Alternative splicing factor/splicing factor 2 regulates the expression of the zeta subunit of the human T cell receptor-associated CD3 complex.

The Journal of Biological Chemistry
Vaishali R Moulton, George C Tsokos

Abstract

T cells from patients with systemic lupus erythematosus express decreased levels of the T cell receptor-associated CD3 zeta chain, a feature directly linked to their aberrant function. The decrease in CD3zeta protein expression is in part due to decreased levels of functional wild type isoform of the 3'-untranslated region (UTR) of CD3zeta mRNA with concomitant increased levels of an unstable alternatively spliced isoform. In order to identify factors involved in the post-transcriptional regulation of CD3zeta, we performed mass spectrometric analysis of Jurkat T cell nuclear proteins "pulled down" by a CD3zeta 3'-UTR oligonucleotide, which identified the splicing protein alternative splicing factor/splicing factor 2 (ASF/SF2). We show for the first time that ASF/SF2 binds specifically to the 3'-UTR of CD3zeta and regulates expression of CD3zeta protein by limiting the production of the alternatively spliced isoform. During activation of human T cells, an increase in the wild type CD3zeta mRNA is associated with increased expression of ASF/SF2. Finally, we show a significant correlation between ASF/SF2 and CD3zeta protein levels in T cells from systemic lupus erythematosus patients. Thus, our results identify ASF/SF2 as a novel ...Continue Reading

References

Dec 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·A M WeissmanR D Klausner
Nov 1, 1982·Arthritis and Rheumatism·E M TanR J Winchester
Jan 28, 1994·Cell·A Weiss, D R Littman
Dec 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·K L MoserJ B Harley
Mar 26, 1999·European Journal of Immunology·R LemaireR Lafyatis
Jan 22, 2002·The Journal of Biological Chemistry·Vita Dauksaite, Göran Akusjärvi
Oct 9, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Klaus TenbrockGeorge C Tsokos
Mar 11, 2003·Annual Review of Biochemistry·Douglas L Black
Sep 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sandeep KrishnanGeorge C Tsokos
Dec 9, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mariano Sanchez-LockhartJim Miller
Feb 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jin Gene WangJeffrey R Bender
Nov 23, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Bhabadeb ChowdhuryGeorge C Tsokos
Jan 24, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yansong LiGeorge C Tsokos
Feb 21, 2007·Nature Structural & Molecular Biology·Rotem KarniAdrian R Krainer
May 29, 2008·The Journal of Biological Chemistry·Vaishali R MoultonGeorge C Tsokos
Jun 21, 2008·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Robert A CohenIsaac E Stillman
Jan 27, 2009·Autoimmunity Reviews·Brian D PooleJudith A James
Sep 1, 2009·The Journal of Pathology·Sarah MoleSheila V Graham

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Citations

Jan 16, 2013·Proceedings of the National Academy of Sciences of the United States of America·Vaishali R MoultonGeorge C Tsokos
Jul 2, 2011·Current Opinion in Rheumatology·Vasileios C Kyttaris, George C Tsokos
Dec 12, 2012·Journal of Hematology & Oncology·Xianfeng ZhaYangqiu Li
Apr 5, 2011·Arthritis Research & Therapy·Vaishali R Moulton, George C Tsokos
Oct 27, 2011·PLoS Pathogens·Martin LarsenGuy Gorochov
Dec 26, 2015·International Journal of Molecular Sciences·Mehmet YabasGerard F Hoyne
May 12, 2015·The Journal of Clinical Investigation·Vaishali R Moulton, George C Tsokos
Mar 25, 2015·Lupus·D ComteG C Tsokos
Jun 11, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·William F HawsePenelope A Morel
Sep 20, 2018·Diabetes, Obesity & Metabolism·Maria Inês AlvelosDécio L Eizirik
Jun 6, 2018·Frontiers in Immunology·Takayuki KatsuyamaVaishali R Moulton
Sep 6, 2019·The Journal of Clinical Investigation·Takayuki KatsuyamaVaishali R Moulton
Jul 23, 2014·Current Opinion in Rheumatology·Christine KonyaGeorge C Tsokos
Aug 19, 2020·Rheumatology·Takayuki KatsuyamaVaishali R Moulton
May 9, 2014·Molecular Cancer Research : MCR·Shipra Das, Adrian R Krainer
Jul 8, 2021·Cell Reports·Takayuki Katsuyama, Vaishali R Moulton

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