| First Author | Hu Y | Year | 2022 |
| Journal | Cell Death Differ | Volume | 29 |
| Issue | 6 | Pages | 1176-1186 |
| PubMed ID | 34853447 | Mgi Jnum | J:344030 |
| Mgi Id | MGI:7285831 | Doi | 10.1038/s41418-021-00908-7 |
| Citation | Hu Y, et al. (2022) Bcl-3 promotes TNF-induced hepatocyte apoptosis by regulating the deubiquitination of RIP1. Cell Death Differ 29(6):1176-1186 |
| abstractText | Tumor necrosis factor-alpha (TNF) is described as a main regulator of cell survival and apoptosis in multiple types of cells, including hepatocytes. Dysregulation in TNF-induced apoptosis is associated with many autoimmune diseases and various liver diseases. Here, we demonstrated a crucial role of Bcl-3, an IkappaB family member, in regulating TNF-induced hepatic cell death. Specifically, we found that the presence of Bcl-3 promoted TNF-induced cell death in the liver, while Bcl-3 deficiency protected mice against TNF/D-GalN induced hepatoxicity and lethality. Consistently, Bcl-3-depleted hepatic cells exhibited decreased sensitivity to TNF-induced apoptosis when stimulated with TNF/CHX. Mechanistically, the in vitro results showed that Bcl-3 interacted with the deubiquitinase CYLD to synergistically switch the ubiquitination status of RIP1 and facilitate the formation of death-inducing Complex II. This complex further resulted in activation of the caspase cascade to induce apoptosis. By revealing this novel role of Bcl-3 in regulating TNF-induced hepatic cell death, this study provides a potential therapeutic target for liver diseases caused by TNF-related apoptosis. |
