| First Author | Sasaki Y | Year | 2008 |
| Journal | Proc Natl Acad Sci U S A | Volume | 105 |
| Issue | 31 | Pages | 10883-8 |
| PubMed ID | 18663224 | Mgi Jnum | J:139293 |
| Mgi Id | MGI:3807718 | Doi | 10.1073/pnas.0805186105 |
| Citation | Sasaki Y, et al. (2008) NIK overexpression amplifies, whereas ablation of its TRAF3-binding domain replaces BAFF:BAFF-R-mediated survival signals in B cells. Proc Natl Acad Sci U S A 105(31):10883-8 |
| abstractText | BAFF-R-dependent activation of the alternative NF-kappaB pathway plays an essential role in mature B cell survival. Mutations leading to overexpression of NIK and deletion of the TRAF3 gene are implicated in human multiple myeloma. We show that overexpression of NIK in mouse B lymphocytes amplifies alternative NF-kappaB activation and peripheral B cell numbers in a BAFF-R-dependent manner, whereas uncoupling NIK from TRAF3-mediated control causes maximal p100 processing and dramatic hyperplasia of BAFF-R-independent B cells. NIK controls alternative NF-kappaB signaling by increasing the protein levels of its negative regulator TRAF3 in a dose-dependent fashion. This mechanism keeps NIK protein levels below detection even when they cause B cell hyperplasia, so that contributions of NIK to B cell pathologies can easily be overlooked. |
