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

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

Research output: Contribution to journalArticle

26 Citations (Scopus)

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

Fingerprint

TNF Receptor-Associated Factor 1
TNF Receptor-Associated Factor 2
Cell death
Caspases
Cell Death
Tumor Necrosis Factor-alpha
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
T-cells
Caspase 8
Hybridomas

Keywords

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

Cite this

Jang, Hyunduk ; Chung, Young Mee ; Baik, Ji Hyun ; Choi, Young Geum ; Park, Il Seon ; Jung, Yong Keun ; Lee, Soo Young. / Caspase-cleaved TRAF1 negatively regulates the antiapoptotic signals of TRAF2 during TNF-induced cell death. In: Biochemical and Biophysical Research Communications. 2001 ; Vol. 281, No. 2. pp. 499-505.
@article{54a1af08778b4d6e9f9a8659355d9e87,
title = "Caspase-cleaved TRAF1 negatively regulates the antiapoptotic signals of TRAF2 during TNF-induced cell death",
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.",
keywords = "Apoptosis, Signal transduction, TNF-R1, TRAF1, TRAF2",
author = "Hyunduk Jang and Chung, {Young Mee} and Baik, {Ji Hyun} and Choi, {Young Geum} and Park, {Il Seon} and Jung, {Yong Keun} and Lee, {Soo Young}",
year = "2001",
month = "2",
day = "23",
doi = "10.1006/bbrc.2001.4369",
language = "English",
volume = "281",
pages = "499--505",
journal = "Biochemical and biophysical research communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "2",

}

Caspase-cleaved TRAF1 negatively regulates the antiapoptotic signals of TRAF2 during TNF-induced cell death. / Jang, Hyunduk; Chung, Young Mee; Baik, Ji Hyun; Choi, Young Geum; Park, Il Seon; Jung, Yong Keun; Lee, Soo Young.

In: Biochemical and Biophysical Research Communications, Vol. 281, No. 2, 23.02.2001, p. 499-505.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Caspase-cleaved TRAF1 negatively regulates the antiapoptotic signals of TRAF2 during TNF-induced cell death

AU - Jang, Hyunduk

AU - Chung, Young Mee

AU - Baik, Ji Hyun

AU - Choi, Young Geum

AU - Park, Il Seon

AU - Jung, Yong Keun

AU - Lee, Soo Young

PY - 2001/2/23

Y1 - 2001/2/23

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Signal transduction

KW - TNF-R1

KW - TRAF1

KW - TRAF2

UR - http://www.scopus.com/inward/record.url?scp=0034803045&partnerID=8YFLogxK

U2 - 10.1006/bbrc.2001.4369

DO - 10.1006/bbrc.2001.4369

M3 - Article

C2 - 11181075

AN - SCOPUS:0034803045

VL - 281

SP - 499

EP - 505

JO - Biochemical and biophysical research communications

JF - Biochemical and biophysical research communications

SN - 0006-291X

IS - 2

ER -