Caspase-cleaved TRAF1 negatively regulates the antiapoptotic signals of TRAF2 during TNF-induced cell death

Hyun Duk Jang, Young Mee Chung, Ji Hyun Baik, Young Geum Choi, Il Seon Park, Yong Keun Jung, Soo Young Lee

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Tumor necrosis factor (TNF) signaling leads to pleiotropic responses in a wide range of cell types, in part by activating antiapoptotic and proapoptotic pathways. Previous studies have suggested that TNF receptor-associated factor (TRAF) 2 can mediate crucial antiapoptotic signals during TNF stimulation. However, it is unclear how the antiapoptotic signals via TRAF2 in TNF-R1 signaling is regulated. Here we show that TRAF1 is cleaved by caspase-8 into two fragments during apoptosis induced by TNF. Overexpression of the C-terminal cleavage product, TRAF1-c, increased TNF-induced cell death of hybridoma T cells. Importantly, we demonstrate that the cleavage product of TRAF1 coimmunoprecipitates with TRAF2 that is released from the TNF-R1 complex in response to prolonged TNF treatment. These results indicate that caspase-dependent cleavage of TRAF1 generates TRAF1-c fragments that are able to bind TRAF2, and then sequester TRAF2 from the TNF-R1 complex, rendering cells, at least in part, sensitive to TNF.

Original languageEnglish
Pages (from-to)499-505
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume281
Issue number2
DOIs
StatePublished - 23 Feb 2001

Keywords

  • Apoptosis
  • Signal transduction
  • TNF-R1
  • TRAF1
  • TRAF2

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