| 1. |
- Brackley, Karen I., 1982, et al.
(författare)
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Activities of the chaperonin containing TCP-1 (CCT): implications for cell cycle progression and cytoskeletal organisation.
- 2009
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Ingår i: Cell Stress and Chaperones. - : Springer Science and Business Media LLC. - 1355-8145 .- 1466-1268. ; 14:1, s. 23-31
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Forskningsöversikt (refereegranskat)abstract
- The chaperonin containing TCP-1 (CCT) is required for the production of native actin and tubulin and numerous other proteins, several of which are involved in cell cycle progression. The mechanistic details of how CCT acts upon its folding substrates are intriguing: whilst actin and tubulin bind in a sequence-specific manner, it is possible that some proteins could use CCT as a more general binding interface. Therefore, how CCT accommodates the folding requirements of its substrates, some of which are produced in a cell cycle-specific manner, is of great interest. The reliance of folding substrates upon CCT for the adoption of their native structures results in CCT activity having far-reaching implications for a vast array of cellular processes. For example, the dependency of the major cytoskeletal proteins actin and tubulin upon CCT results in CCT activity being linked to any cellular process that depends on the integrity of the microfilament and microtubule-based cytoskeletal systems.
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| 2. |
- Carra, Serena, et al.
(författare)
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The growing world of small heat shock proteins : from structure to functions
- 2017
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Ingår i: Cell Stress and Chaperones. - : Springer Science and Business Media LLC. - 1355-8145 .- 1466-1268. ; 22:4, s. 601-611
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Tidskriftsartikel (refereegranskat)abstract
- Small heat shock proteins (sHSPs) are present in all kingdoms of life and play fundamental roles in cell biology. sHSPs are key components of the cellular protein quality control system, acting as the first line of defense against conditions that affect protein homeostasis and proteome stability, from bacteria to plants to humans. sHSPs have the ability to bind to a large subset of substrates and to maintain them in a state competent for refolding or clearance with the assistance of the HSP70 machinery. sHSPs participate in a number of biological processes, from the cell cycle, to cell differentiation, from adaptation to stressful conditions, to apoptosis, and, even, to the transformation of a cell into a malignant state. As a consequence, sHSP malfunction has been implicated in abnormal placental development and preterm deliveries, in the prognosis of several types of cancer, and in the development of neurological diseases. Moreover, mutations in the genes encoding several mammalian sHSPs result in neurological, muscular, or cardiac age-related diseases in humans. Loss of protein homeostasis due to protein aggregation is typical of many age-related neurodegenerative and neuromuscular diseases. In light of the role of sHSPs in the clearance of un/misfolded aggregation-prone substrates, pharmacological modulation of sHSP expression or function and rescue of defective sHSPs represent possible routes to alleviate or cure protein conformation diseases. Here, we report the latest news and views on sHSPs discussed by many of the world’s experts in the sHSP field during a dedicated workshop organized in Italy (Bertinoro, CEUB, October 12–15, 2016).
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| 3. |
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| 4. |
- Kampinga, Harm H., et al.
(författare)
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Function, evolution, and structure of J-domain proteins
- 2019
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Ingår i: Cell stress & chaperones (Print). - : Springer Science and Business Media LLC. - 1355-8145 .- 1466-1268. ; 24:1, s. 7-15
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Forskningsöversikt (refereegranskat)abstract
- Hsp70 chaperone systems are very versatile machines present in nearly all living organisms and in nearly all intracellular compartments. They function in many fundamental processes through their facilitation of protein (re)folding, trafficking, remodeling, disaggregation, and degradation. Hsp70 machines are regulated by co-chaperones. J-domain containing proteins (JDPs) are the largest family of Hsp70 co-chaperones and play a determining role functionally specifying and directing Hsp70 functions. Many features of JDPs are not understood; however, a number of JDP experts gathered at a recent CSSI-sponsored workshop in Gdansk (Poland) to discuss various aspects of J-domain protein function, evolution, and structure. In this report, we present the main findings and the consensus reached to help direct future developments in the field of Hsp70 research.
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| 5. |
- Lambert, Wietske, et al.
(författare)
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Probing the transient interaction between the small heat-shock protein Hsp21 and a model substrate protein using crosslinking mass spectrometry.
- 2012
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Ingår i: Cell Stress & Chaperones. - : Springer Science and Business Media LLC. - 1466-1268 .- 1355-8145.
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Tidskriftsartikel (refereegranskat)abstract
- Small heat-shock protein chaperones are important players in the protein quality control system of the cell, because they can immediately respond to partially unfolded proteins, thereby protecting the cell from harmful aggregates. The small heat-shock proteins can form large polydisperse oligomers that are exceptionally dynamic, which is implicated in their function of protecting substrate proteins from aggregation. Yet the mechanism of substrate recognition remains poorly understood, and little is known about what parts of the small heat-shock proteins interact with substrates and what parts of a partially unfolded substrate protein interact with the small heat-shock proteins. The transient nature of the interactions that prevent substrate aggregation rationalize probing this interaction by crosslinking mass spectrometry. Here, we used a workflow with lysine-specific crosslinking and offline nano-liquid chromatography matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry to explore the interaction between the plant small heat-shock protein Hsp21 and a thermosensitive model substrate protein, malate dehydrogenase. The identified crosslinks point at an interaction between the disordered N-terminal region of Hsp21 and the C-terminal presumably unfolding part of the substrate protein.
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| 6. |
- Marklund, Erik G., Teknologie doktor, 1979-, et al.
(författare)
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Structural and functional aspects of the interaction partners of the small heat-shock protein in Synechocystis
- 2018
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Ingår i: Cell stress & chaperones (Print). - : Springer Science and Business Media LLC. - 1355-8145 .- 1466-1268. ; 23:4, s. 723-732
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Tidskriftsartikel (refereegranskat)abstract
- The canonical function of small heat-shock proteins (sHSPs) is to interact with proteins destabilized under conditions of cellular stress. While the breadth of interactions made by many sHSPs is well-known, there is currently little knowledge about what structural features of the interactors form the basis for their recognition. Here, we have identified 83 in vivo interactors of the sole sHSP in the cyanobacterium Synechocystis sp. PCC 6803, HSP16.6, reflective of stable associations with soluble proteins made under heat-shock conditions. By performing bioinformatic analyses on these interactors, we identify primary and secondary structural elements that are enriched relative to expectations from the cyanobacterial genome. In addition, by examining the Synechocystis interactors and comparing them with those identified to bind sHSPs in other prokaryotes, we show that sHSPs associate with specific proteins and biological processes. Our data are therefore consistent with a picture of sHSPs being broadly specific molecular chaperones that act to protect multiple cellular pathways.
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| 7. |
- Månsson, Cecilia, et al.
(författare)
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DNAJB6 is a peptide-binding chaperone which can suppress amyloid fibrillation of polyglutamine peptides at substoichiometric molar ratios.
- 2014
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Ingår i: Cell Stress & Chaperones. - : Springer Science and Business Media LLC. - 1466-1268 .- 1355-8145. ; 19:2, s. 227-239
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Tidskriftsartikel (refereegranskat)abstract
- Expanded polyglutamine (polyQ) stretches lead to protein aggregation and severe neurodegenerative diseases. A highly efficient suppressor of polyQ aggregation was identified, the DNAJB6, when molecular chaperones from the HSPH, HSPA, and DNAJ families were screened for huntingtin exon 1 aggregation in cells (Hageman et al. in Mol Cell 37(3):355-369, 2010). Furthermore, also aggregation of polyQ peptides expressed in cells was recently found to be efficiently suppressed by co-expression of DNAJB6 (Gillis et al. in J Biol Chem 288:17225-17237, 2013). These suppression effects can be due to an indirect effect of DNAJB6 on other cellular components or to a direct interaction between DNAJB6 and polyQ peptides that may depend on other cellular components. Here, we have purified the DNAJB6 protein to investigate the suppression mechanism. The purified DNAJB6 protein formed large heterogeneous oligomers, in contrast to the more canonical family member DNAJB1 which is dimeric. Purified DNAJB6 protein, at substoichiometric molar ratios, efficiently suppressed fibrillation of polyQ peptides with 45°Q in a thioflavin T fibrillation. No suppression was obtained with DNAJB1, but with the closest homologue to DNAJB6, DNAJB8. The suppression effect was independent of HSPA1 and ATP. These data, based on purified proteins and controlled fibrillation in vitro, strongly suggest that the fibrillation suppression is due to a direct protein-protein interaction between the polyQ peptides and DNAJB6 and that the DNAJB6 has unique fibrillation suppression properties lacking in DNAJB1. Together, the data obtained in cells and in vitro support the view that DNAJB6 is a peptide-binding chaperone that can interact with polyQ peptides that are incompletely degraded by and released from the proteasome.
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| 8. |
- Svanström, Andreas, et al.
(författare)
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The molecular chaperone CCT modulates the activity of the actin filament severing and capping protein gelsolin in vitro
- 2016
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Ingår i: Cell Stress & Chaperones. - : Springer Science and Business Media LLC. - 1355-8145 .- 1466-1268. ; 21:1, s. 55-62
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Tidskriftsartikel (refereegranskat)abstract
- The oligomeric molecular chaperone CCT is essential for the folding of the highly abundant protein actin, which in its native state forms actin filaments that generate the traction forces required for cell motility. In addition to folding proteins, CCT can provide a platform for protein complex assembly and binds actin filaments assembled in vitro. Some individual subunits of CCT, when monomeric, have been shown to be functionally active, and in particular, the CCTepsilon subunit is involved in the serum response factor pathway that controls actin transcription. Thus, there is a complex interplay between CCT and actin that extends beyond actin folding. CCT has recently been shown to bind gelsolin, an actin filament severing protein that increases actin dynamics by generating filament ends for further actin polymerization. However, the biological significance of the CCT:gelsolin interaction is unknown. Here, using a co-immunoprecipitation assay, we show that CCT binds directly to gelsolin in its calcium-activated, actin-severing conformation. Furthermore, using actin filaments retained from fixed and permeabilized cells, we demonstrate that CCT can inhibit the actin filament severing activity of gelsolin. As our work and that of others shows gelsolin is not folded by CCT, the CCT:gelsolin interaction represents a novel mode of binding where CCT may modulate protein activity. The data presented here reveal an additional level of interplay between CCT and actin mediated via gelsolin, suggesting that CCT may influence processes depending on gelsolin activity, such as cell motility.
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| 9. |
- Vallin, Josefine, 1987, et al.
(författare)
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Functional assessment of the V390F mutation in the CCT delta subunit of chaperonin containing tailless complex polypeptide 1
- 2021
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Ingår i: Cell Stress & Chaperones. - : Springer Science and Business Media LLC. - 1355-8145 .- 1466-1268. ; 26, s. 955-964
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Tidskriftsartikel (refereegranskat)abstract
- The chaperonin containing tailless complex polypeptide 1 (CCT) is a multi-subunit molecular chaperone. It is found in the cytoplasm of all eukaryotic cells, where the oligomeric form plays an essential role in the folding of predominantly the cytoskeletal proteins actin and tubulin. Both the CCT oligomer and monomeric subunits also display functions that extend beyond folding, which are often associated with microtubules and actin filaments. Here, we assess the functional significance of the CCT delta V390F mutation, reported in several cancer cell lines. Upon transfection into B16F1 mouse melanoma cells, GFP-CCT delta(V390F) incorporates into the CCT oligomer more readily than GFP-CCT delta. Furthermore, unlike GFP-CCT delta, GFP-CCT delta(V390F) does not interact with the dynactin complex component, p150(Glued). As CCT delta has previously been implicated in altered migration in wound healing assays, we assessed the behaviour of GFP-CCT delta(V390F) and other mutants of CCT delta, previously used to assess functional interactions with p150(Glued), in chemotaxis assays. We developed the assay system to incorporate a layer of the inert hydrogel GrowDex (R) to provide a 3D matrix for chemotaxis assessment and found subtle differences in the migration of B16F1 cells, depending on the presence of the hydrogel.
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| 10. |
- Vallin, Josefine, 1987, et al.
(författare)
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The role of the molecular chaperone CCT in protein folding and mediation of cytoskeleton-associated processes: implications for cancer cell biology.
- 2019
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Ingår i: Cell stress & chaperones. - : Springer Science and Business Media LLC. - 1466-1268 .- 1355-8145. ; 24:1, s. 17-27
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Forskningsöversikt (refereegranskat)abstract
- The chaperonin-containing tailless complex polypeptide 1 (CCT) is required in vivo for the folding of newly synthesized tubulin and actin proteins and is thus intrinsically connected to all cellular processes that rely on the microtubule and actin filament components of the cytoskeleton, both of which are highly regulated and dynamic assemblies. In addition to CCT acting as a protein folding oligomer, further modes of CCT action mediated either by the CCT oligomer itself or via CCT subunits in their monomeric forms can influence processes associated with assembled actin filaments and microtubules. Thus, there is an extended functional role for CCT with regard to its major folding substrates with a complex interplay between CCT as folding machine for tubulin/actin and as a modulator of processes involving the assembled cytoskeleton. As cell division, directed cell migration, and invasion are major drivers of cancer development and rely on the microtubule and actin filament components of the cytoskeleton, CCT activity is fundamentally linked to cancer. Furthermore, the CCT oligomer also folds proteins connected to cell cycle progression and interacts with several other proteins that are linked to cancer such as tumor-suppressor proteins and regulators of the cytoskeleton, while CCT monomer function can influence cell migration. Thus, understanding CCT activity is important for many aspects of cancer cell biology and may reveal new ways to target tumor growth and invasion.
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