Post-Transcriptional Control of mRNA Metabolism and Protein Secretion: The Third Level of Regulation within the NF-κB System
The NF-κB system is a key transcriptional pathway that regulates innate and adaptive immunity because it triggers the activation and differentiation processes of lymphocytes and myeloid cells during immune responses. In most instances, binding to cytoplasmic inhibitory IκB proteins sequesters NF-κB...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-08-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/10/9/2108 |
| _version_ | 1797490955700404224 |
|---|---|
| author | Jasmin Priester Jan Dreute Michael Kracht M. Lienhard Schmitz |
| author_facet | Jasmin Priester Jan Dreute Michael Kracht M. Lienhard Schmitz |
| author_sort | Jasmin Priester |
| collection | DOAJ |
| description | The NF-κB system is a key transcriptional pathway that regulates innate and adaptive immunity because it triggers the activation and differentiation processes of lymphocytes and myeloid cells during immune responses. In most instances, binding to cytoplasmic inhibitory IκB proteins sequesters NF-κB into an inactive state, while a plethora of external triggers activate three complex signaling cascades that mediate the release and nuclear translocation of the NF-κB DNA-binding subunits. In addition to these cytosolic steps (level 1 of NF-κB regulation), NF-κB activity is also controlled in the nucleus by signaling events, cofactors and the chromatin environment to precisely determine chromatin recruitment and the specificity and timing of target gene transcription (level 2 of NF-κB regulation). Here, we discuss an additional layer of the NF-κB system that manifests in various steps of post-transcriptional gene expression and protein secretion. This less-studied regulatory level allows reduction of (transcriptional) noise and signal integration and endows time-shifted control of the secretion of inflammatory mediators. Detailed knowledge of these steps is important, as dysregulated post-transcriptional NF-κB signaling circuits are likely to foster chronic inflammation and contribute to the formation and maintenance of a tumor-promoting microenvironment. |
| first_indexed | 2024-03-10T00:40:29Z |
| format | Article |
| id | doaj.art-93112042342c4e3eb21bd23aed98c14a |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T00:40:29Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-93112042342c4e3eb21bd23aed98c14a2023-11-23T15:09:16ZengMDPI AGBiomedicines2227-90592022-08-01109210810.3390/biomedicines10092108Post-Transcriptional Control of mRNA Metabolism and Protein Secretion: The Third Level of Regulation within the NF-κB SystemJasmin Priester0Jan Dreute1Michael Kracht2M. Lienhard Schmitz3Rudolf Buchheim Institute of Pharmacology, Justus Liebig University, 35392 Giessen, GermanyInstitute of Biochemistry, Justus Liebig University, 35392 Giessen, GermanyRudolf Buchheim Institute of Pharmacology, Justus Liebig University, 35392 Giessen, GermanyInstitute of Biochemistry, Justus Liebig University, 35392 Giessen, GermanyThe NF-κB system is a key transcriptional pathway that regulates innate and adaptive immunity because it triggers the activation and differentiation processes of lymphocytes and myeloid cells during immune responses. In most instances, binding to cytoplasmic inhibitory IκB proteins sequesters NF-κB into an inactive state, while a plethora of external triggers activate three complex signaling cascades that mediate the release and nuclear translocation of the NF-κB DNA-binding subunits. In addition to these cytosolic steps (level 1 of NF-κB regulation), NF-κB activity is also controlled in the nucleus by signaling events, cofactors and the chromatin environment to precisely determine chromatin recruitment and the specificity and timing of target gene transcription (level 2 of NF-κB regulation). Here, we discuss an additional layer of the NF-κB system that manifests in various steps of post-transcriptional gene expression and protein secretion. This less-studied regulatory level allows reduction of (transcriptional) noise and signal integration and endows time-shifted control of the secretion of inflammatory mediators. Detailed knowledge of these steps is important, as dysregulated post-transcriptional NF-κB signaling circuits are likely to foster chronic inflammation and contribute to the formation and maintenance of a tumor-promoting microenvironment.https://www.mdpi.com/2227-9059/10/9/2108NF-κBpost-transcriptional regulationmRNA stabilitytranslation controlncRNAprotein secretion |
| spellingShingle | Jasmin Priester Jan Dreute Michael Kracht M. Lienhard Schmitz Post-Transcriptional Control of mRNA Metabolism and Protein Secretion: The Third Level of Regulation within the NF-κB System Biomedicines NF-κB post-transcriptional regulation mRNA stability translation control ncRNA protein secretion |
| title | Post-Transcriptional Control of mRNA Metabolism and Protein Secretion: The Third Level of Regulation within the NF-κB System |
| title_full | Post-Transcriptional Control of mRNA Metabolism and Protein Secretion: The Third Level of Regulation within the NF-κB System |
| title_fullStr | Post-Transcriptional Control of mRNA Metabolism and Protein Secretion: The Third Level of Regulation within the NF-κB System |
| title_full_unstemmed | Post-Transcriptional Control of mRNA Metabolism and Protein Secretion: The Third Level of Regulation within the NF-κB System |
| title_short | Post-Transcriptional Control of mRNA Metabolism and Protein Secretion: The Third Level of Regulation within the NF-κB System |
| title_sort | post transcriptional control of mrna metabolism and protein secretion the third level of regulation within the nf κb system |
| topic | NF-κB post-transcriptional regulation mRNA stability translation control ncRNA protein secretion |
| url | https://www.mdpi.com/2227-9059/10/9/2108 |
| work_keys_str_mv | AT jasminpriester posttranscriptionalcontrolofmrnametabolismandproteinsecretionthethirdlevelofregulationwithinthenfkbsystem AT jandreute posttranscriptionalcontrolofmrnametabolismandproteinsecretionthethirdlevelofregulationwithinthenfkbsystem AT michaelkracht posttranscriptionalcontrolofmrnametabolismandproteinsecretionthethirdlevelofregulationwithinthenfkbsystem AT mlienhardschmitz posttranscriptionalcontrolofmrnametabolismandproteinsecretionthethirdlevelofregulationwithinthenfkbsystem |