| First Author | Sun J | Year | 2016 |
| Journal | Cell Rep | Volume | 14 |
| Issue | 4 | Pages | 737-749 |
| PubMed ID | 26776519 | Mgi Jnum | J:244814 |
| Mgi Id | MGI:5913593 | Doi | 10.1016/j.celrep.2015.12.069 |
| Citation | Sun J, et al. (2016) The 11S Proteasome Subunit PSME3 Is a Positive Feedforward Regulator of NF-kappaB and Important for Host Defense against Bacterial Pathogens. Cell Rep 14(4):737-749 |
| abstractText | The NF-kappaB pathway plays important roles in immune responses. Although its regulation has been extensively studied, here, we report an unknown feedforward mechanism for the regulation of this pathway by Toll-like receptor (TLR) ligands in macrophages. During bacterial infections, TLR ligands upregulate the expression of the 11S proteasome subunit PSME3 via NF-kappaB-mediated transcription in macrophages. PSME3, in turn, enhances the transcriptional activity of NF-kappaB by directly binding to and destabilizing KLF2, a negative regulator of NF-kappaB transcriptional activity. Consistent with this positive role of PSME3 in NF-kappaB regulation and importance of the NF-kappaB pathway in host defense against bacterial infections, the lack of PSME3 in hematopoietic cells renders the hosts more susceptible to bacterial infections, accompanied by increased bacterial burdens in host tissues. Thus, this study identifies a substrate for PSME3 and elucidates a proteolysis-dependent, but ubiquitin-independent, mechanism for NF-kappaB regulation that is important for host defense and innate immunity. |
