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Minimal killing unit of the mitochondrial targeting domain of Noxa
Author(s) -
Kim JiYoung,
Han Ji Hye,
Moon AeRan,
Park Jung Hee,
Chang Jeong Hwan,
Bae Jeehyeon,
Kim TaeHyoung
Publication year - 2013
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.2525
Subject(s) - hela , mitochondrion , in vivo , in vitro , programmed cell death , cancer research , biology , cell , apoptosis , microbiology and biotechnology , chemistry , biochemistry , genetics
Noxa is a key player in p53‐induced cell death via mitochondrial dysfunction, and the mitochondrial‐targeting domain (MTD) of Noxa is responsible for the translocation of Noxa to mitochondria and for the induction of necrotic cell death. The purpose of this study was to define the minimal killing unit of MTD in vitro and in vivo . It was found that the peptides R8:MTD(10), R8:MTD(9), and R8:MTD(8) can kill various human tumor cells (HCT116, HeLa, MCF‐7, BJAB), but that R8:MTD(7) abolishes the killing activity of MTD mainly because of the loss of mitochondrial targeting activity. We find it interesting that R8:MTD(8) was found to kill tumor cells but showed a limited killing activity on normal peritoneal macrophages. Furthermore, R8:MTD(10), R8:MTD(9), and R8:MTD(8) limitedly suppressed tumor growth when injected i.v. into BalB/C mice bearing CT26 cell‐derived tumors. These results indicate that MTD(8) is the minimal killing unit of MTD. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.