Trim58 degrades Dynein and regulates terminal erythropoiesis.
Trim58 degrades Dynein and regulates terminal erythropoiesis.
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DOI：
10.1016/j.devcel.2014.07.021
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发表时间：
2014-09-29
影响因子：
11.8
通讯作者：
Weiss MJ
中科院分区：
文献类型：
--
作者：
Thom CS;Traxler EA;Khandros E;Nickas JM;Zhou OY;Lazarus JE;Silva AP;Prabhu D;Yao Y;Aribeana C;Fuchs SY;Mackay JP;Holzbaur EL;Weiss MJ
TRIM 58是E3泛素连接酶超家族成员，其被全基因组关联研究（GWAS）牵连以调节人类红细胞性状。在这里，我们表明，Trim 58的表达是在晚期红细胞生成过程中诱导的，并且其通过shRNA的消耗抑制了晚期有核成红细胞向无核网织红细胞的成熟。成像流式细胞术研究表明，Trim 58调节成红细胞核的极化和/或挤出。在体外，Trim 58直接结合并泛素化微管运动动力蛋白的中间链。在细胞中，Trim 58刺激动力蛋白全蛋白复合物的蛋白酶体依赖性降解。在红细胞生成过程中，Trim 58表达、动力蛋白丢失和去核同时发生，并且都被Trim 58 shRNA抑制。动力蛋白调节核定位和微管组织，这两者在成红细胞去核过程中都发生了巨大的变化。因此，我们认为Trim 58通过消除动力蛋白来调节这一过程。我们的研究结果确定了一个红细胞特异性的去核调节因子，并阐明了一个以前未被认识的控制动力蛋白活性的机制。
TRIM58 is an E3 ubiquitin ligase superfamily member implicated by genome wide association studies (GWAS) to regulate human erythrocyte traits. Here we show that Trim58 expression is induced during late erythropoiesis and that its depletion by shRNAs inhibits the maturation of late stage nucleated erythroblasts to anucleate reticulocytes. Imaging flow cytometry studies demonstrate that Trim58 regulates polarization and/or extrusion of erythroblast nuclei. In vitro, Trim58 directly binds and ubiquitinates the intermediate chain of the microtubule motor dynein. In cells, Trim58 stimulates proteasome-dependent degradation of the dynein holoprotein complex. During erythropoiesis, Trim58 expression, dynein loss and enucleation occur concomitantly and all are inhibited by Trim58 shRNAs. Dynein regulates nuclear positioning and microtubule organization, both of which undergo dramatic changes during erythroblast enucleation. Thus, we propose that Trim58 regulates this process by eliminating dynein. Our findings identify an erythroid-specific regulator of enucleation and elucidate a previously unrecognized mechanism for controlling dynein activity.
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影响因子：
2.6
作者：
Chen, CY;Pajak, L;Koury, ST
通讯作者：
Koury, ST
影响因子：
20.3
作者：
Konstantinidis, Diamantis G.;Pushkaran, Suvarnamala;Kalfa, Theodosia A.
通讯作者：
Kalfa, Theodosia A.
DOI：
10.1073/pnas.0609174104
发表时间：
2007-04-10
影响因子：
11.1
作者：
James, Leo C.;Keeble, Anthony H.;Trowsdale, John
通讯作者：
Trowsdale, John
影响因子：
64.8
作者：
Gieger, Christian;Radhakrishnan, Aparna;Cvejic, Ana;Tang, Weihong;Porcu, Eleonora;Pistis, Giorgio;Serbanovic-Canic, Jovana;Elling, Ulrich;Goodall, Alison H.;Labrune, Yann;Lopez, Lorna M.;Maegi, Reedik;Meacham, Stuart;Okada, Yukinori;Pirastu, Nicola;Sorice, Rossella;Teumer, Alexander;Voss, Katrin;Zhang, Weihua;Ramirez-Solis, Ramiro;Bis, Joshua C.;Ellinghaus, David;Goegele, Martin;Hottenga, Jouke-Jan;Langenberg, Claudia;Kovacs, Peter;O'Reilly, Paul F.;Shin, So-Youn;Esko, Toenu;Hartiala, Jaana;Kanoni, Stavroula;Murgia, Federico;Parsa, Afshin;Stephens, Jonathan;van der Harst, Pim;van der Schoot, C. Ellen;Allayee, Hooman;Attwood, Antony;Balkau, Beverley;Bastardot, Francois;Basu, Saonli;Baumeister, Sebastian E.;Biino, Ginevra;Bomba, Lorenzo;Bonnefond, Amelie;Cambien, Francois;Chambers, John C.;Cucca, Francesco;D'Adamo, Pio;Davies, Gail;de Boer, Rudolf A.;de Geus, Eco J. C.;Doering, Angela;Elliott, Paul;Erdmann, Jeanette;Evans, David M.;Falchi, Mario;Feng, Wei;Folsom, Aaron R.;Frazer, Ian H.;Gibson, Quince D.;Glazer, Nicole L.;Hammond, Chris;Hartikainen, Anna-Liisa;Heckbert, Susan R.;Hengstenberg, Christian;Hersch, Micha;Illig, Thomas;Loos, Ruth J. F.;Jolley, Jennifer;Khaw, Kay Tee;Kuehnel, Brigitte;Kyrtsonis, Marie-Christine;Lagou, Vasiliki;Lloyd-Jones, Heather;Lumley, Thomas;Mangino, Massimo;Maschio, Andrea;Leach, Irene Mateo;McKnight, Barbara;Memari, Yasin;Mitchell, Braxton D.;Montgomery, Grant W.;Nakamura, Yusuke;Nauck, Matthias;Navis, Gerjan;Noethlings, Ute;Nolte, Ilja M.;Porteous, David J.;Pouta, Anneli;Pramstaller, Peter P.;Pullat, Janne;Ring, Susan M.;Rotter, Jerome I.;Ruggiero, Daniela;Ruokonen, Aimo;Sala, Cinzia;Samani, Nilesh J.;Sambrook, Jennifer;Schlessinger, David;Schreiber, Stefan;Schunkert, Heribert;Scott, James;Smith, Nicholas L.;Snieder, Harold;Starr, John M.;Stumvoll, Michael;Takahashi, Atsushi;Tang, W. H. Wilson;Taylor, Kent;Tenesa, Albert;Thein, Swee Lay;Toenjes, Anke;Uda, Manuela;Ulivi, Sheila;van Veldhuisen, Dirk J.;Visscher, Peter M.;Voelker, Uwe;Wichmann, H-Erich;Wiggins, Kerri L.;Willemsen, Gonneke;Yang, Tsun-Po;Zhao, Jing Hua;Zitting, Paavo;Bradley, John R.;Dedoussis, George V.;Gasparini, Paolo;Hazen, Stanley L.;Metspalu, Andres;Pirastu, Mario;Shuldiner, Alan R.;van Pelt, L. Joost;Zwaginga, Jaap-Jan;Boomsma, Dorret I.;Deary, Ian J.;Franke, Andre;Froguel, Philippe;Ganesh, Santhi K.;Jarvelin, Marjo-Riitta;Martin, Nicholas G.;Meisinger, Christa;Psaty, Bruce M.;Spector, Timothy D.;Wareham, Nicholas J.;Akkerman, Jan-Willem N.;Ciullo, Marina;Deloukas, Panos;Greinacher, Andreas;Jupe, Steve;Kamatani, Naoyuki;Khadake, Jyoti;Kooner, Jaspal S.;Penninger, Josef;Prokopenko, Inga;Stemple, Derek;Toniolo, Daniela;Wernisch, Lorenz;Sanna, Serena;Hicks, Andrew A.;Rendon, Augusto;Ferreira, Manuel A.;Ouwehand, Willem H.;Soranzo, Nicole
通讯作者：
Soranzo, Nicole
影响因子：
20.3
作者：
Keerthivasan, Ganesan;Small, Sara;Crispino, John D.
通讯作者：
Crispino, John D.