SHARPIN negatively associates with TRAF2-mediated NFκB activation.

NFκB 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 NFκB signaling was detected in skin of SHAPRIN-deficient mice and can be diminished by an NFκB inhibitor. However, in vitro studies demonstrated that activates NFκB 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 function on NFκB activation could be partially due to SHduanyu37IN's potential interactions with downstream molecules of NFκB 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 Interaction between SHduanyu37IN and TRAF2 confirmed previous yeast two hybridization reports that SHduanyu37IN was one TRAF2's partners. Furthermore, luciferase-based NFκB reporter assays demonstrated that SHduanyu37IN negatively associates with NFκB activation, which can be partly compensated by over-expression of TRAF2. These data suggested that other than activating NFκB signaling by forming ubiquitin ligase complex with RNF31 and RBCK1, SHduanyu37IN may also negatively associate with NFκB activation via interactions with other NFκB members, such as TRAF2.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}