Abstract:
:Heat shock protein 90 (Hsp90) serves to stabilise and correctly fold multiple significant client proteins associated with cell proliferation and cell survival. However, little is known about the Hsp90 client proteins that regulate cell metabolism. Here, we describe a unique ability of Hsp90 to regulate the stability and activity of AMP-activated kinase (AMPK), a key sensor of cellular energy status. Hsp90 is found to interact with AMPK and to maintain its AMP-activated kinase activity, which in turn is required for the phosphorylation of its substrate, acetyl-CoA carboxylase (ACC), the key enzyme in fatty acid metabolism. Our binding analysis reveals that both the γ subunit and the α subunit of AMPK bind to Hsp90 with a high affinity. We demonstrate that Hsp90 inhibitors, including geldanamycin (GA) and mycoepoxydiene (MED), can induce the dissociation of AMPK from Hsp90, and cause a significant decrease in phosphorylation of AMPK and ACC. Furthermore, we demonstrate that shRNAs of Hsp90 can efficiently suppress the activation of AMPK. These findings not only establish a novel interaction between Hsp90 and AMPK but also suggest a new mechanism for regulating tumour cell fatty acid metabolism.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Zhang L,Yi Y,Guo Q,Sun Y,Ma S,Xiao S,Geng J,Zheng Z,Song Sdoi
10.1016/j.cellsig.2011.12.001subject
Has Abstractpub_date
2012-04-01 00:00:00pages
859-65issue
4eissn
0898-6568issn
1873-3913pii
S0898-6568(11)00379-2journal_volume
24pub_type
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