Document Detail

Generation of a novel proform of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein that can be reactivated by matrix metalloproteinases.
MedLine Citation:
PMID:  16996498     Owner:  NLM     Status:  MEDLINE    
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-alpha. Taken together, the data suggested that the sTRAIL:IL-18 can be reactivated at the specialized areas where MMPs are pathologically produced.
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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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-08-25
Journal Detail:
Title:  Experimental cell research     Volume:  312     ISSN:  0014-4827     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-12-05     Completed Date:  2007-01-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3892-8     Citation Subset:  IM    
Department of Biochemistry, Chosun University School of Medicine, 375 Seosuk-Dong, Dong-Gu, Gwangju 501-759, Republic of Korea.
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MeSH Terms
Base Sequence
DNA, Complementary / genetics
Hela Cells
Interleukin-18 / genetics,  metabolism
Matrix Metalloproteinase 2 / metabolism
Matrix Metalloproteinases / metabolism*
Protein Precursors / genetics,  metabolism
Recombinant Fusion Proteins / genetics,  metabolism
TNF-Related Apoptosis-Inducing Ligand / genetics,  metabolism*
Tumor Necrosis Factor-alpha / pharmacology
Reg. No./Substance:
0/DNA, Complementary; 0/Interleukin-18; 0/Protein Precursors; 0/Recombinant Fusion Proteins; 0/TNF-Related Apoptosis-Inducing Ligand; 0/TNFSF10 protein, human; 0/Tumor Necrosis Factor-alpha; EC 3.4.24.-/Matrix Metalloproteinases; EC Metalloproteinase 2

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