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

Research output: Contribution to journalArticle

8 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 languageEnglish
Pages (from-to)3892-3898
Number of pages7
JournalExperimental Cell Research
Volume312
Issue number19
DOIs
Publication statusPublished - 2006 Nov 15

Fingerprint

TNF-Related Apoptosis-Inducing Ligand
Interleukin-18
Matrix Metalloproteinases
Tumor Necrosis Factor-alpha
Apoptosis
Ligands
Matrix Metalloproteinase 2
HeLa Cells
Cell Death
Hepatocytes
Liver
Neoplasms

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Shin, Jin Na ; Park, Sun Young ; Cha, Jong Hee ; Park, Jae Yoon ; Lee, Byung Rai ; Jung, Sun Ah ; Lee, Seung-Taek ; Yun, Cheol Won ; Seol, Dai Wu ; Kim, Tae Hyoung. / Generation of a novel proform of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein that can be reactivated by matrix metalloproteinases. In: Experimental Cell Research. 2006 ; Vol. 312, No. 19. pp. 3892-3898.
@article{41169042f7f845ef8f07469f15b46157,
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.",
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 Seung-Taek Lee and Yun, {Cheol Won} and Seol, {Dai Wu} and Kim, {Tae Hyoung}",
year = "2006",
month = "11",
day = "15",
doi = "10.1016/j.yexcr.2006.08.015",
language = "English",
volume = "312",
pages = "3892--3898",
journal = "Experimental Cell Research",
issn = "0014-4827",
publisher = "Academic Press Inc.",
number = "19",

}

Generation of a novel proform of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein that can be reactivated by matrix metalloproteinases. / Shin, Jin Na; Park, Sun Young; Cha, Jong Hee; Park, Jae Yoon; Lee, Byung Rai; Jung, Sun Ah; Lee, Seung-Taek; Yun, Cheol Won; Seol, Dai Wu; Kim, Tae Hyoung.

In: Experimental Cell Research, Vol. 312, No. 19, 15.11.2006, p. 3892-3898.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Generation of a novel proform of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein that can be reactivated by matrix metalloproteinases

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

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.

UR - http://www.scopus.com/inward/record.url?scp=33750366469&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750366469&partnerID=8YFLogxK

U2 - 10.1016/j.yexcr.2006.08.015

DO - 10.1016/j.yexcr.2006.08.015

M3 - Article

VL - 312

SP - 3892

EP - 3898

JO - Experimental Cell Research

JF - Experimental Cell Research

SN - 0014-4827

IS - 19

ER -