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

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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
Issue number19
Publication statusPublished - 2006 Nov 15


All Science Journal Classification (ASJC) codes

  • Cell Biology

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