Role of hsp90 and the hsp90-binding immunophilins in signalling protein movement

被引:225
作者
Pratt, WB
Galigniana, MD
Harrell, JM
DeFranco, DB
机构
[1] Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA
[2] Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA
关键词
immunophilins; steroid receptors; hsp90; dynein; microtubules; signal protein trafficking;
D O I
10.1016/j.cellsig.2004.02.004
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The ubiquitous protein chaperone hsp90 has been shown to regulate more than 100 proteins involved in cellular signalling. These proteins are called 'client proteins' for hsp90, and a multiprotein hsp90/hsp70-based chaperone machinery forms client protein(.)hsp90 heterocomplexes in the cytoplasm and the nucleus. In the case of signalling proteins that act as transcription factors, the client protein (.) hsp90 complexes also contain one of several TPR domain immunophilins or immunophilin homologs that bind to a TPR domain binding site on hsp90. Using several intracellular receptors and the tumor suppressor p53 as examples, we review evidence that dynamic assembly of heterocomplexes with hsp90 is required for rapid movement through the cytoplasm to the nucleus along microtubular tracks. The role of the immunophilin in this system is to connect the client protein(.)hsp90 complex to cytoplasmic dynein, the motor protein for retrograde movement toward the nucleus. Upon arrival at the nuclear pores, the receptor(.)hsp90(.)immunophilin complexes are transferred to the nuclear interior by importin-dependent facilitated diffusion. The unliganded receptors then distribute within the nucleus to diffuse patches from which they procede in a ligand-dependent manner to discrete nuclear foci where chromatin binding occurs. We review evidence that dynamic assembly of heterocomplexes with hsp90 is required for movement to these foci and for the dynamic exchange of transcription factors between chromatin and the nucleoplasm. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:857 / 872
页数:16
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