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Carbon dioxide-dependent regulation of NF-κB family members RelB and p100 gives molecular insight into CO 2 -dependent immune regulation.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2017 Jul 07; Vol. 292 (27), pp. 11561-11571. Date of Electronic Publication: 2017 May 15. - Publication Year :
- 2017
-
Abstract
- CO <subscript>2</subscript> is a physiological gas normally produced in the body during aerobic respiration. Hypercapnia (elevated blood pCO <subscript>2</subscript> >≈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 CO <subscript>2</subscript> are not fully elucidated. Here, we identify several novel CO <subscript>2</subscript> -dependent changes in the NF-κB pathway. NF-κB family members p100 and RelB translocate to the nucleus in response to CO <subscript>2</subscript> A cohort of RelB protein-protein interactions ( e.g. with Raf-1 and IκBα) are altered by CO <subscript>2</subscript> exposure, although others are maintained ( e.g. with p100). RelB is processed by CO <subscript>2</subscript> 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 CO <subscript>2</subscript> Thus, we provide molecular insight into the CO <subscript>2</subscript> sensitivity of the NF-κB pathway and implicate altered RelB/p100-dependent signaling in the CO <subscript>2</subscript> -dependent regulation of inflammatory signaling.<br /> (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)
- Subjects :
- A549 Cells
Animals
Humans
Hypercapnia genetics
Hypercapnia pathology
Mice
NF-kappa B p52 Subunit genetics
Protein Domains
Signal Transduction genetics
Transcription Factor RelB genetics
Transcription, Genetic genetics
Transcription, Genetic immunology
Carbon Dioxide immunology
Hypercapnia immunology
NF-kappa B p52 Subunit immunology
Signal Transduction immunology
Transcription Factor RelB immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 292
- Issue :
- 27
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 28507099
- Full Text :
- https://doi.org/10.1074/jbc.M116.755090