Sox12 enhances Fbw7-mediated ubiquitination and degradation of GATA3 in Th2 cells.

Cellular & Molecular Immunology
Ken-Ichi SuehiroHiroshi Nakajima

Abstract

Allergic asthma that is caused by inhalation of house dust mites (HDMs) is mainly mediated by Th2 cells. Recently, the roles of Sox (SRY-related high-mobility-group (HMG)-box) family members in various immune responses have been investigated. However, the roles of Sox12, a member of the SoxC group, in Th2 cell differentiation and allergic airway inflammation, remain unknown. We showed that Sox12 mRNA was significantly increased during Th2 cell differentiation. In vivo, HDM-induced eosinophil infiltration into the lung and Th2 cell differentiation were exacerbated in Sox12-/- mice compared with those in control Sox12+/- mice. In vitro, Sox12-/- CD4+ T cells that were cultured under Th2 conditions had increased production of Th2 cytokines and GATA3 protein compared with those of control Sox12+/- CD4+ T cells. Importantly, forced expression of Sox12 decreased the protein levels of GATA3 in CD4+ T cells under Th2 conditions without affecting mRNA expression. Furthermore, Sox12 induced degradation of GATA3 through the proteasome pathway in CD4+ T cells. Consistently, Sox12 enhanced ubiquitination of GATA3, which was mediated by the E3 ligase Fbw7. Finally, we found that Fbw7 knockdown partly abrogated Sox12-mediated GATA3 suppressio...Continue Reading

References

Mar 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·M R Campanero, E K Flemington
Jun 25, 2005·The Journal of Biological Chemistry·Masakatsu YamashitaToshinori Nakayama
Oct 4, 2005·Nature Genetics·Ross A DickinsScott W Lowe
May 14, 2008·The Journal of Experimental Medicine·Akira SutoHiroshi Nakajima
Jul 28, 2009·The International Journal of Biochemistry & Cell Biology·Michael Wegner
Aug 4, 2009·The International Journal of Biochemistry & Cell Biology·Véronique Lefebvre
Aug 5, 2009·The International Journal of Biochemistry & Cell Biology·Alfredo I Penzo-Méndez
Mar 26, 2010·Nature Reviews. Immunology·William E Paul, Jinfang Zhu
Jul 3, 2010·Nature Communications·Pallavi BhattaramVéronique Lefebvre
Jul 28, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Daisuke KashiwakumaHiroshi Nakajima
Sep 18, 2013·Lancet·Fernando D Martinez, Donata Vercelli
Jul 31, 2014·The Journal of Experimental Medicine·Shigeru TanakaHiroshi Nakajima
Dec 19, 2014·Nature Immunology·Bart N Lambrecht, Hamida Hammad
Apr 12, 2015·The Journal of Biological Chemistry·Hiroyuki HosokawaToshinori Nakayama
May 18, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Awo A K Layman, Paula M Oliver
Dec 4, 2016·International Immunopharmacology·Si-Fa GaoDandan Lin
Aug 16, 2017·The Journal of Experimental Medicine·Takashi ItoHiroshi Nakajima
Sep 8, 2018·The Journal of Experimental Medicine·Shigeru TanakaHiroshi Nakajima

❮ Previous
Next ❯

Software Mentioned

FlowJo

Related Concepts

Related Feeds

Allergy and Asthma

Allergy and asthma are inflammatory disorders that are triggered by the activation of an allergen-specific regulatory t cell. These t cells become activated when allergens are recognized by allergen-presenting cells. Here is the latest research on allergy and asthma.