Role of SODD in regulation of tumor necrosis factor responses

Hidetoshi Takada, Nien Jung Chen, Christine Mirtsos, Shinobu Suzuki, Nobutaka Suzuki, Andrew Wakeham, Tak W. Mak, Wen Chen Yeh

Research output: Contribution to journalArticle

43 Citations (Scopus)

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-κB 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.

Original languageEnglish
Pages (from-to)4026-4033
Number of pages8
JournalMolecular and cellular biology
Volume23
Issue number11
DOIs
Publication statusPublished - Jun 2003

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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    Takada, H., Chen, N. J., Mirtsos, C., Suzuki, S., Suzuki, N., Wakeham, A., Mak, T. W., & Yeh, W. C. (2003). Role of SODD in regulation of tumor necrosis factor responses. Molecular and cellular biology, 23(11), 4026-4033. https://doi.org/10.1128/MCB.23.11.4026-4033.2003