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

Jin N. Shin, Sun Young Park, Jong Hee Cha, Jae Yoon Park, Byung Rai Lee, Sun A. Jung, Seung Taek Lee, Cheol-Won Yun, Dai W. 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

Keywords

  • Cell death
  • Matrix metalloproteinase
  • TRAIL

ASJC Scopus subject areas

  • Cell Biology

Cite this

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

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

Research output: Contribution to journalArticle

Shin, Jin N. ; Park, Sun Young ; Cha, Jong Hee ; Park, Jae Yoon ; Lee, Byung Rai ; Jung, Sun A. ; Lee, Seung Taek ; Yun, Cheol-Won ; Seol, Dai W. ; 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.
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