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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
이공주이수영강상원김재상이두재
SCOPUS Author ID
이공주scopusscopus; 이수영scopusscopus; 강상원scopus; 김재상scopus; 이두재scopus
Issue Date
2010
Journal Title
PLoS ONE
ISSN
1932-6203JCR Link
Citation
PLoS ONE vol. 5, no. 3
Indexed
SCIE; SCOPUS WOS 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
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