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http://dx.doi.org/10.5483/BMBRep.2016.49.5.245

Potentiation of TRAIL killing activity by multimerization through isoleucine zipper hexamerization motif  

Han, Ji Hye (Departments of Biochemistry, Chosun University School of Medicine)
Moon, Ae Ran (Departments of Biochemistry, Chosun University School of Medicine)
Chang, Jeong Hwan (Departments of Surgery, Chosun University School of Medicine)
Bae, Jeehyeon (School of Pharmacy, Chung-Ang University)
Choi, Jin Myung (Departments of Cellular and Molecular Medicine, Chosun University School of Medicine)
Lee, Sung Haeng (Departments of Cellular and Molecular Medicine, Chosun University School of Medicine)
Kim, Tae-Hyoung (Departments of Biochemistry, Chosun University School of Medicine)
Publication Information
BMB Reports / v.49, no.5, 2016 , pp. 282-287 More about this Journal
Abstract
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.
Keywords
Apoptosis; Cell death; Isoleucine zipper; Multimerization; TRAIL;
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