期刊
BMB REPORTS
卷 49, 期 5, 页码 282-287出版社
KOREAN SOCIETY BIOCHEMISTRY & MOLECULAR BIOLOGY
DOI: 10.5483/BMBRep.2016.49.5.245
关键词
Apoptosis; Cell death; Isoleucine zipper; Multimerization; TRAIL
资金
- Basic Science Research Program through the National Research Foundation of Korea - the Ministry of Education, Science and Technology [2010-0009201, NRF-2013R1A1A2058254]
- Ministry of Science, ICT, and Future Planning [NRF-2014R1A2A1A11050442]
- National R & D Program for Cancer Control - the Ministry of Health and Welfare of the Korean government [1020100]
- Clinical Medicine Research Institute at Chosun University Hospital [Y2011]
- Korea Health Promotion Institute [1020100] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2010-0009201] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a homo-trimeric cytotoxic ligand. Several studies have demonstrated that incorporation of artificial trimerization motifs into the TRAIL protein leads to the enhancement of biological activity. Here, we show that linkage of the isoleucine zipper hexamerization motif to the N-terminus of TRAIL, referred as ILz(6): TRAIL, leads to multimerization of its trimeric form, which has higher cytotoxic activity compared to its native state. Size exclusion chromatography of ILz(6): TRAIL revealed possible existence of various forms such as trimeric, hexameric, and multimeric (possibly containing one-, two-, and multi-units of trimeric TRAIL, respectively). Increased number of multimerized ILz(6): TRAIL units corresponded with enhanced cytotoxic activity. Further, a high degree of ILz(6): TRAIL multimerization triggered rapid signaling events such as activation of caspases, tBid generation, and chromatin condensation. Taken together, these results indicate that multimerization of TRAIL significantly enhances its cytotoxic activity.
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