| First Author | Liu J | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 1136 |
| PubMed ID | 29555915 | Mgi Jnum | J:260480 |
| Mgi Id | MGI:6149468 | Doi | 10.1038/s41467-018-03530-3 |
| Citation | Liu J, et al. (2018) Peli1 negatively regulates noncanonical NF-kappaB signaling to restrain systemic lupus erythematosus. Nat Commun 9(1):1136 |
| abstractText | Systemic lupus erythematosus (SLE) is characterized by uncontrolled secretion of autoantibodies by plasma cells. Although the functional importance of plasma cells and autoantibodies in SLE has been well established, the underlying molecular mechanisms of controlling autoantibody production remain poorly understood. Here we show that Peli1 has a B cell-intrinsic function to protect against lupus-like autoimmunity in mice. Peli1 deficiency in B cells induces autoantibody production via noncanonical NF-kappaB signaling. Mechanically, Peli1 functions as an E3 ligase to associate with NF-kappaB inducing kinase (NIK) and mediates NIK Lys48 ubiquitination and degradation. Overexpression of Peli1 inhibits noncanonical NF-kappaB activation and alleviates lupus-like disease. In humans, PELI1 levels negatively correlate with disease severity in SLE patients. Our findings establish Peli1 as a negative regulator of the noncanonical NF-kappaB pathway in the context of restraining the pathogenesis of lupus-like disease. |
