FEBS Letters
FEBS Letters RSS feed. FEBS Letters is one of the world's leading journals in biochemistry and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, hypotheses and research letters that merit urgent publication.FEBS Letters offers:• Faster publication: − Accepted articles are published online in 3 days − The print version of the article is published in 3 to 5 weeks after acceptance• Full-text article disclosure in HTML and PDF formats• Articles in Press are included in PubMed• Easy online manuscript submission system• Transparent online peer review and manuscript tracking system• No page charges• Free color figures Subject Coverage:The subject area of FEBS Letters is broad. It covers biochemistry (including protein chemistry, enzymology, nucleic acid chemistry, metabolism, and immunochemistry), structural biology, biophysics, computational biology (genomics, proteomics, bioinformatics), molecular genetics, molecular biology and molecular cell biology (signal transduction, intracellular traffic, regulation of cellular proliferation, cell-cell interactions) and systems biology. Studies on microbes, plants and animals at the molecular level are within the scope of FEBS Letters.Submitting Authors: Manuscripts can be submitted to FEBS Letters at: http://ees.elsevier.com/febsletters/
Updated: 8 years 20 weeks ago
Arabidopsis Yak1 protein (AtYak1) is a dual specificity protein kinase
Phosphorylation is the most frequent type of protein post-translational modification, which is often associated with the molecular activation/de-activation of signal-transduction pathways [1]. In higher eukaryotes, an estimated one third of all proteins are regulated by phosphorylation by protein kinases (PKs). The genomes of plant species encode more than 1000 PKs [2]. However, the substrates of only a small fraction of these kinases are known [3].
Therapeutic potential of the endoplasmic reticulum located and secreted CDNF/MANF family of neurotrophic factors in Parkinson’s disease
Parkinson’s disease (PD) is a progressive neurodegenerative disorder where dopamine (DA) neurons in the substantia nigra degenerate and die. Since no cure for PD exists, there is a need for disease-modifying drugs. Glial cell line-derived neurotrophic factor (GDNF) and related neurturin (NRTN) can protect and repair DA neurons in neurotoxin animal models of PD. However, GDNF was unable to rescue DA neurons in an α-synuclein model of PD, and both factors have shown modest effects in phase two clinical trials.
PIAS1-mediated sumoylation promotes STUbL-dependent proteasomal degradation of the human telomeric protein TRF2
Telomeres are the specialized nucleoprotein complexes at the ends of eukaryotic chromosomes, which are essential for chromosome integrity [1,2]. Mammalian telomeres consist of duplex tandem TTAGGG repeats with 3′ single-stranded G overhangs [3,4] and are tightly associated with the six-protein complex shelterin, thereby protecting chromosome ends from being recognized as sites of DNA damage [5,6]. In addition to the shelterin complex, telomeres are associated with a number of accessory factors that are involved in DNA metabolism [7].
Functional roles in -adenosyl--methionine binding and catalysis for active site residues of the thiostrepton resistance methyltransferase
The methylation of rRNA is vital to the structure and function of ribosomes across all domains of life [1]. Many of these modifications are carried out by methyltransferases that recruit S-adenosyl-l-methionine (SAM) for highly specific methylations of RNA base targets. Such enzymes are in various instances responsible for rRNA methylations that bring about bacterial resistance to certain ribosome-targeting antibiotics, noteworthy examples of which can be found in clinically relevant classes such as aminoglycosides and macrolides [2].
Europium as an inhibitor of Amyloid-β(1-42) induced membrane permeation
Alzheimer’s disease (AD) is the most common form of dementia worldwide, with a global cost of over $600 billion in 2012 [1]. The pathological hallmarks of AD include the loss of neurons, the accumulation of neuritic plaques composed of extracellular, fibrillar Amyloid-beta peptide (Aβ), and the deposition of intraneuronal neurofibrillary tangles composed of tau [2]. Aβ1–42 (Aβ42) is the predominant variant deposited in AD brains.
MicroRNA-145 regulates osteoblastic differentiation by targeting the transcription factor Cbfb
Skeletal development and bone regeneration depend on the properties of osteoblasts derived from mesenchymal stem cells (MSCs) [1–5]. Bone is routinely remodeled throughout life, requiring the coordinated expression of many genes in response to many physiological signals. Osteoblastic differentiation from MSCs is regulated by multiple signaling pathways that are activated ligands such as bone morphogenetic proteins (BMPs), fibroblast growth factors (FGFs) and Wnts, which directly activate runt-related transcription factor 2 (Runx2) [6–8].
Emerging targets for combination therapy in melanomas
Cutaneous melanomas are often difficult to treat when diagnosed in advanced stages. Melanoma cells adapt to survive in extreme environmental conditions and are among the tumors with larger genomic instability. Here we discuss some intrinsic and extrinsic mechanisms of resistance of melanoma cells to both conventional and target therapies, such as autophagy, adaptation to endoplasmic reticulum stress, metabolic reprogramming, mechanisms of tumor repopulation and the role of extracellular vesicles in this later phenomenon.
Autophagy and proteins involved in vesicular trafficking
Autophagy is an intracellular degradation system that, as a basic mechanism it delivers cytoplasmic components to the lysosomes in order to maintain adequate energy levels and cellular homeostasis. This complex cellular process is activated by low cellular nutrient levels and other stress situations such as low ATP levels, the accumulation of damaged proteins or organelles, or pathogen invasion. Autophagy as a multistep process involves vesicular transport events leading to tethering and fusion of autophagic vesicles with several intracellular compartments.
Asparagine deamidation reduces DNA-binding affinity of the Scr homeodomain
Asparagine (Asn) residues in proteins are prone to deamidation, isomerization, racemization, and peptide bond cleavage, under physiological conditions in the absence of enzymatic catalysis [1,2]. Deamidation to form aspartate or iso-aspartate (isoAsp) is the most common Asn modification. Conversion of Asn to Asp or isoAsp introduces one additional negative charge into the protein. In addition, iso-aspartate forms a non-native β-peptide backbone linkage through the γ-carboxylate, rather than the α-carboxylate [3].
High pressure promotes alpha-synuclein aggregation in cultured neuronal cells
Many neurodegenerative diseases, such as Parkinson’s, Mutiple System Atrophy, Dementia with Lewy Bodies, and Amyotrophic Lateral Sclerosis, are caused by protein aggregates composed largely of the protein α-synuclein (AS). This group of neurodegenerative diseases, referred to as Lewy Body Diseases are found in patients that carry point mutations or multiple copies of the AS gene [1–9]. However, genetic mutations of AS account only for a small percentage of pathologies and two major environmental causes linked to sporadic LBD have been identified.
Ganglioside GM3 as a gatekeeper of obesity-associated insulin resistance: Evidence and mechanisms
Gangliosides constitute a large family of sialic acid-containing glycosphingolipids which play a key regulatory role in a diverse array of cellular processes, including receptor-associated signalling. Accordingly, the aberrant production of the ganglioside GM3 has been linked to pathophysiological changes associated with obesity, which in turn can lead to metabolic disorders such as insulin resistance and type 2 diabetes mellitus. This review examines the role of GM3 in mediating obesity-induced perturbations in metabolic function, including impaired insulin action.
Establishing diversity in the dopaminergic system
Midbrain dopaminergic neurons (MbDNs) modulate cognitive processes, regulate voluntary movement, and encode reward prediction errors and aversive stimuli. While the degeneration of MbDNs underlies the motor defects in Parkinson’s disease, imbalances in dopamine levels are associated with neuropsychiatric disorders such as depression, schizophrenia and substance abuse. In recent years, progress has been made in understanding how MbDNs, which constitute a relatively small neuronal population in the brain, can contribute to such diverse functions and dysfunctions.
Dissecting the functional roles of the conserved NXXE and HXE motifs of the ADP-dependent glucokinase from
Glucose phosphorylation into glucose-6-phosphate (glucose-6-P) constitutes the first step of glycolysis, the central metabolic pathway in all three domains of life. While most glucokinases use adenosine triphosphate (ATP) as the phosphoryl donor, several archaea of the Euryarchaeota possess an ADP-dependent glucokinase as part of a variety of modifications on their Embden–Meyerhof pathway [1]. Despite the lack of sequence similarity between these glucokinases and their ATP-dependent counterparts, the three-dimensional structure resolution of several of these ADP-dependent enzymes have allowed their classification as members of the ribokinase superfamily [2].
The zinc-finger protein SPT4 interacts with SPT5L/KTF1 and modulates transcriptional silencing in
In plants, the RNA-directed DNA methylation (RdDM) pathway can achieve the transcriptional silencing of transposons and endogenous repeats. This process involves the generation of both short and long non-coding RNAs that are synthesised by two plant-specific RNA polymerases (RNAPs) termed RNAPIV and RNAPV [1–6]. Usually, RNAPIV produces the precursors of 24-nt siRNAs, which are bound by ARGONAUTE4 (AGO4) and interact with long non-coding RNA transcripts of RNAPV. This results in de novo DNA methylation of homologous genomic sites.
-fucosylation of CCN1 is required for its secretion
Matricellular protein CCN1, also known as Cyr61, is a member of the growth factor-inducible immediate-early genes and belongs to CCN family proteins, which are the secreted cysteine-rich proteins [1–4]. Human CCN family contains six members, CCN1–6 [4,5]. All CCN family proteins have an N-terminal signal peptide, followed by four functional domains—insulin-like growth factor-binding protein (IGFBP) N-terminal domain, von Willebrand factor type C repeat (vWC), thrombospondin type-1 repeat (TSR1), and cysteine knot motif (CT) in order—except CCN5, which lacks CT [5–7].
The regulatory role of B cells in autoimmunity, infections and cancer: Perspectives beyond IL10 production
The term regulatory B cells (B regs) is ascribed to a heterogeneous population of B cells with the function of suppressing inflammatory responses. They have been described mainly during the last decade in the context of different immune-mediated diseases. Most of the work on B regs has been focused on IL-10-producing B cells. However, B cells can exert regulatory functions independently of IL-10 production. Here we discuss the phenotypes, development and effector mechanisms of B regs and advances in their role in autoimmunity, infections and cancer.
Structural insights into the loss of catalytic competence in pectate lyase activity at low pH
Pectate lyases are carbon-oxygen lyases that harness anti-β-elimination chemistry to cleave the α-1,4 glycosidic linkage between d-galacturonate (GalA) residues in the homogalacturonan region of the plant polysaccharide pectin [1]. In the reaction scheme below R and R′ are additional α-1,4 linked GalA residues.Pectate lyases play a pivotal role in remodelling and recycling the pectin polysaccharides present as insoluble composites in plant cell walls, accelerating rates of reaction by factors exceeding 1017 fold and cleaving one of the most stable bonds in nature [2].
A role of astrocytes in mediating postnatal neurodegeneration in Glutaric acidemia-type 1
Astrocytes are crucial for postnatal development of neuronal networks, axon myelination and neurovascular structures. Defects in astrocyte generation or maturation are associated with severe neurological developmental disorders. Glutaric acidemia type I (GAI), an inherited neurometabolic disorder characterized by accumulation of glutaric (GA) and 3-hydroxyglutaric acids, shows a paradigmatic postnatal neuropathology characterized by massive degeneration of neurons in the striatum. While the disorder is caused by genetic mutations on glutaryl-CoA dehydrogenase, the neurological defects usually start months after birth.
Identification of an -acetylglucosamine kinase essential for UDP--acetylglucosamine salvage synthesis in
In eukaryotes, a wide variety of physiologically important glycans and glycoconjugates (e.g., cell wall chitin, extracellular matrix polymers, most secreted glycoproteins, and certain cytosolic or nucleic proteins) contain an N-acetylglucosamine (GlcNAc) moiety that is derived from uridine diphosphate (UDP)-GlcNAc [1–3]. UDP-GlcNAc is synthesized de novo from a glycolytic intermediate (fructose-6-phosphate; Fru-6P). Through transamination, acetylation, and conversion of phosphate, UDP-GlcNAc is formed by the conversion of GlcNAc-1-phosphate (GlcNAc-1P) and uridine triphosphate [4].
Crystal structure of human nuclear pore complex component NUP43
In eukaryotic cells, the nuclear envelope separates the nucleus from the cytoplasm and controls traffic between both, such as the transport of mRNAs and ribosomal proteins [1,2]. During cell mitosis, the nuclear envelope disassembles completely, and reassembles step by step at the end of mitosis. The nuclear pore complex (NPC), which is formed by several sub complexes, is embedded into the nuclear envelope [3–5]. The components of the mammalian NPC were identified and proteomically analyzed in 2002 [3].