The cell death-inducing activity of the peptide containing noxa mitochondrial-targeting domain is associated with calcium release

Young Woo Seo, Ha Na Woo, Sujan Piya, Ae Ran Moon, Jae Wook Oh, Cheol Won Yun, Kyung Keun Kim, Ji Young Min, Seon Yong Jeong, Seyung Chung, Peter I. Song, Seong Yun Jeong, Eun Kyung Choi, Dai Wu Seol, Tae Hyoung Kim

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

DNA damage stabilizes the p53 tumor suppressor protein that determines the cell fate by either cell cycle arrest or cell death induction. Noxa, the BH3-only Bcl-2family protein, was shown to be a key player in p53-induced cell death through the mitochondrial dysfunction; however, the molecular mechanism by which Noxa induces the mitochondrial dysfunction to cause cell death in response to genotoxic agents is largely unknown. Here, we show that the mitochondrial-targeting domain (MTD) of Noxa is a prodeath domain. Peptide containing MTD causes massive necrosis in vitro through cytosolic calcium increase; it is released from the mitochondria by opening the mitochondrial permeability transition pore. MTD peptide-induced cell death can be inhibited by calcium chelator BAPTA-AM. Moreover, MTD peptide shows the potent tumor-killing activities in mice by joining with tumor-homing motifs.

Original languageEnglish
Pages (from-to)8356-8365
Number of pages10
JournalCancer Research
Volume69
Issue number21
DOIs
Publication statusPublished - 2009 Nov 1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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