| 1. |
- 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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| 2. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
- 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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| 6. |
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