American Association for Cancer Research
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00085472can090349-sup-sfig_4.pdf (2.38 MB)

Supplementary Figure 4 from The Cell Death–Inducing Activity of the Peptide Containing Noxa Mitochondrial-Targeting Domain Is Associated with Calcium Release

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posted on 2023-03-30, 19:03 authored by 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
Supplementary Figure 4 from The Cell Death–Inducing Activity of the Peptide Containing Noxa Mitochondrial-Targeting Domain Is Associated with Calcium Release

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ARTICLE 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-2 family 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. [Cancer Res 2009;69(21):8356–65]