Role of SODD in regulation of tumor necrosis factor responses |
| |
Authors: | Takada Hidetoshi Chen Nien-Jung Mirtsos Christine Suzuki Shinobu Suzuki Nobutaka Wakeham Andrew Mak Tak W Yeh Wen-Chen |
| |
Affiliation: | Advanced Medical Discovery Institute, University Health Network, Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M5G 2C1. |
| |
Abstract: | Signaling from tumor necrosis factor receptor type 1 (TNFR1) can elicit potent inflammatory and cytotoxic responses that need to be properly regulated. It was suggested that the silencer of death domains (SODD) protein constitutively associates intracellularly with TNFR1 and inhibits the recruitment of cytoplasmic signaling proteins to TNFR1 to prevent spontaneous aggregation of the cytoplasmic death domains of TNFR1 molecules that are juxtaposed in the absence of ligand stimulation. In this study, we demonstrate that mice lacking SODD produce larger amounts of cytokines in response to in vivo TNF challenge. SODD-deficient macrophages and embryonic fibroblasts also show altered responses to TNF. TNF-induced activation of NF-kappaB is accelerated in SODD-deficient cells, but TNF-induced c-Jun N-terminal kinase activity is slightly repressed. Interestingly, the apoptotic arm of TNF signaling is not hyperresponsive in the SODD-deficient cells. Together, these results suggest that SODD is critical for the regulation of TNF signaling. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|