Downregulated NDR1 protein kinase inhibits innate immune response by initiating an miR146a-STAT1 feedback loop

Nature Communications
Zhiyong LiuXiaojian Wang

Abstract

Interferon (IFN)-stimulated genes (ISGs) play crucial roles in the antiviral immune response; however, IFNs also induce negative regulators that attenuate the antiviral response. Here, we show that both viral and bacterial invasion downregulate Nuclear Dbf2-related kinase 1 (NDR1) expression via the type I IFN signaling pathway. NDR1 promotes the virus-induced production of type I IFN, proinflammatory cytokines and ISGs in a kinase-independent manner. NDR1 deficiency also renders mice more susceptible to viral and bacterial infections. Mechanistically, NDR1 enhances STAT1 translation by directly binding to the intergenic region of miR146a, thereby inhibiting miR146a expression and liberating STAT1 from miR146a-mediated translational inhibition. Furthermore, STAT1 binds to the miR146a promoter, thus decreasing its expression. Together, our results suggest that NDR1 promotion of STAT1 translation is an important event for IFN-dependent antiviral immune response, and suggest that NDR1 has an important role in controlling viral infections.

References

May 23, 1995·Proceedings of the National Academy of Sciences of the United States of America·T MillwardB A Hemmings
Nov 24, 1999·The Journal of Biological Chemistry·T A MillwardB A Hemmings
Aug 29, 2002·The EMBO Journal·Yoontae LeeV Narry Kim
Sep 28, 2002·Nature·Helena Santos-RosaTony Kouzarides
Dec 21, 2002·The Journal of Biological Chemistry·Rastislav TamaskovicBrian A Hemmings
Apr 12, 2006·Nature Reviews. Molecular Cell Biology·Alexander HergovichBrian A Hemmings
Jun 14, 2006·Proceedings of the National Academy of Sciences of the United States of America·Daniela C DieterichErin M Schuman
Aug 4, 2006·Proceedings of the National Academy of Sciences of the United States of America·Konstantin D TaganovDavid Baltimore
Nov 23, 2006·Current Opinion in Immunology·Takeshi Saito, Michael Gale
Feb 24, 2007·Molecular Cell·Alexander HergovichBrian A Hemmings
Jul 17, 2007·PLoS Computational Biology·Reut ShalgiYitzhak Pilpel
Dec 19, 2007·Molecular and Cellular Biology·Ru CaoYi Zhang
Jun 26, 2008·Nature Reviews. Immunology·Anthony J Sadler, Bryan R G Williams
Jul 15, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jin HouXuetao Cao
Mar 23, 2010·Cell·Osamu Takeuchi, Shizuo Akira
Apr 9, 2010·The New England Journal of Medicine·John G McHutchisonUNKNOWN PROVE3 Study Team
Jun 17, 2010·Science Signaling·Hauke CornilsBrian A Hemmings
Jan 25, 2011·Microbes and Infection·Kathryn H Richards, Andrew Macdonald
Jan 26, 2011·Molecular and Cellular Biology·Hauke CornilsBrian A Hemmings
Feb 14, 2012·Current Opinion in Virology·John W Schoggins, Charles M Rice
Apr 24, 2012·Immunity·George R Stark, James E Darnell
Jul 31, 2013·Liver International : Official Journal of the International Association for the Study of the Liver·Zhao H HouJian Zhang
Aug 13, 2013·Journal of Hepatology·Philippe MetzRalf Bartenschlager
Feb 22, 2014·Annual Review of Immunology·William M SchneiderCharles M Rice
Mar 25, 2014·Annual Review of Immunology·Jiaxi Wu, Zhijian J Chen
Jan 21, 2015·Current Biology : CB·Lei ZhangDebora Schmitz-Rohmer
Sep 22, 2015·Current Biology : CB·Carine JoffreJacques Camonis

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Datasets Mentioned

BETA
GSE55298
SRP149759

Methods Mentioned

BETA
ubiquitination
transfection
PCR
ChIP
fluorescence-activated cell sorting
Enzyme-linked immunosorbent assay
FACS
ELISA
immunoprecipition
pull-down

Software Mentioned

Graphpad
Prism

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