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FEBS Letters

Daniela Ruffell
To understand the significance of this ruling, we need to look at the history behind it. The directive defines a GMO (Genetically Modified Organism) being "an organism […], in which the genetic material has been altered in a way that does not occur naturally by mating and/or natural recombination". Such alterations may include the addition of foreign genetic material (transgenesis), or the mutation or deletion of an autochthonous gene. This article is protected by copyright. All rights reserved.
November 13, 2018: FEBS Letters
M V Selvadurai, R J Brazilek, M J Moon, J-Y Rinckel, A Eckly, C Gachet, P J Meikle, H H Nandurkar, W S Nesbitt, J R Hamilton
PI3KC2α is a phosphoinositide 3-kinase with a recently reported function in platelets; PI3KC2α-deficient mouse platelets have altered membrane structure and impaired function. Yet, how these membrane changes cause platelet dysfunction remains unknown. Here, focused ion beam-scanning electron microscopy of PI3KC2α-deficient platelet ultrastructure reveals a specific effect on the internal membrane structure, while liquid chromatography-tandem mass spectrometry profiling of 294 lipid species shows unaltered lipid composition...
November 12, 2018: FEBS Letters
Swagatika Sahoo, R Ranjith Kumar, Brandon Nicolay, Omkar Mohite, Karthikeyan Sivaraman, Vikas Khetan, Pukhraj Rishi, Suganeswari Ganesan, Krishnakumar Subramanian, Karthik Raman, Wayne Miles, Sailaja V Elchuri
Retinoblastoma (RB) is a childhood eye cancer. Currently chemotherapy, local therapy and enucleation are the main ways in which these tumors are managed. The present work is the first study that uses constraint-based reconstruction and analysis approaches to identify and explain RB-specific survival strategies, which are RB tumor-specific. Importantly, our model-specific secretion profile is also found in RB1-depleted human retinal cells in vitro and suggest that novel biomarkers involved in lipid metabolism may be important...
November 11, 2018: FEBS Letters
Qingkun Dong, Zhiwei Zhang, Yuting Liu, Li-Zhen Tao, Huili Liu
The Arabidopsis FERONIA (FER) receptor kinase is a key hub of cell signaling networks mediating various hormone, stress, and immune responses. Previous studies have shown that FER functions correlate with auxin responses, but the underlying molecular mechanism is unknown. Here, we demonstrate that the primary root of the fer-4 mutant displays increased lateral root branching and a delayed gravitropic response, which are associated with polar auxin transport (PAT). Our data suggest that aberrant PIN2 polarity is responsible for the delayed gravitropic response in fer-4...
November 11, 2018: FEBS Letters
Ping Wang, Han Bao, Xiao-Peng Zhang, Feng Liu, Wei Wang
The acetylation of p53 plays an essential role in regulating its transcriptional activity. Nevertheless, how p53 acetylation is modulated in cell fate decision is less understood. We developed a network model to reveal how Tip60-dependent p53 acetylation is regulated to modulate cellular outcome. We proposed that p53 is progressively activated and exhibits distinct dynamics depending on the severity of DNA damage. For mild damage, p53 is primarily activated to trigger cell cycle arrest by transactivating p21, with its concentration showing pulses...
November 10, 2018: FEBS Letters
Natasha E Zachara
Almost 100 years after the first descriptions of proteins conjugated to carbohydrates (mucins), several studies suggested that glycoproteins were not restricted to the serum, extracellular matrix, cell surface, or endomembrane system. In the 1980's, key data emerged demonstrating that intracellular proteins were modified by monosaccharides of O-linked β-N-acetylglucosamine (O-GlcNAc). Subsequently, this modification was identified on thousands of proteins that regulate cellular processes as diverse as protein aggregation, localization, post-translational modifications, activity, and interactions...
November 9, 2018: FEBS Letters
Qin Zhu, Wei Guo, Shengjie Zhang, Yang Feng, Xiao Wang, Libing Zhou, Guo-Ru Huang
Procollagen processing is essential for organ development and tissue functions. Both procollagen C-proteinase enhancer 1 (PCPE1) and secreted frizzled-related protein 2 (sFRP2) play vital roles in collagen formation via regulating the procollagen C-proteinase (pCP) activity of bone morphogenetic protein 1 (BMP1). However, whether the two proteins exert a synergistic effect on BMP1 activity remains unclear. Here, simultaneous knockdown of sFRP2 and PCPE1 led to less collagen formation in mouse embryonic fibroblasts and dorsalized phenotypes in zebrafish embryos...
November 9, 2018: FEBS Letters
James S Davies, David Coombes, Christopher R Horne, F Grant Pearce, Rosmarie Friemann, Rachel A North, Renwick C J Dobson
N-Acetylglucosamine-6-phosphate deacetylase (NagA) and glucosamine-6-phosphate deaminase (NagB) are branch point enzymes that direct amino sugars into different pathways. For Staphylococcus aureus NagA, analytical ultracentrifugation and small-angle X-ray scattering data demonstrate that it is an asymmetric dimer in solution. Initial rate experiments show hysteresis, which may be related to pathway regulation, and kinetic parameters similar to other bacterial isozymes. The enzyme binds two Zn2+ ions and is not substrate inhibited, unlike the Escherichia coli isozyme...
November 9, 2018: FEBS Letters
Jacquelyn LaVallee, Terrain Grant, Stephanie D'Angelo-Early, Sergey Kletsov, Nicole A Berry, Kimberly M Abt, Christopher P Bloch, Mario L Muscedere, Kenneth W Adams
NAB1 and 2 are coregulators for early growth response (Egr) transcription factors. The NAB1 nuclear localization signal (NLS) was previously described as a bipartite NLS of sequence R(X2 )K(X11 )KRXK. The sequence is conserved in NAB2 as K(X2 )R(X11 )KKXK, however, whether it functions as the NAB2 NLS has not been tested. We show that the KKXK motif in NAB2 is necessary and sufficient to mediate nuclear localization. Mutation of the KKXK motif to AAXA causes cytoplasmic localization of NAB2, while Lys/Arg-to-Ala mutations of the upstream K(X2 )R motif have no effect...
November 9, 2018: FEBS Letters
Simin Zheng, Anthony Kusnadi, Jee Eun Choi, Bao Q Vuong, Daniela Rhodes, Jayanta Chaudhuri
Class switch recombination (CSR) in B cells involves deletion-recombination at switch (S) region DNA and is important for the diversification of antibody isotypes during an immune response. Here, we identify two NME [NM23/NDPK (nucleoside diphosphate kinase)] isoforms, NME1 and NME2, as novel players in this process. Knockdown of NME2 leads to decreased CSR, while knockdown of the highly homologous NME1 results in increased CSR. Interestingly, these NME proteins also display differential occupancy at S regions during CSR despite their homology; NME1 binds to S regions prior to stimulation while NME2 binds to S regions only after stimulation...
November 9, 2018: FEBS Letters
Francesca Salvi, Malgorzata Trebacz, Thomas Kokot, Bernhard Hörmann, Pablo Rios, Orsolya Barabas, Maja Kӧhn
Protein phosphatase-1 (PP1) drives a large amount of phosphoSer/Thr protein dephosphorylations in eukaryotes to counteract multiple kinases in signalling pathways. The phosphatase requires divalent metal cations for catalytic activity and contains iron naturally. Iron has been suggested to have an influence on PP1 activity through Fe2+ and Fe3+ oxidation states. However, much biochemical and all structural data have been obtained with recombinant PP1 containing Mn2+ ions. Purifying iron-containing PP1 from E...
November 7, 2018: FEBS Letters
Makiko Sakka, Emi Kunitake, Tetsuya Kimura, Kazuo Sakka
Laminin_G_3 modules can exist together with family-43 catalytic modules of glycoside hydrolase (GH43), but their functions are unknown. Here, a laminin_G_3 module and a GH43 module derived from a Ruminiclostridium josui modular arabinofuranosidase Abf43A-Abf43B-Abf43C were produced individually as RjLG3 and RjGH43_22, respectively, or combined as RjGH43-1 to gain insights into their activities. Isothermal calorimetry analysis showed that RjLG3 has high affinity toward 32 -α-L-arabinofuranosyl-(1,5)-α-L-arabinotriose but not for α-1,5-linked arabinooligosaccharides, which suggests that RjLG3 interacts specifically with a branched arabinofuranosyl residue of an arabinooligosaccharide but not an arabinofuranosyl residue at the end of α-1,5-linked arabinooligosaccharides...
November 7, 2018: FEBS Letters
José P Leite, Luís Gales
The interaction of the amyloid-β peptide (Aβ) with thermolysin (TLN) was investigated by X-ray crystallography. Structural models of the complexes of TLN with several Aβ fragments show that, despite the numerous possible cleavage sites of the Aβ sequence, the C-terminal product of Ala30-Ile31 cleavage does not dissociate, thus inhibiting the enzyme. The high similarity between the TLN structural motif and neprilysin (NEP), the most extensively studied peptidase associated with Aβ clearance, suggests that NEP should be more efficient against Aβ polymorphs where Ala30-Ile31 is inaccessible, which is in agreement with studies in living mice that point to the limited role of NEP in degrading soluble Aβ and its higher ability to degrade insoluble and/or oligomeric Aβ forms, producing only the Aβ10-37 intermediate...
November 7, 2018: FEBS Letters
Chengliang Wang, Li Zhan, Minhao Wu, Rongsheng Ma, Jun Yao, Ying Xiong, Yang Pan, Shenheng Guan, Xuan Zhang, Jianye Zang
Using methods combining cross-linking, pull-down assays, and stable isotope labelling by amino acids in cell culture with mass spectrometry, we identified that the Tudor domain-containing protein Spindlin-1 recognizes trimethylation of histone H4 lysine 20 (H4K20me3). The binding affinity of Spindlin-1 to H4K20me3 is weaker than that to H3K4me3, indicating H4K20me3 as a secondary substrate for Spindlin-1. Structural studies of Spindlin-1 in complex with the H4K20me3 peptide indicate that Spindlin-1 attains a distinct binding mode for H4K20me3 recognition...
November 1, 2018: FEBS Letters
Yawei Han, Kun Zhang, Yuheng Hong, Jingzhao Wang, Qi Liu, Zhen Zhang, Han Xia, Yutao Tang, Tengshuai Li, Liandong Li, Yuan Xue, Wei Hong
Through their multiple targets, microRNAs (miRNAs) are involved in numerous physiological and pathological processes. In this study, miR-342-3p was found to be deregulated with ossification of ligament or osteoporosis. We demonstrate that silencing miR-342-3p impairs osteoblast activity and matrix mineralization, while over-expression of miR-342-3p promotes osteoblast differentiation significantly. Moreover, miR-342-3p directly targets activating transcription factor 3 (ATF3), which inhibits transcription of pro-osteogenic differentiation-associated genes...
November 1, 2018: FEBS Letters
Xiaodong Chi, Yunqing Chang, Mengmiao Li, Jin Lin, Yi Liu, Chuanyou Li, Shenjie Tang, Junjie Zhang
Toxin-antitoxin (TA) systems are regarded as genetic modules that facilitate bacterial survival under stress conditions. In this study, a novel TA system in M. tuberculosis H37Rv chromosome was identified, termed as mt-PemIK, which consists of antitoxin mt-PemI and toxin mt-PemK (Rv3098A). Induction of mt-PemK leads to growth arrest in M. smegmatis, while the toxic effect of mt-PemK is eliminated by co-expression of mt-PemI. mt-PemK is characterized as an endoribonuclease whose activity is pH-dependent. mt-PemK, as well as some other M...
October 29, 2018: FEBS Letters
Kenji Fukui, Akiko Harada, Taisuke Wakamatsu, Ai Minobe, Koki Ohshita, Makoto Ashiuchi, Takato Yano
In plant organelle genomes, homeologous recombination between heteroallelic positions of repetitive sequences is increased by dysfunction of the gene encoding MutS homolog 1 (MSH1), a plant organelle-specific homolog of bacterial mismatch-binding protein MutS1. The C-terminal region of plant MSH1 contains the GIY-YIG endonuclease motif. The biochemical characteristics of plant MSH1 have not been investigated; accordingly, the molecular mechanism by which plant MSH1 suppresses homeologous recombination is unknown...
October 29, 2018: FEBS Letters
A Zare, A M Johansson, E Karlsson, N Delhomme, P Stenberg
Environmental perturbations induce transcriptional changes, some of which may be inherited even in the absence of the initial stimulus. Previous studies have focused on transfers through the germ-line although microbiota is also passed on to the offspring. Thus, we inspected the involvement of the gut microbiome in transgenerational inheritance of environmental exposures in Drosophila melanogaster. We grew flies in the cold versus control temperatures and compared their transcriptional patterns in both conditions as well as in their offspring...
October 29, 2018: FEBS Letters
Zachary A McDargh, Anirban Polley, Ben O'Shaughnessy
SNARE proteins constitute the core of the exocytotic membrane fusion machinery. Fusion occurs when vesicle-associated and target membrane-associated SNAREs zipper into trans-SNARE complexes ('SNAREpins'), but the number required is controversial and the mechanism of cooperative fusion is poorly understood. We developed a highly coarse-grained molecular dynamics simulation to access the long fusion timescales, which revealed a two-stage process. First, zippering energy was dissipated and cooperative entropic forces assembled the SNAREpins into a ring; second, entropic forces expanded the ring, pressing membranes together and catalyzing fusion...
October 22, 2018: FEBS Letters
Masami Nakazawa, Hiroko Ando, Ayusa Nishimoto, Tsuyoshi Ohta, Kimitoshi Sakamoto, Takahiro Ishikawa, Mitsuhiro Ueda, Tatsuji Sakamoto, Yoshihisa Nakano, Kazutaka Miyatake, Hiroshi Inui
In Euglena gracilis, wax ester fermentation produces ATP during anaerobiosis. Here, we report that anaerobic wax ester production is suppressed when the mitochondrial electron transport chain complex I is inhibited by rotenone, whereas it is increased by the uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP). The ADP/ATP ratio in anaerobic cells is elevated by treatment with either rotenone or CCCP. Gene silencing experiments indicate that acyl-CoA dehydrogenase, electron transfer flavoprotein (ETF), and rhodoquinone (RQ) participate in wax ester production...
October 16, 2018: FEBS Letters
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