Supplementary Figure 3 from The Cell Death–Inducing Activity of the Peptide Containing Noxa Mitochondrial-Targeting Domain Is Associated with Calcium Release

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

doi:10.1158/0008-5472.22380065.v1

00085472can090349-sup-sfig_3.pdf (21.11 MB)

Supplementary Figure 3 from The Cell Death–Inducing Activity of the Peptide Containing Noxa Mitochondrial-Targeting Domain Is Associated with Calcium Release

journal contribution

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

History

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]