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

doi:10.1006/bbrc.2001.4369

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

Department of Life Science

Research output: Contribution to journal › Article › peer-review

27 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 language	English
Pages (from-to)	499-505
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	281
Issue number	2
DOIs	https://doi.org/10.1006/bbrc.2001.4369
State	Published - 23 Feb 2001

Bibliographical note

Funding Information:
This work was supported in part by Molecular Medical Science Research Grant 02-02-A-02 and Center of Excellence Grant 1998G0202. Y. Chung and J. Baek were supported in part by BK21 fellowship from Ministry of Education. We thank Dr. M. Bevan for the pMI retroviral vector; and Dr. H. Nakano for FLAG-tagged IKK-α expression plasmid. We are grateful to J. R. Arron for critical reading of the manuscript.

Keywords

Apoptosis
Signal transduction
TNF-R1
TRAF1
TRAF2

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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 = "Jang, {Hyun Duk} and Chung, {Young Mee} and Baik, {Ji Hyun} and Choi, {Young Geum} and Park, {Il Seon} and Jung, {Yong Keun} and Lee, {Soo Young}",

note = "Funding Information: This work was supported in part by Molecular Medical Science Research Grant 02-02-A-02 and Center of Excellence Grant 1998G0202. Y. Chung and J. Baek were supported in part by BK21 fellowship from Ministry of Education. We thank Dr. M. Bevan for the pMI retroviral vector; and Dr. H. Nakano for FLAG-tagged IKK-α expression plasmid. We are grateful to J. R. Arron for critical reading of the manuscript.",

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AU - Jang, Hyun Duk

AU - Chung, Young Mee

AU - Baik, Ji Hyun

AU - Choi, Young Geum

AU - Park, Il Seon

AU - Jung, Yong Keun

AU - Lee, Soo Young

N1 - Funding Information: This work was supported in part by Molecular Medical Science Research Grant 02-02-A-02 and Center of Excellence Grant 1998G0202. Y. Chung and J. Baek were supported in part by BK21 fellowship from Ministry of Education. We thank Dr. M. Bevan for the pMI retroviral vector; and Dr. H. Nakano for FLAG-tagged IKK-α expression plasmid. We are grateful to J. R. Arron for critical reading of the manuscript.

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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.

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

Abstract

Bibliographical note

Keywords

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