%0 Journal Article
%T Cytosolic Hsp60 Is Involved in the NF-百B-Dependent Survival of Cancer Cells via IKK Regulation
%A Jung Nyeo Chun
%A Boae Choi
%A Kyung Wha Lee
%A Doo Jae Lee
%A Dong Hoon Kang
%A Joo Young Lee
%A In Sung Song
%A Hye In Kim
%A Sang-Hee Lee
%A Hyeon Soo Kim
%A Na Kyung Lee
%A Soo Young Lee
%A Kong-Joo Lee
%A Jaesang Kim
%A Sang Won Kang
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0009422
%X 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-汐-mediated activation of the IKK/NF-百B survival pathway via direct interaction with IKK汐/汕 in the cytoplasm. Selective loss or blockade of cytosolic Hsp60 by specific antisense oligonucleotide or neutralizing antibody diminished the IKK/NF-百B activation and the expression of NF-百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-汐. Conversely, the ectopic expression of cytosol-targeted Hsp60 enhanced IKK/NF-百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-百B pathway.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0009422