| First Author | Liang Y | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 7 | Pages | e21696 |
| PubMed ID | 21829440 | Mgi Jnum | J:176256 |
| Mgi Id | MGI:5289762 | Doi | 10.1371/journal.pone.0021696 |
| Citation | Liang Y (2011) SHARPIN negatively associates with TRAF2-mediated NFkappaB activation. PLoS One 6(7):e21696 |
| abstractText | NFkappaB is an inducible transcriptional factor controlled by two principal signaling cascades and plays pivotal roles in diverse physiological processes including inflammation, apoptosis, oncogenesis, immunity, and development. Activation of NFkappaB signaling was detected in skin of SHAPRIN-deficient mice and can be diminished by an NFkappaB inhibitor. However, in vitro studies demonstrated that SHARPIN activates NFkappaB signaling by forming a linear ubiquitin chain assembly complex with RNF31 (HOIP) and RBCK1 (HOIL1). The inconsistency between in vivo and in vitro findings about SHARPIN's function on NFkappaB activation could be partially due to SHARPIN's potential interactions with downstream molecules of NFkappaB pathway. In this study, 17 anti-flag immunoprecipitated proteins, including TRAF2, were identified by mass spectrum analysis among Sharpin-Flag transfected mouse fibroblasts, B lymphocytes, and BALB/c LN stroma 12 cells suggesting their interaction with SHARPIN. Interaction between SHARPIN and TRAF2 confirmed previous yeast two hybridization reports that SHARPIN was one TRAF2's partners. Furthermore, luciferase-based NFkappaB reporter assays demonstrated that SHARPIN negatively associates with NFkappaB activation, which can be partly compensated by over-expression of TRAF2. These data suggested that other than activating NFkappaB signaling by forming ubiquitin ligase complex with RNF31 and RBCK1, SHARPIN may also negatively associate with NFkappaB activation via interactions with other NFkappaB members, such as TRAF2. |
