Cytosolic Hsp60 Is Involved in the NF-kappa B-Dependent Survival of Cancer Cells via IKK Regulation
- Authors
- Chun, Jung Nyeo; Choi, Boae; Lee, Kyung Wha; Lee, Doo Jae; Kang, Dong Hoon; Lee, Joo Young; Song, In Sung; Kim, Hye In; Lee, Sang-Hee; Kim, Hyeon Soo; Lee, Na Kyung; Lee, Soo Young; Lee, Kong-Joo; Kim, Jaesang; Kang, Sang Won
- Issue Date
- 23-3월-2010
- Publisher
- PUBLIC LIBRARY SCIENCE
- Citation
- PLOS ONE, v.5, no.3
- Indexed
- SCIE
SCOPUS
- Journal Title
- PLOS ONE
- Volume
- 5
- Number
- 3
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/116787
- DOI
- 10.1371/journal.pone.0009422
- ISSN
- 1932-6203
- Abstract
- Cytoplasmic presence of Hsp60, which is principally a nuclear gene-encoded mitochondrial chaperonin, has frequently been stated, but its role in intracellular signaling is largely unknown. In this study, we demonstrate that the cytosolic Hsp60 promotes the TNF-alpha-mediated activation of the IKK/NF-kappa B survival pathway via direct interaction with IKK alpha/beta in the cytoplasm. Selective loss or blockade of cytosolic Hsp60 by specific antisense oligonucleotide or neutralizing antibody diminished the IKK/NF-kappa B activation and the expression of NF-kappa B target genes, such as Bfl-1/A1 and MnSOD, which thus augmented intracellular ROS production and ASK1-dependent cell death, in response to TNF-alpha. Conversely, the ectopic expression of cytosol-targeted Hsp60 enhanced IKK/NF-kappa B activation. Mechanistically, the cytosolic Hsp60 enhanced IKK activation via upregulating the activation-dependent serine phosphorylation in a chaperone-independent manner. Furthermore, transgenic mouse study showed that the cytosolic Hsp60 suppressed hepatic cell death induced by diethylnitrosamine in vivo. The cytosolic Hsp60 is likely to be a regulatory component of IKK complex and it implicates the first mitochondrial factor that regulates cell survival via NF-kappa B pathway.
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Collections - Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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