Nuclear translocation of the phosphoprotein Hop (Hsp70/Hsp90 organizing protein) occurs under heat shock, and its proposed nuclear localization signal is involved in Hsp90 binding

Daniel, S. and Bradley, G. and Longshaw, V.M. and Söti, C. and Csermely, P. and Blatch, G.L. (2008) Nuclear translocation of the phosphoprotein Hop (Hsp70/Hsp90 organizing protein) occurs under heat shock, and its proposed nuclear localization signal is involved in Hsp90 binding. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1783 (6). pp. 1003-1014. ISSN 0167-4889

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Official URL: http://dx.doi.org/10.1016/j.bbamcr.2008.01.014

Abstract

The Hsp70–Hsp90 complex is implicated in the folding and regulation of numerous signaling proteins, and Hop, the Hsp70–Hsp90 Organizing Protein, facilitates the association of this multichaperone machinery. Phosphatase treatment of mouse cell extracts reduced the number of Hop isoforms compared to untreated extracts, providing the first direct evidence that Hop was phosphorylated in vivo. Furthermore, surface plasmon resonance (SPR) spectroscopy showed that a cdc2 kinase phosphorylation mimic of Hop had reduced affinity for Hsp90 binding. Hop was predominantly cytoplasmic, but translocated to the nucleus in response to heat shock. A putative bipartite nuclear localization signal (NLS) has been identified within the Hsp90-binding domain of Hop. Although substitution of residues within the major arm of this proposed NLS abolished Hop–Hsp90 interaction as determined by SPR, this was not sufficient to prevent the nuclear accumulation of Hop under leptomycin-B treatment and heat shock conditions. These results showed for the first time that the subcellular localization of Hop was stress regulated and that the major arm of the putative NLS was not directly important for nuclear translocation but was critical for Hop–Hsp90 association in vitro. We propose a model in which the association of Hop with Hsp90 and the phosphorylated status of Hop both play a role in the mechanism of nucleo-cytoplasmic shuttling of Hop.

Item Type:Article
Uncontrolled Keywords:Hop; Heat shock protein; Phosphorylation; Hsp90; Co-chaperone; Nuclear localization signal
Subjects:Y Unknown > Subjects to be assigned
Divisions:Faculty > Faculty of Science > Biochemistry, Microbiology & Biotechnology
ID Code:1011
Deposited By: Mrs Eileen Shepherd
Deposited On:10 Jun 2008
Last Modified:06 Jan 2012 16:19
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