Hop: An Hsp70/Hsp90 Co-Chaperone That Functions Within and Beyond Hsp70/Hsp90 Protein Folding Pathways

Daniel, Sheril; Sőti, Csaba; Csermely, Péter; Bradley, Graeme; Blatch, Gregory L.

doi:10.1007/978-0-387-49310-7_3

Cited by 4 publications

(7 citation statements)

References 78 publications

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“…The best characterized function of Hop protein is its participation in steroid receptor signaling including glucocorticoid response (reviewed in Daniel et al) . More recent findings suggest that Hop can not only associate with Hsp70 and 90 and modulate their activities, but also interact with several other proteins as mentioned above as well as the prion proteins. , There is evidence that murine homologue mSTI and human Hop may be phosphorylated and this modification affects protein localization. , In our study, the Hop in resistant CEM-BOH cells was more acidic than in parental CEM cells sensitive to CDKI bohemine but resistant to glucocorticoid dexamethasone suggesting that in CEM-BOH resistant cells Hop may undergo enhanced phosphorylation. Further findings from immunohistochemistry revealed that Hop is localized in nucleus as well as cytoplasm in CEM-BOH resistant cells in contrast to its prevailing accumulation in nucleus in CEM cells.…”

Section: Discussionsupporting

confidence: 48%

“…36 The best characterized function of Hop protein is its participation in steroid receptor signaling including glucocorticoid response (reviewed in Daniel et al). 37 More recent findings suggest that Hop can not only associate with Hsp70 and 90 and modulate their activities, but also interact with several other proteins as mentioned above as well as the prion proteins. 15,37 There is evidence that murine homologue mSTI and human Hop may be phosphorylated and this modification affects protein localization.…”

Section: Discussionmentioning

confidence: 94%

“…37 More recent findings suggest that Hop can not only associate with Hsp70 and 90 and modulate their activities, but also interact with several other proteins as mentioned above as well as the prion proteins. 15,37 There is evidence that murine homologue mSTI and human Hop may be phosphorylated and this modification affects protein localization. 14,38 In our study, the Hop in resistant CEM-BOH cells was more acidic than in parental CEM cells sensitive to CDKI bohemine but resistant to glucocorticoid dexamethasone suggesting that in CEM-BOH resistant cells Hop may undergo enhanced phosphorylation.…”

Section: Discussionmentioning

confidence: 94%

See 2 more Smart Citations

Cancer Drug-Resistance and a Look at Specific Proteins: Rho GDP-Dissociation Inhibitor 2, Y-Box Binding Protein 1, and HSP70/90 Organizing Protein in Proteomics Clinical Application

et al. 2010

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Resistance to anti-cancer drugs is a well recognized problem and very often it is responsible for failure of the cancer treatment. In this study, the proteome alterations associated with the development of acquired resistance to cyclin-depedent kinases inhibitor bohemine, a promising anti-cancer drug, were analyzed with the primary aim of identifying potential targets of resistance within the cell that could pave a way to selective elimination of specific resistant cell types. A model of parental susceptible CEM T-lymphoblastic leukemia cells and its resistant counterpart CEM-BOH was used and advanced 2-D liquid chromatography was applied to fractionate cellular proteins. Differentially expressed identified proteins were further verified using immunoblotting and immunohistochemistry. Our study has revealed that Rho GDP-dissociation inhibitor 2, Y-box binding protein 1, and the HSP70/90 organizing protein have a critical role to play in resistance to cyclin-depedent kinases inhibitor. The results indicated not only that quantitative protein changes play an important role in drug-resistance, but also that there are various other parameters such as truncation, post-translational modification(s), and subcellular localization of selected proteins. Furthermore, these proteins were validated for their roles in drug resistance using different cell lines resistant to diverse representatives of anti-cancer drugs such as vincristine and daunorubicin.

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Section: Discussionsupporting

confidence: 48%

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 94%

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Cancer Drug-Resistance and a Look at Specific Proteins: Rho GDP-Dissociation Inhibitor 2, Y-Box Binding Protein 1, and HSP70/90 Organizing Protein in Proteomics Clinical Application

et al. 2010

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“…The Hsp70 chaperones need JDPs to provide client specificity and activate their ATPase activity. Additionally, co-chaperones such as the TPR-containing Hsc70-Hsp90 organizing protein Hop bridge the activity of Hsp70, which functions on more nascent polypeptide clients, with Hsp90, which folds clients that are closer to their native conformation 32 . Like Hop, DnaJC7 bridges Hsp70 and Hsp90.…”

Section: Dnajc7 Cooperates With Hsp70 To Regulate Intracellular Tau A...mentioning

confidence: 99%

DnaJC7 specifically regulates tau seeding

Pérez

Sanders

Mendoza-Oliva

et al. 2023

Preprint

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Neurodegenerative tauopathies are caused by accumulation of toxic tau protein assemblies. This appears to involve template-based seeding events, whereby tau monomer changes conformation and is recruited to a growing aggregate. Several large families of chaperone proteins, including Hsp70s and J domain proteins (JDPs) cooperate to regulate the folding of intracellular proteins such as tau, but the factors that coordinate this activity are not well known. The JDP DnaJC7 binds tau and reduces its intracellular aggregation. However, it is unknown whether this is specific to DnaJC7 or if other JDPs might be similarly involved. We used proteomics within a cell model to determine that DnaJC7 co-purified with insoluble tau and colocalized with intracellular aggregates. We individually knocked out every possible JDP and tested the effect on intracellular aggregation and seeding. DnaJC7 knockout decreased aggregate clearance and increased intracellular tau seeding. This depended on the ability of the J domain (JD) of DnaJC7 to bind to Hsp70, as JD mutations that block binding to Hsp70 abrogated the protective activity. Disease-associated mutations in the JD and substrate binding site of DnaJC7 also abrogated its protective activity. DnaJC7 thus specifically regulates tau aggregation in cooperation with Hsp70.

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“…TPR co-chaperones do not directly bind non-native proteins, but have an integral role in directing the activity of HSP90, for example HOP serves as an adaptor and facilitates the shuttling of non-native substrates from HSP70 to HSP90 [30]. The N-terminal TPR domain (TPR1) of HOP is responsible for interaction with the C-terminus of HSP70, whereas the C-terminal TPR domain (TPR2) facilitates interaction with HSP90 [31].…”

Section: Hsp90mentioning

confidence: 99%

The Chemical Biology of Molecular Chaperones—Implications for Modulation of Proteostasis

Brandvold

Morimoto

2015

Journal of Molecular Biology

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Protein homeostasis (proteostasis) is inextricably tied to cellular health and organismal lifespan. Aging, exposure to physiological and environmental stress, and expression of mutant and metastable proteins can cause an imbalance in the protein folding landscape, resulting in the formation of non-native protein aggregates that challenge the capacity of the proteostasis network (PN), increasing the risk for diseases associated with misfolding, aggregation and aberrant regulation of cell stress responses. Molecular chaperones have central roles in each of the arms of the PN (protein synthesis, folding, disaggregation, and degradation), leading to the proposal that modulation of chaperone function could have therapeutic benefits for the large and growing family of diseases of protein conformation including neurodegeneration, metabolic diseases, and cancer. In this review, we will discuss the current strategies used to tune the PN through targeting molecular chaperones and assess the potential of the chemical biology of proteostasis.

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Hop: An Hsp70/Hsp90 Co-Chaperone That Functions Within and Beyond Hsp70/Hsp90 Protein Folding Pathways

Cited by 4 publications

References 78 publications

Cancer Drug-Resistance and a Look at Specific Proteins: Rho GDP-Dissociation Inhibitor 2, Y-Box Binding Protein 1, and HSP70/90 Organizing Protein in Proteomics Clinical Application

Cancer Drug-Resistance and a Look at Specific Proteins: Rho GDP-Dissociation Inhibitor 2, Y-Box Binding Protein 1, and HSP70/90 Organizing Protein in Proteomics Clinical Application

DnaJC7 specifically regulates tau seeding

The Chemical Biology of Molecular Chaperones—Implications for Modulation of Proteostasis

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