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International Review of Cell and Molecular Biology

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https://www.readbyqxmd.com/read/28215535/ambra1-a-novel-bh3-like-protein-new-insights-into-the-ambra1-bcl2-family-proteins-relationship
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28109326/from-the-evolution-of-protein-sequences-able-to-resist-self-assembly-to-the-prediction-of-aggregation-propensity
#14
F Bemporad, M Ramazzotti
Folding of polypeptide chains into biologically active entities is an astonishingly complex process, determined by the nature and the sequence of residues emerging from ribosomes. While it has been long believed that evolution has pressed genomes so that specific sequences could adopt unique, functional three-dimensional folds, it is now clear that complex protein machineries act as quality control system and supervise folding. Notwithstanding that, events such as erroneous folding, partial folding, or misfolding are frequent during the life of a cell or a whole organism, and they can escape controls...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28069137/mitochondria-in-multiple-sclerosis-molecular-mechanisms-of-pathogenesis
#15
S Patergnani, V Fossati, M Bonora, C Giorgi, S Marchi, S Missiroli, T Rusielewicz, M R Wieckowski, P Pinton
Mitochondria, the organelles that function as the powerhouse of the cell, have been increasingly linked to the pathogenesis of many neurological disorders, including multiple sclerosis (MS). MS is a chronic inflammatory demyelinating disease of the central nervous system (CNS) and a leading cause of neurological disability in young adults in the western world. Its etiology remains unknown, and while the inflammatory component of MS has been heavily investigated and targeted for therapeutic intervention, the failure of remyelination and the process of axonal degeneration are still poorly understood...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28069136/the-inflammatory-signal-adaptor-ripk3-functions-beyond-necroptosis
#16
K Moriwaki, F K-M Chan
Receptor interacting protein kinase 3 (RIPK3) is an essential serine/threonine kinase for necroptosis, a type of regulated necrosis. A variety of stimuli can cause RIPK3 activation through phosphorylation. Activated RIPK3 in turn phosphorylates and activates the downstream necroptosis executioner mixed lineage kinase domain-like (MLKL). Necroptosis is a highly inflammatory type of cell death because of the release of intracellular immunogenic contents from disrupted plasma membrane. Indeed, RIPK3-deficient mice exhibited reduced inflammation in many inflammatory disease models...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28069135/epigenetic-control-of-gene-expression-in-maize
#17
J Huang, J S Lynn, L Schulte, S Vendramin, K McGinnis
Epigenetic gene regulation is important for proper development and gene expression in eukaryotes. Maize has a large and complex genome that includes abundant repetitive sequences which are frequently silenced by epigenetic mechanisms, making it an ideal organism to study epigenetic gene regulation. Epigenetic modifications are chromosome-bound, heritable changes to the genome that do not affect the DNA sequence, and can include DNA methylation, histone modification, and RNA processing. Our appreciation and understanding of epigenetic regulation has grown with the field since its inception ∼65 years ago...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28069134/the-multifaceted-contributions-of-chromatin-to-hiv-1-integration-transcription-and-latency
#18
E De Crignis, T Mahmoudi
The capacity of the human immunodeficiency virus (HIV-1) to establish latent infections constitutes a major barrier to the development of a cure for HIV-1. In latent infection, replication competent HIV-1 provirus is integrated within the host genome but remains silent, masking the infected cells from the activity of the host immune response. Despite the progress in elucidating the molecular players that regulate HIV-1 gene expression, the mechanisms driving the establishment and maintenance of latency are still not fully understood...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28069133/bh3-only-proteins-in-health-and-disease
#19
J A Glab, G W Mbogo, H Puthalakath
BH3-only proteins are proapoptotic members of the broader Bcl-2 family, which promote cell death by directly or indirectly activating Bax and Bak. The expression of BH3-only proteins is regulated both transcriptionally and posttranscriptionally in a cell type-specific and a tissue-specific manner. Research over the last 20 years has provided significant insights into their roles in tissue homeostasis and various pathologies, which in turn has led to the development of novel therapeutics for numerous diseases...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28069132/molecular-regulation-of-the-spindle-assembly-checkpoint-by-kinases-and-phosphatases
#20
G Manic, F Corradi, A Sistigu, S Siteni, I Vitale
The spindle assembly checkpoint (SAC) is a surveillance mechanism contributing to the preservation of genomic stability by monitoring the microtubule attachment to, and/or the tension status of, each kinetochore during mitosis. The SAC halts metaphase to anaphase transition in the presence of unattached and/or untensed kinetochore(s) by releasing the mitotic checkpoint complex (MCC) from these improperly-oriented kinetochores to inhibit the anaphase-promoting complex/cyclosome (APC/C). The reversible phosphorylation of a variety of substrates at the kinetochore by antagonistic kinases and phosphatases is one major signaling mechanism for promptly turning on or turning off the SAC...
2017: International Review of Cell and Molecular Biology
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