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International Review of Cell and Molecular Biology

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https://www.readbyqxmd.com/read/28325216/an-update-on-src-family-of-nonreceptor-tyrosine-kinases-biology
#1
J Espada, J Martín-Pérez
The members of the Src family of nonreceptor tyrosine kinases (SFKs) are implicated in multiple signaling processes that regulate key cellular functions, including proliferation, migration, differentiation, and survival. SFKs are activated by a large number of receptors for growth factors, cytokines, steroid hormones, G protein-coupled receptors, and also by adhesion proteins and other signaling partners. Through their common modular kinase an adapter protein domains, SFKs critically contribute to diversify different signal inputs, weaving a complex and dynamic network of cellular responses...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28325215/new-insights-into-cellular-stress-responses-to-environmental-metal-toxicants
#2
H-R Park, R Oh, P Wagner, R Panganiban, Q Lu
Exposures to metal toxicants in the environment disrupt normal physiological functions and have been linked to the development of a myriad of human diseases. While the molecular and cellular mechanisms underlying metal toxicities remain to be fully understood, it is well appreciated that metal toxicants induce cellular stresses and that how cells respond to the stresses plays an important role in metal toxicity. In this review, we focus on how metal exposures induce stresses in the endoplasmic reticulum (ER) to elicit the unfolded protein response (UPR)...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28325214/antibody-based-cancer-therapy-successful-agents-and-novel-approaches
#3
D Hendriks, G Choi, M de Bruyn, V R Wiersma, E Bremer
Since their discovery, antibodies have been viewed as ideal candidates or "magic bullets" for use in targeted therapy in the fields of cancer, autoimmunity, and chronic inflammatory disorders. A wave of antibody-dedicated research followed, which resulted in the clinical approval of a first generation of monoclonal antibodies for cancer therapy such as rituximab (1997) and cetuximab (2004), and infliximab (2002) for the treatment of autoimmune diseases. More recently, the development of antibodies that prevent checkpoint-mediated inhibition of T cell responses invigorated the field of cancer immunotherapy...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28325213/mitochondrion-a-common-organelle-for-distinct-cell-deaths
#4
Z Wang, C Figueiredo-Pereira, C Oudot, H L A Vieira, C Brenner
Mitochondria are deeply involved in cell fate decisions via their multiple roles in metabolism, cell growth, and cell death. In healthy cells, these functions are highly regulated to provide sufficient energy for cell function, maintain cell homeostasis, and avoid undesirable cell death. This is achieved by an orchestrated cooperation of cellular and molecular mechanisms such as mitochondrial mass control (mitophagy vs biogenesis), oxidative phosphorylation, redox and calcium homeostasis, and the balance between pro- and antiapoptotic proteins...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28325212/chemokine-receptor-signaling-and-the-hallmarks-of-cancer
#5
R A Lacalle, R Blanco, L Carmona-Rodríguez, A Martín-Leal, E Mira, S Mañes
The chemokines are a family of chemotactic cytokines that mediate their activity by acting on seven-transmembrane-spanning G protein-coupled receptors. Both the ability of the chemokines and their receptors to form homo- and heterodimers and the promiscuity of the chemokine-chemokine receptor interaction endow this protein family with enormous signaling plasticity and complexity that are not fully understood at present. Chemokines were initially identified as essential regulators of homeostatic and inflammatory trafficking of innate and adaptive leucocytes from lymphoid organs to tissues...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28325211/stat-transcription-factors-in-t-cell-control-of-health-and-disease
#6
R Goswami, M H Kaplan
The Jak-STAT pathway is one of many pleiotropic signaling pathways that plays an important role in organismal development and in response to changing environmental cues. As a key signaling cascade for cytokines and growth factors, Jak-STAT plays central role in the innate and adaptive immune system. Cytokines control the stability, commitment, and maturation of cytotoxic and helper T cells, parts of the adaptive immune system that mediate immunity to pathogens and are linked to inflammatory diseases. Dysregulation of Jak-STAT protein expression or function leads to autoimmunity, allergic diseases, and cancer...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28325210/breast-cancer-immunology-and-immunotherapy-current-status-and-future-perspectives
#7
L de la Cruz-Merino, M Chiesa, R Caballero, F Rojo, N Palazón, F H Carrasco, V Sánchez-Margalet
Cancer immunology has gained renewed interest in the past few years due to emerging findings on mechanisms involved in tumoral immune evasion. Indisputably, immune edition is currently considered a critical hallmark of cancer. Basic research has revealed new targets which can be modulated in the clinical setting with new compounds and strategies. As recent evidence confirms, breast cancer (BC) is a complex and heterogeneous disease in which host immune responses play a substantial role. T-infiltrating lymphocytes measurement is suggested as a powerful new tool necessary to predict early BC evolution, especially in HER2-positive and triple negative subtypes...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28215535/ambra1-a-novel-bh3-like-protein-new-insights-into-the-ambra1-bcl2-family-proteins-relationship
#8
A Di Rita, F Strappazzon
Cellular homeostasis swings like a pendulum backward and forward between life and death. Two of the main processes, which regulate this equilibrium, are autophagy and apoptosis. While autophagy is a highly conserved self-digestion mechanism that mediates degradation of damaged or surplus components, apoptosis is a programmed cell suicide in which typical death signals induce the elimination of undesired cells. Both these processes are highly regulated by complex molecular machineries, including some common proteins whose "dual role" favors one process or the other...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28215534/immunomodulatory-activity-of-vegf-in-cancer
#9
A Lapeyre-Prost, M Terme, S Pernot, A-L Pointet, T Voron, E Tartour, J Taieb
The ability of tumor cells to escape tumor immunosurveillance contributes to cancer development. Factors produced in the tumor microenvironment create "tolerizing" conditions and thereby help the tumor to evade antitumoral immune responses. VEGF-A, already known for its major role in tumor vessel growth (neoangiogenesis), was recently identified as a key factor in tumor-induced immunosuppression. In particular, VEGF-A fosters the proliferation of immunosuppressive cells, limits T-cell recruitment into tumors, and promotes T-cell exhaustion...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28215533/plastid-protein-targeting-preprotein-recognition-and-translocation
#10
P Chotewutmontri, K Holbrook, B D Bruce
Eukaryotic organisms are defined by their endomembrane system and various organelles. The membranes that define these organelles require complex protein sorting and molecular machines that selectively mediate the import of proteins from the cytosol to their functional location inside the organelle. The plastid possibly represents the most complex system of protein sorting, requiring many different translocons located in the three membranes found in this organelle. Despite having a small genome of its own, the vast majority of plastid-localized proteins is nuclear encoded and must be posttranslationally imported from the cytosol...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28215532/consequences-of-keratin-phosphorylation-for-cytoskeletal-organization-and-epithelial-functions
#11
M S Sawant, R E Leube
Intermediate filaments are major phosphoproteins. The complex patterns of intermediate filament phosphorylation make up a poorly understood code reflecting cytoskeletal properties and cellular function through an intense crosstalk with multiple signaling pathways. This review focuses on the epithelial keratin intermediate filaments highlighting the tight-knit relationship of keratin phosphorylation and network organization during cell division and apoptosis, and the importance of keratin phosphorylation during epithelial stress responses...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28215531/smac-mimetics-to-therapeutically-target-iap-proteins-in-cancer
#12
S Fulda
Inhibitor of Apoptosis (IAP) proteins are overexpressed in a variety of human cancers. Therefore, they are considered as promising targets for the design of therapeutic strategies. Smac mimetics mimic the endogenous mitochondrial protein Smac that antagonizes IAP proteins upon its release into the cytosol. Multiple preclinical studies have documented the ability of Smac mimetics to either directly induce cell death of cancer cells or to prime them to agents that trigger cell death. At present, several Smac mimetics are being evaluated in early clinical trials...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28215530/rationale-for-the-combination-of-dendritic-cell-based-vaccination-approaches-with-chemotherapy-agents
#13
I Truxova, M Hensler, P Skapa, M J Halaska, J Laco, A Ryska, R Spisek, J Fucikova
Owing to their central role in the initiation and regulation of antitumor immunity, dendritic cells (DCs) have been widely tested for use in cancer immunotherapy. Despite several encouraging clinical applications, existing DC-based immunotherapy efforts have yielded inconsistent results. Recent work has identified strategies that may allow for more potent DC-based vaccines, such as the combination with antitumor agents that have the potential to synergistically enhance DC functions. Selected cytotoxic agents may stimulate DCs either by directly promoting their maturation or through the induction of immunogenic tumor cell death...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28215529/new-insights-into-the-roles-of-retinoic-acid-signaling-in-nervous-system-development-and-the-establishment-of-neurotransmitter-systems
#14
E Zieger, M Schubert
Secreted chiefly from the underlying mesoderm, the morphogen retinoic acid (RA) is well known to contribute to the specification, patterning, and differentiation of neural progenitors in the developing vertebrate nervous system. Furthermore, RA influences the subtype identity and neurotransmitter phenotype of subsets of maturing neurons, although relatively little is known about how these functions are mediated. This review provides a comprehensive overview of the roles played by RA signaling during the formation of the central and peripheral nervous systems of vertebrates and highlights its effects on the differentiation of several neurotransmitter systems...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28109332/structural-characteristics-of-%C3%AE-synuclein-oligomers
#15
N Cremades, S W Chen, C M Dobson
Oligomeric forms of amyloid aggregates have been detected in the brains and tissues of patients suffering from neurodegenerative disorders such as Parkinson's disease, and it is widely thought that such species are key pathogenic agents in the development and spreading of the disease; however, the study of these species has been proven to be extremely challenging, primarily as a result of their intrinsically transient nature and high levels of heterogeneity. Identifying the structural nature and the details of the mechanisms of formation and interconversion of individual oligomeric species, particularly those with high toxicity, is of fundamental importance not only for understanding the mechanisms of protein misfolding and amyloid aggregation but also for the identification of diagnostic and therapeutic targets...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28109331/protein-aggregation-and-molecular-crowding-perspectives-from-multiscale-simulations
#16
F Musiani, A Giorgetti
Cells are extremely crowded environments, thus the use of diluted salted aqueous solutions containing a single protein is too simplistic to mimic the real situation. Macromolecular crowding might affect protein structure, folding, shape, conformational stability, binding of small molecules, enzymatic activity, interactions with cognate biomolecules, and pathological aggregation. The latter phenomenon typically leads to the formation of amyloid fibrils that are linked to several lethal neurodegenerative diseases, but that can also play a functional role in certain organisms...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28109330/the-structure-of-mammalian-prions-and-their-aggregates
#17
E Vázquez-Fernández, H S Young, J R Requena, H Wille
Prion diseases, such as Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy in cattle, chronic wasting disease in cervids (i.e., deer, elk, moose, and reindeer), and sheep scrapie, are caused by the misfolding of the cellular prion protein (PrP(C)) into a disease-causing conformer (PrP(Sc)). PrP(C) is a normal, GPI-anchored protein that is expressed on the surface of neurons and other cell types. The structure of PrP(C) is well understood, based on studies of recombinant PrP, which closely mimics the structure of native PrP(C)...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28109329/what-makes-a-prion-infectious-proteins-from-animals-to-yeast
#18
K S MacLea
While philosophers in ancient times had many ideas for the cause of contagion, the modern study of infective agents began with Fracastoro's 1546 proposal that invisible "spores" spread infectious disease. However, firm categorization of the pathogens of the natural world would need to await a mature germ theory that would not arise for 300 years. In the 19th century, the earliest pathogens described were bacteria and other cellular microbes. By the close of that century, the work of Ivanovsky and Beijerinck introduced the concept of a virus, an infective particle smaller than any known cell...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28109328/the-nucleation-of-protein-aggregates-from-crystals-to-amyloid-fibrils
#19
Alexander K Buell
The condensation and aggregation of individual protein molecules into dense insoluble phases is of relevance in such diverse fields as materials science, medicine, structural biology and pharmacology. A common feature of these condensation phenomena is that they usually are nucleated processes, i.e. the first piece of the condensed phase is energetically costly to create and hence forms slowly compared to its subsequent growth. Here we give a compact overview of the differences and similarities of various protein nucleation phenomena, their theoretical description in the framework of colloid and polymer science and their experimental study...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28109327/effects-of-intrinsic-and-extrinsic-factors-on-aggregation-of-physiologically-important-intrinsically-disordered-proteins
#20
L Breydo, J M Redington, V N Uversky
Misfolding and aggregation of proteins and peptides play an important role in a number of diseases as well as in many physiological processes. Many of the proteins that misfold and aggregate in vivo are intrinsically disordered. Protein aggregation is a complex multistep process, and aggregates can significantly differ in morphology, structure, stability, cytotoxicity, and self-propagation ability. The aggregation process is influenced by both intrinsic (e.g., mutations and expression levels) and extrinsic (e...
2017: International Review of Cell and Molecular Biology
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