͺÍϸ°ûµòÍö[85,86,87,88,89].Òò´Ë,¶ÔÓÚDDX3¸ßЧÒÖÖƼÁµÄ¿ª·¢ÊÇδÀ´³¤ÆÚÄÚµÄÍ»ÆƵã,ͬʱÒÖÖƼÁµÄÑз¢·½·¨Ò²ÖµµÃÉîÈë̽¾¿.×îеÄDDX3ÒÖÖƼÁ±»Ó¦ÓÃÔÚ¿¹²¡¶¾¸ÐȾÖÐ,Ìáʾ½øÒ»²½Ñз¢Ïà¹ØÖƼÁµ÷¿ØDDX3Ò²ÊDz¡¶¾À༲²¡µÄÓÐЧÖÎÁÆ;¾¶[54,90].³ý´ËÖ®Íâ,DDX3ÊÇ·ñ²ÎÓë¸÷ÀàÐÂÐͲ¡¶¾µÄ¸ÐȾÓ븴ÖÆ,ÊÇ·ñ¿É³ÉΪÖÎÁưбê,ÖµµÃ½øÒ»²½Ì½ÌÖ.

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¡¡¡¡[1] LINDER P,JANKOWSKY E.From unwinding to clamping-the DEAD box RNA helicase family[J].Nature Reviews.Molecular Cell Biology,2011,12(8):505-516.
¡¡¡¡[2] LINDER P,LASKO P F,ASHBURNER M,et al.Birth of the D-E-A-D box[J].Nature,1989,337(6203):121-122.
¡¡¡¡[3] LINDER P,FULLER-PACE F V.Looking back on the birth of DEAD-box RNA helicases[J].Biochimica et Biophysica Acta,2013,1829(8):750-755.
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