Expression of death receptor 4 induces caspase-independent cell death in MMS-treated yeast

Mi Sun Kang; Sung Keun Lee; Chang Shin Park; Ju Hee Kang; Sung Ho Bae; Sung Lim Yu

doi:10.1016/j.bbrc.2008.08.159

Expression of death receptor 4 induces caspase-independent cell death in MMS-treated yeast

Mi Sun Kang, Sung Keun Lee, Chang Shin Park, Ju Hee Kang, Sung Ho Bae, Sung Lim Yu

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

7 Scopus citations

Abstract

DR4, a tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor, is a key element in the extrinsic pathway of TRAIL/TRAIL receptor-related apoptosis that exerts a preferential toxic effect against tumor cells. However, TRAIL and DR4 are expressed in various normal cells, and recent studies indicate that DR4 has a number of non-apoptotic functions. In this study, we evaluated the effects of human DR4 expression in yeast to determine the function of DR4 in normal cells. The expression of DR4 in yeast caused G1 arrest, which resulted in transient growth inhibition. Moreover, treatment of DR4-expressing yeast with a DNA damaging agent, MMS, elicited drastic, and sustained cell growth inhibition accompanied with massive apoptotic cell death. Further analysis revealed that cell death in the presence of DNA damage and DR4 expression was not dependent on the yeast caspase, YCA1. Taken together, these results indicate that DR4 triggers caspase-independent programmed cell death during the response of normal cells to DNA damage.

Original language	English
Pages (from-to)	305-309
Number of pages	5
Journal	Biochemical and Biophysical Research Communications
Volume	376
Issue number	2
DOIs	https://doi.org/10.1016/j.bbrc.2008.08.159
State	Published - 14 Nov 2008

Bibliographical note

Funding Information:
This work was supported by Korea Research Foundation Grant (KRF-2003-041-E00252) to S.-L. Yu. We appreciate Dr. D.C. Kang of Hallym University for helpful discussions and critical reading of the manuscript.

Keywords

Caspase-independent
DNA damage
DR4
Yeast

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10.1016/j.bbrc.2008.08.159

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title = "Expression of death receptor 4 induces caspase-independent cell death in MMS-treated yeast",

abstract = "DR4, a tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor, is a key element in the extrinsic pathway of TRAIL/TRAIL receptor-related apoptosis that exerts a preferential toxic effect against tumor cells. However, TRAIL and DR4 are expressed in various normal cells, and recent studies indicate that DR4 has a number of non-apoptotic functions. In this study, we evaluated the effects of human DR4 expression in yeast to determine the function of DR4 in normal cells. The expression of DR4 in yeast caused G1 arrest, which resulted in transient growth inhibition. Moreover, treatment of DR4-expressing yeast with a DNA damaging agent, MMS, elicited drastic, and sustained cell growth inhibition accompanied with massive apoptotic cell death. Further analysis revealed that cell death in the presence of DNA damage and DR4 expression was not dependent on the yeast caspase, YCA1. Taken together, these results indicate that DR4 triggers caspase-independent programmed cell death during the response of normal cells to DNA damage.",

keywords = "Caspase-independent, DNA damage, DR4, Yeast",

author = "Kang, {Mi Sun} and Lee, {Sung Keun} and Park, {Chang Shin} and Kang, {Ju Hee} and Bae, {Sung Ho} and Yu, {Sung Lim}",

note = "Funding Information: This work was supported by Korea Research Foundation Grant (KRF-2003-041-E00252) to S.-L. Yu. We appreciate Dr. D.C. Kang of Hallym University for helpful discussions and critical reading of the manuscript.",

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doi = "10.1016/j.bbrc.2008.08.159",

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AU - Kang, Mi Sun

AU - Lee, Sung Keun

AU - Park, Chang Shin

AU - Kang, Ju Hee

AU - Bae, Sung Ho

AU - Yu, Sung Lim

N1 - Funding Information: This work was supported by Korea Research Foundation Grant (KRF-2003-041-E00252) to S.-L. Yu. We appreciate Dr. D.C. Kang of Hallym University for helpful discussions and critical reading of the manuscript.

PY - 2008/11/14

Y1 - 2008/11/14

N2 - DR4, a tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor, is a key element in the extrinsic pathway of TRAIL/TRAIL receptor-related apoptosis that exerts a preferential toxic effect against tumor cells. However, TRAIL and DR4 are expressed in various normal cells, and recent studies indicate that DR4 has a number of non-apoptotic functions. In this study, we evaluated the effects of human DR4 expression in yeast to determine the function of DR4 in normal cells. The expression of DR4 in yeast caused G1 arrest, which resulted in transient growth inhibition. Moreover, treatment of DR4-expressing yeast with a DNA damaging agent, MMS, elicited drastic, and sustained cell growth inhibition accompanied with massive apoptotic cell death. Further analysis revealed that cell death in the presence of DNA damage and DR4 expression was not dependent on the yeast caspase, YCA1. Taken together, these results indicate that DR4 triggers caspase-independent programmed cell death during the response of normal cells to DNA damage.

AB - DR4, a tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor, is a key element in the extrinsic pathway of TRAIL/TRAIL receptor-related apoptosis that exerts a preferential toxic effect against tumor cells. However, TRAIL and DR4 are expressed in various normal cells, and recent studies indicate that DR4 has a number of non-apoptotic functions. In this study, we evaluated the effects of human DR4 expression in yeast to determine the function of DR4 in normal cells. The expression of DR4 in yeast caused G1 arrest, which resulted in transient growth inhibition. Moreover, treatment of DR4-expressing yeast with a DNA damaging agent, MMS, elicited drastic, and sustained cell growth inhibition accompanied with massive apoptotic cell death. Further analysis revealed that cell death in the presence of DNA damage and DR4 expression was not dependent on the yeast caspase, YCA1. Taken together, these results indicate that DR4 triggers caspase-independent programmed cell death during the response of normal cells to DNA damage.

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Expression of death receptor 4 induces caspase-independent cell death in MMS-treated yeast

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