View : 1026 Download: 278
Cytosolic Hsp60 Is Involved in the NF-kB-Dependent Survival of Cancer Cells via IKK Regulation
- Title
- Cytosolic Hsp60 Is Involved in the NF-kB-Dependent Survival of Cancer Cells via IKK Regulation
- Authors
- Chun J.N.; Choi B.; Lee K.W.; Lee D.J.; Kang D.H.; Lee J.Y.; Song I.S.; Kim H.I.; Lee S.-H.; Kim H.S.; Lee N.K.; Lee S.Y.; Lee K.-J.; Kim J.; Kang S.W.
- Ewha Authors
- 이공주; 이수영; 강상원; 김재상; 이두재
- SCOPUS Author ID
- 이공주; 이수영; 강상원; 김재상; 이두재
- Issue Date
- 2010
- Journal Title
- PLoS ONE
- ISSN
- 1932-6203
- Citation
- PLoS ONE vol. 5, no. 3
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- 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-α-mediated activation of the IKK/NF-kB survival pathway via direct interaction with IKKa/b in the cytoplasm. Selective loss or blockade of cytosolic Hsp60 by specific antisense oligonucleotide or neutralizing antibody diminished the IKK/NF-kB activation and the expression of NF-kB target genes, such as Bfl-1/A1 and MnSOD, which thus augmented intracellular ROS production and ASK1-dependent cell death, in response to TNF-α. Conversely, the ectopic expression of cytosol-targeted Hsp60 enhanced IKK/NF-kB 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-kB pathway. © 2010 Chun et al.
- DOI
- 10.1371/journal.pone.0009422
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
- Files in This Item:
-
Cytosolic Hsp60 Is Involved in the NF-kB-Dependent Survival of Cancer Cells via IKK Regulation.PDF(2.19 MB)
Download
- Export
- RIS (EndNote)
- XLS (Excel)
- XML