Deletion of the RNA-binding proteins ZFP36L1 and ZFP36L2 leads to perturbed thymic development and T lymphoblastic leukemia.

Nature Immunology
Daniel J HodsonMartin Turner

Abstract

ZFP36L1 and ZFP36L2 are RNA-binding proteins (RBPs) that interact with AU-rich elements in the 3' untranslated region of mRNA, which leads to mRNA degradation and translational repression. Here we show that mice that lacked ZFP36L1 and ZFP36L2 during thymopoiesis developed a T cell acute lymphoblastic leukemia (T-ALL) dependent on the oncogenic transcription factor Notch1. Before the onset of T-ALL, thymic development was perturbed, with accumulation of cells that had passed through the beta-selection checkpoint without first expressing the T cell antigen receptor beta-chain (TCRbeta). Notch1 expression was higher in untransformed thymocytes in the absence of ZFP36L1 and ZFP36L2. Both RBPs interacted with evolutionarily conserved AU-rich elements in the 3' untranslated region of Notch1 and suppressed its expression. Our data establish a role for ZFP36L1 and ZFP36L2 during thymocyte development and in the prevention of malignant transformation.

References

Oct 19, 1999·The Journal of Experimental Medicine·S WinandyK Georgopoulos
Jun 3, 2000·Nature Genetics·C I RodríguezS M Dymecki
Sep 11, 2002·Seminars in Immunology·Alison M Michie, Juan Carlos Zúñiga-Pflücker
Jan 28, 2003·European Journal of Immunology·Jasper de BoerDimitris Kioussis
Feb 26, 2004·Nature Structural & Molecular Biology·Brian P HudsonPeter E Wright
Nov 13, 2004·The EMBO Journal·Martin SchmidlinChristoph Moroni
Aug 2, 2005·Nature Immunology·Maria Ciofani, Juan Carlos Zúñiga-Pflücker
Sep 17, 2005·Blood·Jennifer O'NeilA Thomas Look
Dec 16, 2005·Molecular and Cellular Biology·Alexis DumortierSusan Chan
Oct 3, 2006·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Sarah E BellMartin Turner
Dec 19, 2006·Cell Cycle·Roger S JacksonPeng Liang
Jan 5, 2007·Proceedings of the National Academy of Sciences of the United States of America·Foster C Gonsalves, David A Weisblat
Jun 19, 2007·Nature Reviews. Genetics·Jack D Keene
Jun 30, 2007·The EMBO Journal·April P KellyDoreen A Cantrell
Sep 18, 2007·Nature Medicine·Teresa PalomeroAdolfo A Ferrando
Oct 6, 2007·Expert Opinion on Biological Therapy·Don Benjamin, Christoph Moroni
Nov 28, 2007·Annual Review of Pathology·Jon C AsterStephen C Blacklow
Dec 22, 2007·Nature Reviews. Immunology·Ellen V RothenbergMary A Yui
Apr 17, 2008·Cell Cycle·Teresa PalomeroAdolfo A Ferrando
Sep 2, 2008·Oncogene·R M DemarestA J Capobianco
Nov 5, 2008·The Journal of Experimental Medicine·Xiaoyu LiHarald von Boehmer
Dec 18, 2008·Blood·Celine DumontVictor L J Tybulewicz
Dec 24, 2008·Proceedings of the National Academy of Sciences of the United States of America·Constantin GeorgescuEllen V Rothenberg
May 21, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Olympia PapadakiDimitris L Kontoyiannis
Jun 13, 2009·Blood·Jon C Aster
Nov 13, 2009·Nature·Raymond E MoelleringJames E Bradner
Nov 17, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Emma FioriniH Robson Macdonald
Jan 26, 2010·Nature Reviews. Immunology·Ryan M O'ConnellDavid Baltimore

❮ Previous
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Citations

Aug 9, 2013·Current Diabetes Reports·Joachim Storling, Caroline Anna Brorsson
Jul 21, 2010·Nature Immunology·Jelena Nedjic, Iannis Aifantis
Aug 13, 2011·Molecular Biology of the Cell·Agnès Desroches-CastanDelphine Ciais
Nov 13, 2010·Nucleic Acids Research·Andreas R GruberIvo L Hofacker
Jun 5, 2004·BMC Biology·Tony Chih Yuan ChuangSabine Mai
Jan 24, 2013·PloS One·Karine TréguerPierre Thiébaud
May 17, 2014·PloS One·Christopher B BallSilvia B V Ramos
Jul 1, 2014·PloS One·Boris ReznikJens Lykke-Andersen
Jan 10, 2014·Genome Biology·Neelanjan MukherjeeUwe Ohler
May 21, 2014·Nature Immunology·Panagiota KafaslaDimitris L Kontoyiannis
May 21, 2014·Nature Immunology·Martin TurnerElena Vigorito
Apr 16, 2014·Proceedings of the National Academy of Sciences of the United States of America·Frederick E Tan, Michael B Elowitz
May 30, 2014·Genes and Immunity·S S AmundsenB A Lie
Sep 13, 2012·Cellular and Molecular Life Sciences : CMLS·Delphine CiaisJean-Jacques Feige
Apr 1, 2015·Proceedings of the National Academy of Sciences of the United States of America·Xing ChangAnjana Rao
Jul 24, 2015·Clinical and Experimental Immunology·R NewmanM Turner
Feb 14, 2012·Current Opinion in Immunology·Martin Turner, Daniel Hodson
Aug 2, 2011·Trends in Molecular Medicine·Sung-Hee Chang, Timothy Hla
Mar 27, 2015·Biophysical Journal·Brittany R MorganFrancesca Massi
Oct 6, 2015·Nature Genetics·Keisuke KataokaSeishi Ogawa
Apr 5, 2013·Immunological Reviews·Joan Yuan, Stefan A Muljo
Jul 5, 2012·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Panagiota KafaslaDimitris L Kontoyiannis
Dec 22, 2011·Molecular Systems Biology·Franz KratochvillPavel Kovarik
Apr 15, 2014·Genes, Chromosomes & Cancer·Adrien CossonUNKNOWN Groupe Francophone de Cytogénétique Hématologique
Nov 14, 2015·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·J-G ZhuW-D Zhong
Apr 23, 2016·Science·Alison GallowayMartin Turner
Aug 7, 2012·Cell·Robert J RounbehlerJohn L Cleveland
Sep 16, 2011·Blood·Maria BaouJohn J Murphy
May 21, 2016·Frontiers in Immunology·Koelina GangulyNooruddin Khan
Feb 2, 2017·Leukemia & Lymphoma·Stefan NagelHans G Drexler
Nov 7, 2015·Scientific Reports·Ming-Tai ChenJun-Wu Zhang
May 19, 2017·Nature Immunology·Palaniraja ThandapaniIannis Aifantis
Sep 2, 2018·Immunology and Cell Biology·Pierre C McCarthyJ Simon C Arthur
Jul 28, 2016·Nature Reviews. Cancer·Laura Belver, Adolfo Ferrando

❮ Previous
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