Special Issue "Molecular Chaperones 2.0"
Deadline for manuscript submissions: 31 December 2019.
Homeostasis is essential for maintaining cell function. For that purpose, proteins must fold to their native state in order to achieve functionality. Many heat shock proteins (HSPs) perform chaperone functions by stabilizing new proteins to ensure correct folding or by helping to refold proteins that were damaged by cell stress. Molecular chaperones belong to the family of conservative proteins with a high homology of the primary structure in both the prokaryote and eukaryote. HSPs are often classified according to their molecular weight and members include HSP90, HSP70, HSP60, and the small HSPs. Molecular chaperones have a large functional diversity. Their fundamental roles include de novo folding and the refolding of misfolded protein. Chaperones also regulate critical cellular processes, such as protein trafficking, protein degradation, protein complex assembly, and regulate functional proteins, such as steroid hormone receptors. The uniqueness of molecular chaperones results from their ability to interact with a very large number of different proteins, called clients. HSPs provide protection from cellular and environmental stress factors as molecular chaperones to maintain protein homeostasis. This Special Issue will include original research papers and outstanding reviews that show the role of molecular chaperones in the functionality of homeostasis in the cell.
Prof. Dr. Hideaki Itoh
Manuscript Submission Information
Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.
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- molecular chaperone
- Heat shock protein (HSPs)
- HSP90, HSP70, HSP60
- de novo folding
- misfolded protein
- protein trafficking
- protein degradation
- protein complex assembly
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
Review: Calnexin/calreticulin cycle: a structural perspective
Authors: Kalle Gehring, Guennadi Kozlov
Review: Molecular chaperones in cancer stem cells: determinants of stemness and targets for therapy
Authors: Alexander Kabakov, et al.
Review on the chaperone network in human cells is responsible for aggregate reactivation and the potential effects that post-translational modifications might have on its biological activity
Authors: ARTURO MUGA ， Fernando Moro, et al.
Review on Fine tuning: Effects of post-translational modification on chaperone proteins.
Authors: Holmes, William M.
Review on the Role of heat shock proteins in glaucoma
Authors: Teresa Tsai, Pia Grotegut, Sabrina Reinehr, Stephanie C. Joachim
Review Inhibitors of molecular chaperones in recipes of anti-cancer therapeutics
Authors: Maxim Shevtsov, et al.
Title: Role of the bacterial chaperone DnaK in cellular transformation, by
Authors: Davide Zella, et al.
Title: HSP90 plays a chaperone function using GTPase energy source
Authors: Hideaki Itoh
Title: Development of new HSP90 M-domain inhibitors
Authors: Ivanhoe Leung, Oi Wei Mak
Title: Immunomorphology and biomolecular evaluation of Heat Shock Proteins in thyroid diseases
Authors: Francesca Rappa, et al.
Title: Neuromuscular diseases due to chaperone dysfunction – a review and some new results
Authors: Jaakko Sarparanta, Per-Harald Jonson, Bjarne Udd, et al.
Title: HSP90 inhibition and drug transporter activities in cancer cells
Authors: Vincent E Sollars, et al.
Title: Epigenetic alterations for Heat shock protein (HSPs) in Cancer
Authors: Cho Hyun-Soo, et al.
Title: The endoplasmic reticulum chaperone GRP94 is involved in the lipidic phenotype of brain metastatic cells
Authors: Naiara Santana-Codina1,2,, Anna Marcé1, Laia Muixí1,, Claudia Nieva1,3, Mónica Marro3, David Sebastián4, Juan Pablo Muñoz4, Antonio Zorzano4, Angels Sierra5, *
1 Biological Clues of the Invasive and Metastatic Phenotype Group, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona E-08908, Spain.
2 Universitat Autònoma de Barcelona (UAB), Campus Bellaterra, Cerdanyola del Vallés, Barcelona E-08193, Spain.
3 ICFO - Institut de Ciències Fotòniques, Av. Carl Friedrich Gauss, 3. Castelldefels, Barcelona E-08860, Spain
4 Institute for Research in Biomedicine (IRB Barcelona), Universitat de Barcelona, and CIBERDEM, Barcelona, 08028, Catalonia, Spain
5 Laboratory of Molecular and Translational Oncology, Centre de Recerca Biomèdica CELLEX-CRBC- Institut d'Investigacions Biomèdiques August Pi i Sunyer-IDIBAPS, Barcelona E-08036, Spain.
Background: Metabolic alterations in cancer cells mechanistically underpin many aspects of malignant transformation and therapy resistance. Metabolic rewiring can happen as a consequence of the pressure exerted by the microenvironment, a key step in adaptation and survival of tumor metastatic cells. This phenomenon is even more important in the pathogenesis of brain metastasis, which happens in 40% of all diagnosed cancer cases as a consequence of the systemic dissemination of tumour cells and which correlates with poor prognosis and high morbidity (1). One of the main reasons for this poor prognosis is the difficulty in the identification of biomarkers that allow a more targeted therapy. In order to obtain a list of brain metastatic organ-specific genes, we performed transcriptomic analysis of breast cancer metastasis from patients and evaluated the differential expression of genes in brain metastasis in comparison to lung, bone and liver metastasis (2). To determine organ-specific de-regulated functions, we used a network approach to identify network parameters based on the whole human interactome (topology information) and internal connections between genes (functional
interpretation) (3,4). Over-expression of glucose regulated protein-94 (GRP94) predicted brain metastasis in breast carcinoma patients, either triple negative or ErbB2 positive tumors. Moreover, we identified a differential over-expression of proteins related to synthesis of Total Unsaturated Fatty Acids (TUSFA) in brain metastasis. Here, we investigated the role of GRP94 as a chaperone that mediates adaptation and survival of brain metastatic cells (BRM) to low glucose conditions.
Methods: To analyse the effects of GRP94 expression on progression and on the lipogenic phenotype of BrM, we used metastatic variants from human breast cancer cell lines (MDA-MB-435, MDA-MB-361 and SA52) and the highly brain metastatic cell line BRV5, which was obtained after five in vitro/in vivo rounds. We used Raman spectroscopy as a non-invasive technique to quantify Total Fatty Acids (TFA) and Total Unsaturated Fatty Acids (TUFA). Finally, we assessed fatty acid oxidation by 14C-palmitate oxidation assays and we identified by Western Blot some of the proteins involved in this lipidic phenotype.
Results: BrM cells present an increase in fatty acid content measured by Raman spectroscopy, which correlates with increased expression of proteins involved in fatty acid synthesis like SREBP-1 and LXRα. Furthermore, BrM cells presented a higher ability to oxidize fatty acids in basal and in glucose deprivation conditions, together with increased levels of ACOT-7. This phenotype correlated with increased mitochondrial mass and fusion in BrM cells which may promote higher mitochondrial efficiency. GRP94 knockdown increased glucose dependence and decreased etomoxir sensitivity which correlated with a down regulation ACOT7 in addition to reduce in vivo tumorigenicity.
Conclusions: Here, we show that GRP94 is directly implicated in lipid metabolism of brain metastatic cells. Overall, our data suggest that fatty acid oxidation may be a metabolic strategy to favor BrM growth and overcome stress induced by glucose starvation.