Pro- and anti-apoptotic fate decisions induced by di- and trimeric synthetic cytokine receptors.

IScience
Sofie MossnerJürgen Scheller

Abstract

Synthetic strategies to activate cytokine receptors so far only address standard dimeric cytokine receptor assemblies. The 19 ligands of the tumor necrosis factor superfamily (TNFSF), however, form noncovalent trimers and receptor trimerization is considered to be essential for receptor activation. Synthetic TNFR1, TNFR2, and Fas/CD95 receptors were activated by synthetic trimeric ligands which induced NF-κB signaling or Caspase-induced apoptosis. Albeit dimeric receptor activation did not induce synthetic TNFR1 and TNFR2 signaling, dimeric FasL induced extenuated apoptosis. Simultaneous integration of dimeric Interleukin (IL-)6 receptor gp130 and trimeric Fas as synthetic cytokine receptors in one cell enabled binary cell fate decisions, gp130-mediated proliferation or Fas-mediated apoptosis. In summary, our modular fully synthetic cytokine signaling system allows precisely orchestrated cellular responses to selectively induce pro- and anti-apoptotic signaling via canonical dimeric receptors of the IL-6 family and non-canonical trimeric receptor complexes of the TNF superfamily.

References

Feb 1, 1997·Nature Biotechnology·M FischerS Rose-John
Apr 21, 1997·The Journal of Experimental Medicine·G C StarlingP A Kiener
Nov 20, 1997·The Journal of Biological Chemistry·J R OrlinickM V Chao
Apr 14, 1999·Cell Death and Differentiation·A G Porter, R U Jänicke
Feb 14, 2002·Trends in Biochemical Sciences·Jean-Luc BodmerJürg Tschopp
Jun 6, 2003·Cytokine & Growth Factor Reviews·Paul W DempseyGenhong Cheng
Sep 2, 2003·Nature Reviews. Immunology·Bharat B Aggarwal
Aug 18, 2004·Biochemical Pharmacology·Shishir Shishodia, Bharat B Aggarwal
Oct 24, 2007·Molecular & Cellular Proteomics : MCP·Ulrich RothbauerHeinrich Leonhardt
Mar 20, 2009·Nature Immunology·Nicholas S WilsonAvi Ashkenazi
Jun 17, 2009·Medical Microbiology and Immunology·Janusz WesolowskiFriedrich Koch-Nolte
Dec 17, 2009·Expert Opinion on Therapeutic Targets·Yong LinShanling Xu
May 22, 2010·Nature Reviews. Drug Discovery·Denise Faustman, Miriam Davis
Nov 2, 2011·Cellular and Molecular Life Sciences : CMLS·Sébastien TauzinPatrick Legembre
Nov 18, 2011·Current Opinion in Rheumatology·Sinisa SavicMichael F McDermott
Mar 1, 2012·Cellular Signalling·Lucía Cabal-Hierro, Pedro S Lazo
Nov 5, 2014·Nature Methods·Peter C FridyMichael P Rout
Apr 4, 2015·Cold Spring Harbor Perspectives in Biology·David R McIlwainTak W Mak
May 27, 2015·Nature Reviews. Immunology·Dirk BrennerTak W Mak
Jun 20, 2015·Trends in Biotechnology·Deboki Chakravarti, Wilson W Wong
Apr 28, 2017·Annual Review of Immunology·Kole T Roybal, Wendell A Lim
Jan 4, 2018·Science Signaling·Éva S Vanamee, Denise L Faustman
Mar 24, 2018·Science·Carl H JuneMichael C Milone
May 24, 2018·Nature Communications·Erika EngelowskiJürgen Scheller
Oct 23, 2018·Synthetic and Systems Biotechnology·Wen SiPing Wei
Oct 26, 2018·Physiological Reviews·Catherine DostertDirk Brenner
Feb 11, 2019·Trends in Immunology·Jürgen SchellerDoreen M Floss
Apr 3, 2019·Frontiers in Bioengineering and Biotechnology·Fabio CaliendoVelia Siciliano
May 18, 2019·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Nastaran Fazel ModaresJürgen Scheller
Apr 5, 2020·Cells·Éva S Vanamee, Denise L Faustman

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GraphPad Prism
SyCyR

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Apoptosis

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