Hsp110 Is a Bona Fide Chaperone Using ATP to Unfold Stable Misfolded Polypeptides and Reciprocally Collaborate with Hsp70 to Solubilize Protein Aggregates

Mattoo, Rayees U.H.; Sharma, Sandeep; Priya, Smriti; Finka, Andrija; Goloubinoff, Pierre

doi:10.1074/jbc.m113.479253

Cited by 153 publications

(180 citation statements)

References 60 publications

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“…7C). In accordance with this, we also observed the up-regulation of the chaperone Hsp110 (HSPH1) that has recently been described as part of the cytosolic machinery responsible for the disaggregation of peptide aggregates (55)(56)(57). The other two main elements of the disaggregating complex, Hsp40 (DNAJA1) and Hsp70 (HSPA1A), were also up-regulated in cells incubated with PepL (Fig.…”

Section: Pepl But Not Peps Internalization Requires Hsp70 and Issupporting

confidence: 69%

Sequence-dependent Internalization of Aggregating Peptides

Couceiro

Gallardo

Smet

et al. 2015

Journal of Biological Chemistry

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Background: Prionoid propagation requires cell internalization of aggregated polypeptides. Results: Aggregates of different sequence are internalized through different endocytic pathways. Only phagocytosed aggregates (Ͼ1 m) elicit an HSF1-dependent proteostatic response. Conclusion: Proteostatic response upon aggregate internalization differs markedly depending on the sequence. Significance: The characterization of mechanisms of cell penetration is fundamental for the understanding of aggregate transmission in disease.

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Section: Pepl But Not Peps Internalization Requires Hsp70 and Issupporting

confidence: 69%

Sequence-dependent Internalization of Aggregating Peptides

Couceiro

Gallardo

Smet

et al. 2015

Journal of Biological Chemistry

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“…12 In recent years, HSP110 has become a new point of interest in the field of HSP and cancer, mainly thanks to its excellent chaperoning capacity of peptide antigens, which makes it a powerful tool for vaccine development. 48,49 Until our recently published works demonstrating the essential role of HSP110 in CRC, its role in tumor development remained almost unexplored. This study brings new information to the emerging role of extracellular HSP110 in the inhibition of the immune system in the context of tumor microenvironment.…”

Section: E1170264-6mentioning

confidence: 99%

Extracellular HSP110 skews macrophage polarization in colorectal cancer

et al. 2016

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HSP110 is induced by different stresses and, through its anti-apoptotic and chaperoning properties, helps the cells to survive these adverse situations. In colon cancers, HSP110 is abnormally abundant. We have recently showed that colorectal cancer (CRC) patients with microsatellite instability (MSI) had an improved response to chemotherapy because they harbor an HSP110 inactivating mutation (HSP110DE9). In this work, we have used patients' biopsies and human CRC cells grown in vitro and in vivo (xenografts) to demonstrate that (1) HSP110 is secreted by CRC cells and that the amount of this extracellular HSP110 is strongly decreased by the expression of the mutant HSP110DE9, (2) Supernatants from CRC cells overexpressing HSP110 or purified recombinant human HSP110 (LPS-free) affect macrophage differentiation/polarization by favoring a pro-tumor, anti-inflammatory profile, (3) Conversely, inhibition of HSP110 (expression of siRNA, HSP110DE9 or immunodepletion) induced the formation of macrophages with a cytotoxic, pro-inflammatory profile. (4) Finally, this effect of extracellular HSP110 on macrophages seems to implicate TLR4. These results together with the fact that colorectal tumor biopsies with HSP110 high were infiltrated with macrophages with a pro-tumoral profile while those with HSP110 low were infiltrated with macrophages with a cytotoxic profile, suggest that the effect of extracellular HSP110 function on macrophages may also contribute to the poor outcomes associated with HSP110 expression.

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“…However, Hsp105 had the intrinsic ability to bind ATP-FAM and hydrolyze ATP (Fig. 6D) (80), so its ability to promote nucleotide release could not be reliably tested. Finally, when we combined Hsp105 with Hsp72 and the four J proteins, we found that it was unable to significantly promote nucleotide hydrolysis of any of the Hsp72 combinations ( Fig.…”

Section: Hsp105 Competes With Bag Proteins and Acts As A Nef-mentioning

confidence: 99%

Binding of Human Nucleotide Exchange Factors to Heat Shock Protein 70 (Hsp70) Generates Functionally Distinct Complexes in Vitro

Rauch

Gestwicki

2014

Journal of Biological Chemistry

140

171

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Background: There has been an expansion of the number of Hsp70 cochaperones in mammals, providing the opportunity for combinatorial assembly of permutations with specialized functions. Results: We studied the chaperone activity of Hsp70 combined with four different NEFs and four J proteins. Conclusion: Some combinations were active, whereas others were inactive. Significance: Cochaperones appear to expand the functional diversity of Hsp70.

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Hsp110 Is a Bona Fide Chaperone Using ATP to Unfold Stable Misfolded Polypeptides and Reciprocally Collaborate with Hsp70 to Solubilize Protein Aggregates

Cited by 153 publications

References 60 publications

Sequence-dependent Internalization of Aggregating Peptides

Sequence-dependent Internalization of Aggregating Peptides

Extracellular HSP110 skews macrophage polarization in colorectal cancer

Binding of Human Nucleotide Exchange Factors to Heat Shock Protein 70 (Hsp70) Generates Functionally Distinct Complexes in Vitro

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