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Frontiers in Molecular Biosciences

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https://www.readbyqxmd.com/read/28736730/new-insight-into-microrna-functions-in-cancer-oncogene-microrna-tumor-suppressor-gene-network
#1
REVIEW
Kecheng Zhou, Minxia Liu, Yi Cao
Tumorigenesis is a multi-step and complex process with multi-factors involved. Deregulated oncogenes and tumor suppressor genes (TSGs) induced by genetic and epigenetic factors are considered as the driving force in the development and progression of cancer. Besides, microRNAs (miRNAs) act vital roles in tumorigenesis through regulating some oncogenes and TSGs. Interestingly, miRNAs are also regulated by oncogenes and TSGs. Considering the entangled regulation, here we propose a new insight into these regulation relationships in cancer: oncogene-miRNA-TSG network, which further emphasizes roles of miRNA, as well as highlights the network regulation among oncogene, miRNA, and TSG during tumorigenesis...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28713815/bioinformatic-prediction-of-possible-targets-and-mechanisms-of-action-of-the-green-tea-compound-epigallocatechin-3-gallate-against-breast-cancer
#2
Xinqiang Song, Mu Zhang, Lei Chen, Qingsong Lin
Epigallocatechin-3-gallate (EGCG), a bioactive compound in green tea, is the most abundant and biologically active catechin, and it exerts multiple effects in humans through mechanisms that remain to be clarified. The present study used bioinformatics to identify possible mechanisms by which EGCG reduces risk of breast cancer. Possible human protein targets of EGCG were identified in the PubChem database, possible human gene targets were identified in the NCBI database, and then both sets of targets were analyzed using Ingenuity Pathway Analysis to predict molecular networks affected by EGCG in breast cancer...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28676851/aaa-atpases-in-protein-degradation
#3
REVIEW
Ravikiran S Yedidi, Petra Wendler, Cordula Enenkel
Proteolytic machineries containing multisubunit protease complexes and AAA-ATPases play a key role in protein quality control and the regulation of protein homeostasis. In these protein degradation machineries, the proteolytically active sites are formed by either threonines or serines which are buried inside interior cavities of cylinder-shaped complexes. In eukaryotic cells, the proteasome is the most prominent protease complex harboring AAA-ATPases. To degrade protein substrates, the gates of the axial entry ports of the protease need to be open...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28664160/new-techniques-for-ancient-proteins-direct-coupling-analysis-applied-on-proteins-involved-in-iron-sulfur-cluster-biogenesis
#4
Marco Fantini, Duccio Malinverni, Paolo De Los Rios, Annalisa Pastore
Direct coupling analysis (DCA) is a powerful statistical inference tool used to study protein evolution. It was introduced to predict protein folds and protein-protein interactions, and has also been applied to the prediction of entire interactomes. Here, we have used it to analyze three proteins of the iron-sulfur biogenesis machine, an essential metabolic pathway conserved in all organisms. We show that DCA can correctly reproduce structural features of the CyaY/frataxin family (a protein involved in the human disease Friedreich's ataxia) despite being based on the relatively small number of sequences allowed by its genomic distribution...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28660197/a-mighty-protein-extractor-of-the-cell-structure-and-function-of-the-p97-cdc48-atpase
#5
REVIEW
Yihong Ye, Wai Kwan Tang, Ting Zhang, Di Xia
p97/VCP (known as Cdc48 in S. cerevisiae or TER94 in Drosophila) is one of the most abundant cytosolic ATPases. It is highly conserved from archaebacteria to eukaryotes. In conjunction with a large number of cofactors and adaptors, it couples ATP hydrolysis to segregation of polypeptides from immobile cellular structures such as protein assemblies, membranes, ribosome, and chromatin. This often results in proteasomal degradation of extracted polypeptides. Given the diversity of p97 substrates, this "segregase" activity has profound influence on cellular physiology ranging from protein homeostasis to DNA lesion sensing, and mutations in p97 have been linked to several human diseases...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28642865/spinal-muscular-atrophy-from-defective-chaperoning-of-snrnp-assembly-to-neuromuscular-dysfunction
#6
REVIEW
Maia Lanfranco, Neville Vassallo, Ruben J Cauchi
Spinal Muscular Atrophy (SMA) is a neuromuscular disorder that results from decreased levels of the survival motor neuron (SMN) protein. SMN is part of a multiprotein complex that also includes Gemins 2-8 and Unrip. The SMN-Gemins complex cooperates with the protein arginine methyltransferase 5 (PRMT5) complex, whose constituents include WD45, PRMT5 and pICln. Both complexes function as molecular chaperones, interacting with and assisting in the assembly of an Sm protein core onto small nuclear RNAs (snRNAs) to generate small nuclear ribonucleoproteins (snRNPs), which are the operating components of the spliceosome...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28638822/extracellular-vesicles-in-renal-pathophysiology
#7
REVIEW
Margherita A C Pomatto, Chiara Gai, Benedetta Bussolati, Giovanni Camussi
Extracellular vesicles are a heterogeneous population of microparticles released by virtually all living cells which have been recently widely investigated in different biological fields. They are typically composed of two primary types (exosomes and microvesicles) and are recently commanding increasing attention as mediators of cellular signaling. Indeed, these vesicles can affect recipient cells by carrying and delivering complex cargos of biomolecules (including proteins, lipids and nucleic acids), protected from enzymatic degradation in the environment...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28634583/circular-rnas-biogenesis-function-and-role-in-human-diseases
#8
REVIEW
John Greene, Anne-Marie Baird, Lauren Brady, Marvin Lim, Steven G Gray, Raymond McDermott, Stephen P Finn
Circular RNAs (circRNAs) are currently classed as non-coding RNA (ncRNA) that, unlike linear RNAs, form covalently closed continuous loops and act as gene regulators in mammals. They were originally thought to represent errors in splicing and considered to be of low abundance, however, there is now an increased appreciation of their important function in gene regulation. circRNAs are differentially generated by backsplicing of exons or from lariat introns. Unlike linear RNA, the 3' and 5' ends normally present in an RNA molecule have been joined together by covalent bonds leading to circularization...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28611991/substrate-discrimination-by-clpb-and-hsp104
#9
Danielle M Johnston, Marika Miot, Joel R Hoskins, Sue Wickner, Shannon M Doyle
ClpB of E. coli and yeast Hsp104 are homologous molecular chaperones and members of the AAA+ (ATPases Associated with various cellular Activities) superfamily of ATPases. They are required for thermotolerance and function in disaggregation and reactivation of aggregated proteins that form during severe stress conditions. ClpB and Hsp104 collaborate with the DnaK or Hsp70 chaperone system, respectively, to dissolve protein aggregates both in vivo and in vitro. In yeast, the propagation of prions depends upon Hsp104...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28611990/structure-and-function-of-p97-and-pex1-6-type-ii-aaa-complexes
#10
REVIEW
Paul Saffert, Cordula Enenkel, Petra Wendler
Protein complexes of the Type II AAA+ (ATPases associated with diverse cellular activities) family are typically hexamers of 80-150 kDa protomers that harbor two AAA+ ATPase domains. They form double ring assemblies flanked by associated domains, which can be N-terminal, intercalated or C-terminal to the ATPase domains. Most prominent members of this family include NSF (N-ethyl-maleimide sensitive factor), p97/VCP (valosin-containing protein), the Pex1/Pex6 complex and Hsp104 in eukaryotes and ClpB in bacteria...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28589125/multifunctional-mitochondrial-aaa-proteases
#11
REVIEW
Steven E Glynn
Mitochondria perform numerous functions necessary for the survival of eukaryotic cells. These activities are coordinated by a diverse complement of proteins encoded in both the nuclear and mitochondrial genomes that must be properly organized and maintained. Misregulation of mitochondrial proteostasis impairs organellar function and can result in the development of severe human diseases. ATP-driven AAA+ proteins play crucial roles in preserving mitochondrial activity by removing and remodeling protein molecules in accordance with the needs of the cell...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28589124/a-multidisciplinary-phenotyping-and-genotyping-analysis-of-a-mapping-population-enables-quality-to-be-combined-with-yield-in-rice
#12
Mariafe Calingacion, Roland Mumm, Kevin Tan, Lenie Quiatchon-Baeza, Jeanaflor C T Concepcion, Jos A Hageman, Sangeeta Prakash, Melissa Fitzgerald, Robert D Hall
In this study a mapping population (F8) of ca 200 progeny from a cross between the commercial rice varieties Apo and IR64 has been both genotyped and phenotyped. A genotyping-by-sequencing approach was first used to identify 2,681 polymorphic SNP markers which gave dense coverage of the genome with a good distribution across all 12 chromosomes. The coefficient of parentage was also low, at 0.13, confirming that the parents are genetically distant from each other. The progeny, together with both parents, were grown under irrigated and water restricted conditions in a randomised block design...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28580359/the-diverse-aaa-machines-that-repair-inhibited-rubisco-active-sites
#13
REVIEW
Oliver Mueller-Cajar
Gaseous carbon dioxide enters the biosphere almost exclusively via the active site of the enzyme ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco). This highly conserved catalyst has an almost universal propensity to non-productively interact with its substrate ribulose 1,5-bisphosphate, leading to the formation of dead-end inhibited complexes. In diverse autotrophic organisms this tendency has been counteracted by the recruitment of dedicated AAA+ (ATPases associated with various cellular activities) proteins that all use the energy of ATP hydrolysis to remodel inhibited Rubisco active sites leading to release of the inhibitor...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28560213/tetrabutylphosphonium-bromide-reduces-size-and-polydispersity-index-of-tat2-sirna-nano-complexes-for-triticale-rnai
#14
Jordan T Pepper, Priti Maheshwari, Alicja Ziemienowicz, Paul Hazendonk, Igor Kovalchuk, François Eudes
Cell-penetrating peptides (CPPs) are short 8-30 amino-acid oligopeptides that act as effective transducers of macromolecular cargo, particularly nucleic acids. They have been implemented in delivering dsDNA, ssDNA, and dsRNA into animal and plant cells. CPPs and nucleic acids form nano-complexes that are often 100-300 nm in size but still effectively transit the cell membrane of animal cells, but are less effective with plant cells due to the plant cell wall. To overcome this obstacle, nano-complexes of the CPP Tat2 and various lengths of nucleic acid (21-mer siRNA duplex (dsRNA) to ~5...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28553638/torsin-atpases-harnessing-dynamic-instability-for-function
#15
Anna R Chase, Ethan Laudermilch, Christian Schlieker
Torsins are essential, disease-relevant AAA+ (ATPases associated with various cellular activities) proteins residing in the endoplasmic reticulum and perinuclear space, where they are implicated in a variety of cellular functions. Recently, new structural and functional details about Torsins have emerged that will have a profound influence on unraveling the precise mechanistic details of their yet-unknown mode of action in the cell. While Torsins are phylogenetically related to Clp/HSP100 proteins, they exhibit comparatively weak ATPase activities, which are tightly controlled by virtue of an active site complementation through accessory cofactors...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28536693/the-essential-role-of-clpxp-in-caulobacter-crescentus-requires-species-constrained-substrate-specificity
#16
Robert H Vass, Jacob Nascembeni, Peter Chien
The ClpXP protease is a highly conserved AAA+ degradation machine that is present throughout bacteria and in eukaryotic organelles. ClpXP is essential in some bacteria, such as Caulobacter crescentus, but dispensible in others, such as Escherichia coli. In Caulobacter, ClpXP normally degrades the SocB toxin and increased levels of SocB result in cell death. ClpX can be deleted in cells lacking this toxin, but these ΔclpX strains are still profoundly deficient in morphology and growth supporting the existence of additional important functions for ClpXP...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28523272/structural-elements-regulating-aaa-protein-quality-control-machines
#17
REVIEW
Chiung-Wen Chang, Sukyeong Lee, Francis T F Tsai
Members of the ATPases Associated with various cellular Activities (AAA+) superfamily participate in essential and diverse cellular pathways in all kingdoms of life by harnessing the energy of ATP binding and hydrolysis to drive their biological functions. Although most AAA+ proteins share a ring-shaped architecture, AAA+ proteins have evolved distinct structural elements that are fine-tuned to their specific functions. A central question in the field is how ATP binding and hydrolysis are coupled to substrate translocation through the central channel of ring-forming AAA+ proteins...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28523271/the-protein-chaperone-clpx-targets-native-and-non-native-aggregated-substrates-for-remodeling-disassembly-and-degradation-with-clpp
#18
Christopher J LaBreck, Shannon May, Marissa G Viola, Joseph Conti, Jodi L Camberg
ClpX is a member of the Clp/Hsp100 family of ATP-dependent chaperones and partners with ClpP, a compartmentalized protease, to degrade protein substrates bearing specific recognition signals. ClpX targets specific proteins for degradation directly or with substrate-specific adaptor proteins. Native substrates of ClpXP include proteins that form large oligomeric assemblies, such as MuA, FtsZ, and Dps in Escherichia coli. To remodel large oligomeric substrates, ClpX utilizes multivalent targeting strategies and discriminates between assembled and unassembled substrate conformations...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28516087/dna-sequence-analysis-in-clinical-medicine-proceeding-cautiously
#19
REVIEW
Moyra Smith
Delineation of underlying genomic and genetic factors in a specific disease may be valuable in establishing a definitive diagnosis and may guide patient management and counseling. In addition, genetic information may be useful in identification of at risk family members. Gene mapping and initial genome sequencing data enabled the development of microarrays to analyze genomic variants. The goal of this review is to consider different generations of sequencing techniques and their application to exome sequencing and whole genome sequencing and their clinical applications...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28487858/a-balanced-approach-to-adaptive-probability-density-estimation
#20
Julio A Kovacs, Cailee Helmick, Willy Wriggers
Our development of a Fast (Mutual) Information Matching (FIM) of molecular dynamics time series data led us to the general problem of how to accurately estimate the probability density function of a random variable, especially in cases of very uneven samples. Here, we propose a novel Balanced Adaptive Density Estimation (BADE) method that effectively optimizes the amount of smoothing at each point. To do this, BADE relies on an efficient nearest-neighbor search which results in good scaling for large data sizes...
2017: Frontiers in Molecular Biosciences
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