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
Extracellular heat shock protein 70 promotes osteogenesis of human mesenchymal stem cells through activation of the ERK signaling pathway
Management of fracture nonunion or bone defects is one of the most challenging clinical problems in orthopedic trauma. The incidence of nonunion or bone defects following fractures is increasing. Fracture nonunion or bone defects can be caused by infection, tumor resection, and skeletal abnormalities [1]. Despite advanced and optimized surgical procedures, approximately 5–10% of fractures sustained annually in the United States fail to complete the bony union process [2]. From a physiological viewpoint, growth factors, osteoprogenitor cells, and the extracellular matrix play a crucial role in creating the foundation for successful bone healing.
Global DNA hypomethylation coupled to cellular transformation and metastatic ability
DNA methylation is important for epigenetic gene regulation and implicated in many biological processes, such as early embryonic development, cell differentiation, and zygotic and somatic cell reprogramming [1,2]. In addition, the pathogenesis of many types of disease, including cancer, has been suggested to be affected by DNA methylation status [2,3]. Circumstantial evidence concerning the DNA methylation status in malignant tumor cells is available; however, most is derived from clinical samples of established tumors.
Unusual effects of crowders on heme retention in myoglobin
The heme prosthetic group is one of the most diverse cofactors found in nature, catering to a wide range of essential biological functions viz. oxygen transport, storage, catalysis and electron transfer, etc. Of the different heme-based metalloproteins that exist, myoglobin (Mb), involved in oxygen storage, is one of the most extensively studied biomolecules and has long been considered a paradigm for understanding the structural and functional characteristics of such proteins [1–3]. One of the biggest obstacles/deterrents in the study of Mb has been the loss of heme under denaturing conditions, with the cofactor known to impart significant stability to the apo-protein [4–7].
Down-regulation of 5S rRNA by miR-150 and miR-383 enhances c-Myc–rpL11 interaction and inhibits proliferation of esophageal squamous carcinoma cells
As one of the most common and fatal malignancies in the world, esophageal squamous cell carcinoma (ESCC) shows a relatively high incidence in Asian including China [1]. Cigarette smoking, heavy alcoholic consumption, micro-nutrient deficiency as well as dietary carcinogen exposure have been identified as main environmental etiological factors of ESCC [1–3]. However, only a part of exposed individuals eventually developed ESCC, indicating that host genetic differences may also contribute to ESCC carcinogenesis [4–6].
High-methionine diets accelerate atherosclerosis by HHcy-mediated FABP4 gene demethylation pathway via DNMT1 in ApoE mice
Epidemiological evidence suggests that hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis [1]. Numerous mechanisms have been suggested to explain the pathogenesis of homocysteine (Hcy)-associated atherosclerosis, including inflammatory injury and dyslipidemia [2–4]. However, the exact mechanism of lipid disturbances with HHcy remains unclear.
Targeting cholesterol with β-cyclodextrin sensitizes cancer cells for apoptosis
A single cancer cell left behind after surgery and/or chemotherapy could cause the recurrence of cancer [1]. Therefore, the aim of cancer chemotherapy must be to eliminate all cancer cells. Given the heterogeneity of cancer cells in a tumor, it is difficult to eliminate all cancer cells by a single agent targeting a particular gene product [2]. Thus, we developed a 2-deoxy glucose–ABT-263 (2DG–ABT) combination therapy [3]. This combination targets mitochondria directly, activating Bak to release cytochrome c into the cytosol where it forms the apoptosome, a protease complex that destroys numerous proteins.
Leucine-rich repeat 2 of human Toll-like receptor 4 contains the binding site for inhibitory monoclonal antibodies
Toll-like receptor 4 (TLR4) is an indispensable receptor for the recognition of lipopolysaccharide (LPS), a cell wall component of Gram-negative bacteria [1]. In response to an invading pathogenic microorganism, its signal activates the innate immune system, leading to the induction of adaptive immunity via the secretion of cytokines and the up-regulation of antigen presentation [1–4]. However, the excessive responses can cause a systemic inflammatory response syndrome such as sepsis. In addition, the collateral infection plays a non-negligible role on the pathogenesis of causative inflammatory disease by driving inflammatory responses.
Binding and entry of toxin B is mediated by multiple domains
Clostridium difficile (C. difficile) is a gram-positive, anaerobic bacillus that causes a variety of illnesses, dubbed collectively as C. difficile associate diseases (CDADs) [1]. Disease pathology is most frequently associated with C. difficile toxin B (TcdB) [2], however TcdB negative, C. difficile toxin A (TcdA) positive strains have been clinically isolated [3]. TcdA (2710 amino acid residues) and TcdB (2366 amino acid residues) are protein exotoxins which belong to the family of large clostridial glucosylating toxins (LCTs) [4,5].
Global mapping of the regulatory interactions of histone residues
As the structural units of chromatin, the core histones (H3, H4, H2A, and H2B) play a critical role in the epigenetic regulation of DNA. The biological significance and universality of their function are reflected by the remarkably high evolutionary conservation of the protein sequences from yeast to humans. The amino acid residues of histones can be partitioned into four major geographical domains: buried, disk (protein surface that does not contact DNA), lateral (protein surface that contacts DNA), and tail (protruding unstructured region).
MgcRacGAP inhibition stimulates JAK-dependent STAT3 activity
Male germ cell Rac GTPase Activating Protein (MgcRacGAP) functions as a GAP for Rac1 and other Rho family guanosine triphosphatases (GTPases) [1,2], meaning that it stimulates the intrinsic GTPase activity of the target Rho proteins switching them from their active GTP-bound form to inactive GDP-bound form [3]. Together with the kinesin MKLP1, MgcRacGAP forms the evolutionary conserved heterotetrameric complex centralspindlin that controls cytokinesis [1,2,4]. The complex binds to the microtubule-based mitotic spindle, initiating the formation of the central spindle.
Mir-302c mediates influenza A virus-induced IFNβ expression by targeting NF-κB inducing kinase
Influenza A virus (IAV) is a leading cause of respiratory illness in humans. IAV is responsible for seasonal epidemics and periodic pandemics that have serious economic impact [1]. Influenza A virus infection triggers intra- and extracellular receptors to elicit type-I interferon (IFNα/β) that represents a critical first line of defense against influenza infection [2].
Ventral midbrain dopaminergic neurons: From neurogenesis to neurodegeneration
Ventral midbrain dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc, A9 group), ventral tegmental area (VTA, A10 group) and the retrorubral field (RRF, A8 group) are a group of closely related neurons that share developmental profiles and origin. The neural circuits established by DA neurons include the nigrostriatal pathway that connects SNpc with the striatum, the mesolimbic pathway that connects DA neurons in VTA with the nucleus accumbens (NAc) and the limbic systems, and the mesocortical pathway that connect VTA neurons with the prefrontal cortex (Fig.
The steroid receptor RNA activator protein (SRAP) controls cancer cell migration/motility
The steroid receptor RNA activator (SRA) was first identified in 1999 as a non-coding RNA able to increase the activity of steroid receptors [1]. Since then, many studies have investigated the mechanisms of action of this functional RNA [2–8]. Through its core sequence (corresponding to exons 2-3-4 and part of exon 5), SRA behaves as a scaffold molecule that physically interacts with a number of RNA binding proteins and transcription factors via specific and critical secondary RNA structures [1–4,9].
Ligand-induced expansion of the S1′ site in the anthrax toxin lethal factor
The toxin produced and secreted by Bacillus anthracis consists of three proteins: protective antigen (PA), edema factor (EF), and lethal factor (LF). Functioning as binary toxins, PA and EF are together known as edema toxin, whereas PA and LF are known as lethal toxin. In both of these systems, PA plays an essential role to assist the entry of the partner toxin component into the target cells [1]. As a zinc metalloproteinase, LF is known to cleave the proline-rich N-terminal portion of mitogen-activated protein kinase kinases (MAPKKs) in macrophages, leading to direct impairment of the host immune system.
GDNF–Ret signaling in midbrain dopaminergic neurons and its implication for Parkinson disease
Glial cell line-derived neurotrophic factor (GDNF) and its canonical receptor Ret can signal together or independently to fulfill many important functions in the midbrain dopaminergic (DA) system. While Ret signaling clearly impacts on the development, maintenance and regeneration of the mesostriatal DA system, the physiological functions of GDNF for the DA system are still unclear. Nevertheless, GDNF is still considered to be an excellent candidate to protect and/or regenerate the mesostriatal DA system in Parkinson disease (PD).
New insights into in vitro amyloidogenic properties of human serum albumin suggest considerations for therapeutic precautions
Protein mis-folding results in many human diseases some of which are caused when it leads to amyloid aggregate formation and deposition [1,2]. Amyloids are insoluble, fibrous and well organized protein aggregates having a largely cross-β core structure [1,3]. Some examples of amyloid associated diseases include: Alzheimer’s disease, Prion disease, and Huntington’s disease, where Aβ42 peptide, PrPC protein and mutant huntingtin proteins, are respectively found to be amyloid aggregated and deposited in nervous system [1].
Structural basis for an atypical active site of an -aspartate/glutamate-specific racemase from
d-Amino acids play significant physiological roles despite their rare occurrence in nature. In human plasma, free d-serine, d-alanine, and d-proline have been reported [1]. Interestingly, d-serine in mouse and rat brains was identified as a mediator or transmitter in the nervous system [2–4]. In bacteria, d-amino acids such as d-glutamic acid and d-alanine are building blocks of the peptidoglycan layer, an essential component of the bacterial cell wall that determines cell morphology and provides resistance to osmotic rupture [5].
Role of arginine and lysine in the antimicrobial mechanism of histone-derived antimicrobial peptides
Bacterial resistance to antimicrobial drugs has become stronger, but there have been few recent advances in antimicrobials that combat this resistance [1–5]. Antimicrobial peptides (AMPs) are effective antibacterial agents, which also can have antiviral, antifungal and antitumor activities [1,2]. Many antimicrobial peptides use a lytic mechanism, disrupting the bacterial membrane [2–6]. However, other AMPs act by translocating through the membrane and affecting intracellular processes [7–10]. These translocating antimicrobial peptides may be particularly apt to avoid antimicrobial resistance [3–5].
MiR-30a attenuates immunosuppressive functions of IL-1β-elicited mesenchymal stem cells via targeting TAB3
Preeclampsia (PE), characterized by hypertension and proteinuria after 20weeks of gestation, is among the leading complications during pregnancy [1,2]. Importantly, the immune system has been revealed to be unbalanced in the maternal–fetal interface of PE subjects with the manifestation of elevated levels of pro-inflammatory cytokines, neutrophil activation and endothelial dysfunction [3,4].
GroEL to DnaK chaperone network behind the stability modulation of σ at physiological temperature in
Accurate maintenance of cellular proteome integrity is the prime criteria for survival of every cell; otherwise, aggregation of proteins causes many harmful diseases [1,2]. Significant numbers of proteins acquire their three-dimensional structure according to the Anfinsen’s model [3,4]. Others (20–30%) need co- and/or post-translational help of chaperones to acquire their biologically functional conformation [5,6]. Such chaperones were initially identified in cells under heat stress. Heat stress induces not only chaperones, but also proteases and other accessory proteins.