Carbon dioxide-dependent regulation of NF-κB family members RelB and p100 gives molecular insight into CO2-dependent immune regulation.

The Journal of Biological Chemistry
Ciara E KeoghEoin P Cummins

Abstract

CO2 is a physiological gas normally produced in the body during aerobic respiration. Hypercapnia (elevated blood pCO2 >≈50 mm Hg) is a feature of several lung pathologies, e.g. chronic obstructive pulmonary disease. Hypercapnia is associated with increased susceptibility to bacterial infections and suppression of inflammatory signaling. The NF-κB pathway has been implicated in these effects; however, the molecular mechanisms underpinning cellular sensitivity of the NF-κB pathway to CO2 are not fully elucidated. Here, we identify several novel CO2-dependent changes in the NF-κB pathway. NF-κB family members p100 and RelB translocate to the nucleus in response to CO2 A cohort of RelB protein-protein interactions (e.g. with Raf-1 and IκBα) are altered by CO2 exposure, although others are maintained (e.g. with p100). RelB is processed by CO2 in a manner dependent on a key C-terminal domain located in its transactivation domain. Loss of the RelB transactivation domain alters NF-κB-dependent transcriptional activity, and loss of p100 alters sensitivity of RelB to CO2 Thus, we provide molecular insight into the CO2 sensitivity of the NF-κB pathway and implicate altered RelB/p100-dependent signaling in the CO2-dependent regulation of i...Continue Reading

References

Feb 26, 2003·American Journal of Respiratory Cell and Molecular Biology·Kei TakeshitaKazuhiro Yamaguchi
Jul 23, 2003·The Journal of Biological Chemistry·Harald Jakob MaierBernd Baumann
Sep 6, 2003·American Journal of Respiratory and Critical Care Medicine·John G LaffeyPaul McLoughlin
Jan 27, 2004·Nature Cell Biology·Tewis BouwmeesterGiulio Superti-Furga
Jun 16, 2006·Respiratory Medicine·Fionnuala CrummyMatthew T Naughton
Aug 5, 2006·Journal of Applied Physiology·Guangyu LiGabriel G Haddad
Dec 22, 2006·Nature Reviews. Molecular Cell Biology·Neil D Perkins
Jan 27, 2007·Cell·Soumen BasakAlexander Hoffmann
Sep 18, 2007·Journal of Molecular Biology·Anu K MoorthyGourisankar Ghosh
Jun 17, 2008·Critical Care Medicine·Donall F O'CroininPaul McLoughlin
Jan 13, 2009·American Journal of Physiology. Lung Cellular and Molecular Physiology·Mohammad AbolhassaniLaurent Schwartz
Feb 25, 2009·Proceedings of the National Academy of Sciences of the United States of America·Kfir SharabiYosef Gruenbaum
Jun 18, 2009·Critical Care Medicine·Joseph CostelloJohn G Laffey
Oct 23, 2009·Proceedings of the National Academy of Sciences of the United States of America·Iiro Taneli HeleniusGreg J Beitel
Nov 10, 2009·Proceedings of the National Academy of Sciences of the United States of America·Stephan HailfingerMargot Thome
Feb 26, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Naizhen WangPeter H S Sporn
May 13, 2010·The Journal of Biological Chemistry·Toshio TandoHideo Iba
Sep 8, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Eoin P CumminsCormac T Taylor
Jan 13, 2011·The Journal of Physiology·Cormac T Taylor, Eoin P Cummins
May 26, 2011·Critical Care Medicine·Gail Otulakowski, Brian P Kavanagh
Aug 30, 2011·Proceedings of the National Academy of Sciences of the United States of America·Stephan HailfingerMargot Thome
Mar 8, 2012·The Journal of Biological Chemistry·Kathryn M OliverEoin P Cummins
Mar 23, 2012·Immunological Reviews·Sankar Ghosh, Matthew S Hayden
Aug 17, 2012·Cell Cycle·Marina M BelletPaolo Sassone-Corsi
Jun 20, 2013·American Journal of Respiratory Cell and Molecular Biology·Khalilah L GatesPeter H S Sporn
Aug 8, 2013·Journal of Leukocyte Biology·Patrick MilletBarbra Yoza
Sep 21, 2013·Cellular and Molecular Life Sciences : CMLS·Eoin P CumminsCormac T Taylor
Mar 13, 2014·Journal of Cellular Biochemistry·Julia LeidnerRalf B Marienfeld
Aug 3, 2014·The Journal of Physiology·Gail OtulakowskiBrian P Kavanagh
Oct 29, 2014·Proceedings of the National Academy of Sciences of the United States of America·Zhihua TaoGourisankar Ghosh
Jan 13, 2015·The Journal of Surgical Research·Yuan-Sheng TzengShi-Jye Chu

❮ Previous
Next ❯

Citations

Sep 21, 2019·Physiological Reviews·Eoin P CumminsCormac T Taylor
Apr 11, 2020·American Journal of Respiratory Cell and Molecular Biology·Ankit BharatJacob I Sznajder
Oct 9, 2020·Journal of Clinical Medicine·Masahiko ShigemuraJacob I Sznajder
Dec 18, 2020·Frontiers in Physiology·Masahiko ShigemuraJacob I Sznajder
Feb 27, 2021·Interface Focus·D E PhelanE P Cummins
Feb 26, 2021·Interface Focus·Claire MastersonDaniel O'Toole
Apr 11, 2021·Respiratory Research·David SchnebergerShelley Kirychuk
Sep 25, 2021·Science Advances·Victoria L LinthwaiteMartin J Cann
Jul 1, 2021·American Journal of Respiratory Cell and Molecular Biology·Vitalii KryvenkoIstván Vadász
Jul 8, 2021·Pediatric Research·Sie Kei WongE J Molloy

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

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.