Hip, a novel cochaperone involved in the eukaryotic hsc70/hsp40 reaction cycle

Höhfeld, Jörg; Minami, Yoshiko; Hartl, F. Ulrich

doi:10.1016/0092-8674(95)90099-3

Cited by 409 publications

(411 citation statements)

References 34 publications

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“…In rabbit reticulocyte lysate, Hip binds to PR complexes at the intermediate stages of steps 1 and 2 (17). Hip has been shown to bind to hsp70 and to stabilize the ADP-bound state of hsp70 (16). Thus far, we have not observed any influence of Hip on the reconstitution system described here.…”

Section: Resultsmentioning

confidence: 52%

“…Hop (hsp-organizing protein) is a 60-kDa stress-related protein that binds to both hsp70 and hsp90 (9,(13)(14)(15). Hip (hsp70-interacting protein) is also known to bind to hsp70 (16,17). This intermediate complex has been shown in time course studies of PR assembly, and it is the predominant form when the ATP level is suboptimal (6,12) and when further assembly is blocked by the benzoquinone ansamycin, geldanamycin (18,19), which binds to the ATP-binding site on hsp90 and blocks some of its functions (20 -23).…”

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confidence: 99%

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The Assembly of Progesterone Receptor-hsp90 Complexes Using Purified Proteins

Kosano¹,

Stensgard²,

Charlesworth³

et al. 1998

Journal of Biological Chemistry

231

250

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The progesterone receptor can be reconstituted into hsp90-containing complexes in vitro, and the resulting complexes are needed to maintain hormone binding activity. This process requires ATP/Mg 2؉ , K ؉ , and several axillary proteins. We have developed a defined system for the assembly of progesterone receptor complexes using purified proteins. Five proteins are needed to form complexes that are capable of maintaining hormone binding activity. These include hsp70 and its cochaperone, hsp40, the hsp70/hsp90-binding protein, Hop, hsp90, and the hsp90-binding protein, p23. The proteins Hip and FKBP52 were not required for this in vitro process even though they have been observed in receptor complexes. Each of the five proteins showed a characteristic concentration dependence. Similar concentrations of hsp70, hsp90, and p23 were needed for optimal assembly, but hsp40 and Hop were effective at about 1/10 the concentration of the other proteins, suggesting that these two proteins act catalytically or are needed at levels similar to the receptor concentration. ATP was required for the functioning of both hsp70 and hsp90. The binding of hsp70 to the receptor requires hsp40 and about 10 M ATP; however, hsp90 binding appears to occur subsequent to hsp70 binding and is optimal with 1 mM ATP. A three-step model is presented to describe the assembly process.When extracted from tissue cytosol, receptors for progesterone (PR), 1 glucocorticoid (GR), and other steroids exist in heteromeric complexes containing heat shock protein 90 (hsp90) and several additional proteins (1-3). Recent information on the assembly of these complexes has been gained mainly through the use of an in vitro system consisting of immuneisolated progesterone (4) or glucocorticoid (5) receptor incubated in rabbit reticulocyte lysate. The formation of receptor complexes in this system is dependent upon ATP hydrolysis, the ions Mg 2ϩ and K ϩ , and the participation of a number of proteins (6, 7). When assembled in vitro, the mature avian progesterone receptor complex closely resembles that obtained from oviduct cytosol and contains hsp90, any one of three immunophilins, and a 23-kDa phosphoprotein, p23. It also contains variable sub-stoichiometric amounts of hsp70. The immunophilins include the cyclosporin A-binding protein, CyP-40, and two FK506-binding proteins, FKBP51 and FKBP52. Antibody inhibitor studies or depletion and reconstitution experiments indicate that hsp70 (6, 8), Hop, an intermediate in complex assembly (9), and p23 (10, 11) are essential for the formation of hsp90 complexes, but the actual roles of these and other proteins are still unclear.An intermediate in PR complex formation has been identified that contains submaximal amounts of hsp90, substantially more hsp70 than in the mature complex, and two additional proteins, Hop (p60) and Hip (p48) (6, 12). This complex does not contain immunophilins or p23. Hop (hsp-organizing protein) is a 60-kDa stress-related protein that binds to both hsp70 and hsp90 (9, 13-15). Hip (hsp70-interacting ...

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Section: Resultsmentioning

confidence: 52%

mentioning

confidence: 99%

The Assembly of Progesterone Receptor-hsp90 Complexes Using Purified Proteins

Kosano¹,

Stensgard²,

Charlesworth³

et al. 1998

Journal of Biological Chemistry

231

250

View full text Add to dashboard Cite

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“…HIP, Hsp70 Interacting Protein, is a ~ 48 kDa eukaryotic protein that was identified in a yeast two-hybrid screen (Hohfeld et al, 1995). HIP has been shown to interact with the ATPase domain of Hsp70 by its tetratricopeptide repeat (TPR) region (Velten et al, 2000) and this interaction slows dissociation of ADP from Hsp70.…”

Section: Ii41121 the Hsp70 Chaperone Systemmentioning

confidence: 99%

“…HIP has been shown to interact with the ATPase domain of Hsp70 by its tetratricopeptide repeat (TPR) region (Velten et al, 2000) and this interaction slows dissociation of ADP from Hsp70. This stimulates the chaperone activity of Hsp70, presumably because it stabilizes the Hsp70 substrate complex by preventing premature substrate release (Hohfeld et al, 1995). In this regard, HIP is antagonist to BAG-1 which promotes the release of the bound ADP from Hsp70 and results in substrate release (Hohfeld and Jentsch, 1997;Takayama et al, 1997).…”

Section: Ii41121 the Hsp70 Chaperone Systemmentioning

confidence: 99%

Firefly luciferase mutants as sensors of proteome stress

et al. 2011

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“…It is somewhat surprising that the role of GrpE like molecules may not be required for the proper functioning of Hsp70 homologues in other compartments whilst recognisable homologues of DnaJ have been found in the cytosol, mitochondria and endoplasmic reticulum of yeast and mammalian cells (reviewed in [1]). Recently a novel rat cytosolic protein with molecular chaperone activity termed HiP was found to stabilise a labile interaction of cytosolic Hsp70, in the ADP-bound state, with Hsp40 and unfolded polypeptides [24]. This protein bears no obvious sequence relationship to GrpE and appears not to be functionally equivalent.…”

Section: Mt-grpe and A Low Abundance Mitochondrial Protein Of Ubiquitoumentioning

confidence: 99%

Isolation and characterisation of a cDNA encoding rat mitochondrial GrpE, a stress‐inducible nucleotide‐exchange factor of ubiquitous appearance in mammalian organs

1996

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In contrast to the E. coli chaperones DnaK, GroEL and GroES, cDNAs encoding mitochondrial homologues of DnaJ and GrpE from higher eukaryotes have yet to be reported. Based on peptide sequences, we have isolated a cDNA encoding a 217 residue nuclear encoded precursor of rat mitochondrial GrpE (mt-GrpE) including a typical mitochondrial presequence of 27 residues. Western blotting revealed that the 21 kDa GrpE homologue is present exclusively in the mitochondrial fraction where it comprises only ~ 0.03% of the total soluble protein, while Northern blotting showed that the mt-GrpE transcript is present in most if not all organs. By contrast to other mitochondrial chaperones, the levels of mt-GrpE and its transcript in cultured cells are only marginally increased in response to the proline analog L-azetidine 2-carboxylic acid but not by heat shock. Furthermore, members of the GrpE family exhibit a much lower degree of sequence identity than do the well studied members of the Hsp70, Hsp60 and Hspl0 families.

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Hip, a novel cochaperone involved in the eukaryotic hsc70/hsp40 reaction cycle

Cited by 409 publications

References 34 publications

The Assembly of Progesterone Receptor-hsp90 Complexes Using Purified Proteins

The Assembly of Progesterone Receptor-hsp90 Complexes Using Purified Proteins

Firefly luciferase mutants as sensors of proteome stress

Isolation and characterisation of a cDNA encoding rat mitochondrial GrpE, a stress‐inducible nucleotide‐exchange factor of ubiquitous appearance in mammalian organs

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