TNF-related weak inducer of apoptosis receptor, a TNF receptor superfamily member, activates NF-κB through TNF receptor-associated factors

Songyi Han, Kwiyeom Yoon, Kyunghye Lee, Kyunghee Kim, Hyunduk Jang, Na Kyung Lee, Kichul Hwang, Soo Young Lee

Research output: Contribution to journalArticlepeer-review

95 Scopus citations

Abstract

TNF-related weak inducer of apoptosis (TWEAK) is a member of the TNF ligand family that induces angiogenesis in vivo. The TWEAK receptor (TweakR) is a recently identified member of the TNF receptor (TNFR) superfamily and is expressed on smooth muscle cells (SMCs) and endothelial cells (ECs). In this report we identify the TNF receptor-associated factor (TRAF) family of signal transducers as important components of TweakR-mediated NF-κB activation. Coimmunoprecipitation experiments suggested potential interactions between the cytoplasmic tail of TweakR with TRAFs 1, 2, 3, and 5. Dominant negative forms of TRAF2 and TRAF5 substantially inhibited TweakR-mediated NF-κB activation, suggesting a role of TRAFs in regulating smooth muscle and endothelial cell function. Using alanine-scanning analysis, we defined a TRAF-binding motif, PIEET, in TweakR that mediates TRAF binding and NF-κB activation. Furthermore, TweakR mutations within the TRAF-binding motif abolished TweakR-stimulated SMC migration, revealing a role for TRAFs in TweakR-induced activation events.

Original languageEnglish
Pages (from-to)789-796
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume305
Issue number4
DOIs
StatePublished - 13 Jun 2003

Keywords

  • Cell migration
  • NF-κB
  • Signal transducers
  • Smooth muscle cells
  • TRAFs
  • Tweak receptor

Fingerprint

Dive into the research topics of 'TNF-related weak inducer of apoptosis receptor, a TNF receptor superfamily member, activates NF-κB through TNF receptor-associated factors'. Together they form a unique fingerprint.

Cite this