Generation of a novel proform of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein that can be reactivated by matrix metalloproteinases

Jin Na Shin; Sun Young Park; Jong Hee Cha; Jae Yoon Park; Byung Rai Lee; Sun Ah Jung; Seung Taek Lee; Cheol Won Yun; Dai Wu Seol; Tae Hyoung Kim

doi:10.1016/j.yexcr.2006.08.015

Generation of a novel proform of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein that can be reactivated by matrix metalloproteinases

Jin Na Shin, Sun Young Park, Jong Hee Cha, Jae Yoon Park, Byung Rai Lee, Sun Ah Jung, Seung Taek Lee, Cheol Won Yun, Dai Wu Seol, Tae Hyoung Kim

Department of Life Sciences

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

10 Citations (Scopus)

Abstract

TRAIL has been suggested to induce the cell death in various tumor cells but not in normal cells; however, several studies have provided the evidence that TRAIL can induce the cell death in some normal cells including human normal hepatocytes, suggesting that TRAIL may show hepatic toxicity in human. In this study, we designed a pro-form of TRAIL (sTRAIL:IL-18) in that soluble TRAIL (sTRAIL) is fused to IL-18, and a matrix metalloproteinases (MMPs) cleavage site is introduced at the connecting site. We showed that sTRAIL:IL-18 has significantly diminished the killing activity in HeLa cells but regains the activity by releasing the free sTRAIL through MMP-2-mediated cleavage. In addition, the killing activity of sTRAIL:IL-18 was significantly increased in HeLa cells when active MMP-2 was produced by TNF-α. Taken together, the data suggested that the sTRAIL:IL-18 can be reactivated at the specialized areas where MMPs are pathologically produced.

Original language	English
Pages (from-to)	3892-3898
Number of pages	7
Journal	Experimental Cell Research
Volume	312
Issue number	19
DOIs	https://doi.org/10.1016/j.yexcr.2006.08.015
Publication status	Published - 2006 Nov 15

Keywords

Cell death
Matrix metalloproteinase
TRAIL

ASJC Scopus subject areas

Cell Biology

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10.1016/j.yexcr.2006.08.015

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Shin, J. N., Park, S. Y., Cha, J. H., Park, J. Y., Lee, B. R., Jung, S. A., Lee, S. T., Yun, C. W., Seol, D. W., & Kim, T. H. (2006). Generation of a novel proform of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein that can be reactivated by matrix metalloproteinases. Experimental Cell Research, 312(19), 3892-3898. https://doi.org/10.1016/j.yexcr.2006.08.015

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title = "Generation of a novel proform of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein that can be reactivated by matrix metalloproteinases",

abstract = "TRAIL has been suggested to induce the cell death in various tumor cells but not in normal cells; however, several studies have provided the evidence that TRAIL can induce the cell death in some normal cells including human normal hepatocytes, suggesting that TRAIL may show hepatic toxicity in human. In this study, we designed a pro-form of TRAIL (sTRAIL:IL-18) in that soluble TRAIL (sTRAIL) is fused to IL-18, and a matrix metalloproteinases (MMPs) cleavage site is introduced at the connecting site. We showed that sTRAIL:IL-18 has significantly diminished the killing activity in HeLa cells but regains the activity by releasing the free sTRAIL through MMP-2-mediated cleavage. In addition, the killing activity of sTRAIL:IL-18 was significantly increased in HeLa cells when active MMP-2 was produced by TNF-α. Taken together, the data suggested that the sTRAIL:IL-18 can be reactivated at the specialized areas where MMPs are pathologically produced.",

keywords = "Cell death, Matrix metalloproteinase, TRAIL",

author = "Shin, {Jin Na} and Park, {Sun Young} and Cha, {Jong Hee} and Park, {Jae Yoon} and Lee, {Byung Rai} and Jung, {Sun Ah} and Lee, {Seung Taek} and Yun, {Cheol Won} and Seol, {Dai Wu} and Kim, {Tae Hyoung}",

note = "Funding Information: This work was supported by a grant (0220110-3 to T-H Kim) of the 2002 Korean National Cancer Control Program, Ministry of Health and Welfare, Republic of Korea.",

year = "2006",

month = nov,

day = "15",

doi = "10.1016/j.yexcr.2006.08.015",

language = "English",

volume = "312",

pages = "3892--3898",

journal = "Experimental Cell Research",

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AU - Shin, Jin Na

AU - Park, Sun Young

AU - Cha, Jong Hee

AU - Park, Jae Yoon

AU - Lee, Byung Rai

AU - Jung, Sun Ah

AU - Lee, Seung Taek

AU - Yun, Cheol Won

AU - Seol, Dai Wu

AU - Kim, Tae Hyoung

N1 - Funding Information: This work was supported by a grant (0220110-3 to T-H Kim) of the 2002 Korean National Cancer Control Program, Ministry of Health and Welfare, Republic of Korea.

PY - 2006/11/15

Y1 - 2006/11/15

N2 - TRAIL has been suggested to induce the cell death in various tumor cells but not in normal cells; however, several studies have provided the evidence that TRAIL can induce the cell death in some normal cells including human normal hepatocytes, suggesting that TRAIL may show hepatic toxicity in human. In this study, we designed a pro-form of TRAIL (sTRAIL:IL-18) in that soluble TRAIL (sTRAIL) is fused to IL-18, and a matrix metalloproteinases (MMPs) cleavage site is introduced at the connecting site. We showed that sTRAIL:IL-18 has significantly diminished the killing activity in HeLa cells but regains the activity by releasing the free sTRAIL through MMP-2-mediated cleavage. In addition, the killing activity of sTRAIL:IL-18 was significantly increased in HeLa cells when active MMP-2 was produced by TNF-α. Taken together, the data suggested that the sTRAIL:IL-18 can be reactivated at the specialized areas where MMPs are pathologically produced.

AB - TRAIL has been suggested to induce the cell death in various tumor cells but not in normal cells; however, several studies have provided the evidence that TRAIL can induce the cell death in some normal cells including human normal hepatocytes, suggesting that TRAIL may show hepatic toxicity in human. In this study, we designed a pro-form of TRAIL (sTRAIL:IL-18) in that soluble TRAIL (sTRAIL) is fused to IL-18, and a matrix metalloproteinases (MMPs) cleavage site is introduced at the connecting site. We showed that sTRAIL:IL-18 has significantly diminished the killing activity in HeLa cells but regains the activity by releasing the free sTRAIL through MMP-2-mediated cleavage. In addition, the killing activity of sTRAIL:IL-18 was significantly increased in HeLa cells when active MMP-2 was produced by TNF-α. Taken together, the data suggested that the sTRAIL:IL-18 can be reactivated at the specialized areas where MMPs are pathologically produced.

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Generation of a novel proform of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein that can be reactivated by matrix metalloproteinases

Abstract

Keywords

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