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

@article{Seo2009TheCD,
  title={The cell death-inducing activity of the peptide containing Noxa mitochondrial-targeting domain is associated with calcium release.},
  author={Young Woo Seo and Ha Na Woo and Sujan Piya and Ae Ran Moon and Jae-Wook Oh and Cheol-Won Yun and Kyung-Keun Kim and Ji-young Min and Seon‐Yong Jeong and Seyung S Chung and Peter I. Song and Seong-Yun Jeong and Eun Kyung Choi and Dai-wu Seol and Tae-Hyoung Kim},
  journal={Cancer research},
  year={2009},
  volume={69 21},
  pages={
          8356-65
        }
}
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… 
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A peptide containing Noxa mitochondrial-targeting domain induces cell death via mitochondrial and endoplasmic reticulum disruption.

Mitochondrial Targeting Domain Homologs Induce Necrotic Cell Death Via Mitochondrial and Endoplasmic Reticulum Disruption

Comparison of peptide sequences showed that four amino acid sites of MTD are critical in regulating necrosis, suggesting the potential to generate artificial, adjustable cytotoxic peptides, which could be effective medicines for many diseases.

Mitochondrial targeted peptides for cancer therapy

Understanding the molecular mechanisms and signaling pathways controlling cell death by MTPs can be critical for the development of the therapeutic strategies for cancer patients that would be valuable for researchers in both fields of molecular and clinical oncology.

MTD-like motif of a BH3-only protein, BNIP1, induces necrosis accompanied by an intracellular calcium spike.

Bcl-2 proteins and mitochondria--specificity in membrane targeting for death.

Designing a cancer therapeutic peptide by combining the mitochondrial targeting domain of Noxa and ErbB2‐targeting moieties

In vivo analysis using a mouse model shows that KWSY:MTD partially suppressed growth in tumor tissue bearing ErbB2‐expressing cells, but did not have obvious toxicity in mouse liver or kidney tissue.

Anti-Tumoral Effect of the Mitochondrial Target Domain of Noxa Delivered by an Engineered Salmonella typhimurium

It is demonstrated that DS4.3-MTD chimeric molecules expressed by the Salmonellae were anti-tumoral in cultured tumor cells and in mice with CT26 colon carcinoma.

Targeted Delivery of the Mitochondrial Target Domain of Noxa to Tumor Tissue via Synthetic Secretion System in E. coli

This work potentiates the use of biotherapeutic bacteria for the treatment of tumors by implanting a dedicated delivery system from a native genetic system encoded in Salmonella pathogenicity island-1 (SPI-1) with no virulence effectors.

Effective modification of cell death-inducing intracellular peptides by means of a photo-cleavable peptide array-based screening system.

Therapeutic implications of novel peptides targeting ER-mitochondria Ca2+-flux systems.

References

SHOWING 1-10 OF 31 REFERENCES

The Molecular Mechanism of Noxa-induced Mitochondrial Dysfunction in p53-Mediated Cell Death*

It is shown that two domains (BH3 domain and mitochondrial targeting domain) in Noxa are essential for the release of cytochrome c from mitochondria, suggesting that there are at least two different pathways of mitochondrial dysfunction.

BOK and NOXA Are Essential Mediators of p53-dependent Apoptosis*

Results indicated that translocation of cytochrome c does not require prior activation of caspases but rather depends on activation of specific BCL-2 family members, depending upon the type of death signal, and proposed a model of the intrinsic apoptotic cascade where proapoptotic BOK substitutes for a function of BAX.

Involvement of Noxa in Cellular Apoptotic Responses to Interferon, Double-stranded RNA, and Virus Infection*

Data suggest that Noxa is an important component of the innate immune response of cells to viral infection, leading to enhanced cellular apoptosis that may play a role in limiting viral dissemination.

Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis.

A previously unidentified pro-apoptotic gene, Noxa, which encodes a Bcl-2 homology 3 (BH3)-only member of the BCl-2 family of proteins may represent a mediator of p53-dependent apoptosis.

Proapoptotic BAX and BAK: A Requisite Gateway to Mitochondrial Dysfunction and Death

Multiple death signals influence mitochondria during apoptosis, yet the critical initiating event for mitochondrial dysfunction in vivo has been unclear. tBID, the caspase-activated form of a…

Functional Dissection of the Pro-apoptotic Protein Bik

The results suggest that for Bik-mediated cell death, the heterodimerization activity encoded by the BH3 domain alone is insufficient and raise the possibility that Bik may induce cell death autonomous of heterodimensionization with survival proteins such as Bcl-2 and BCl-xL.

BCL-2, BCL-X(L) sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis.

BH3 domains of BH3-only proteins differentially regulate Bax-mediated mitochondrial membrane permeabilization both directly and indirectly.

Inhibition of caspase activity induces a switch from apoptosis to necrosis

Structure of the BH3 domains from the p53-inducible BH3-only proteins Noxa and Puma in complex with Mcl-1.