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FEBS Letters

A Susann Gauernack, Christian Lassek, Linlin Hou, Julia Dzieciolowski, Elena Evguenieva-Hackenberg, Gabriele Klug
The archaeal exosome, a protein complex responsible for phosphorolytic degradation and tailing of RNA, has an RNA-binding platform containing Rrp4, Csl4 and DnaG. Aiming to detect novel interaction partners of the exosome, we co-purified Nop5, which is a part of an rRNA methylating ribonucleoprotein complex, with the exosome of S. solfataricus grown to a late stationary phase. We demonstrated the capability of Nop5 to bind to the exosome with a homotrimeric Rrp4-cap and to increase the proportion of polyadenylated RNA in vitro, suggesting that Nop5 is a dual-function protein...
November 21, 2017: FEBS Letters
Shu Jia, Yusha Wang, Zhiyuan You, Bo Liu, Jinfeng Gao, Wei Liu
Accumulating evidence has indicated a role for autophagy-related (Atgs) proteins in cell regulation which is independent of their autophagic activities. As the only known transmembrane protein essential for autophagy, Atg9 cycles between the trans-Golgi network (TGN) and endosomes. Here, we report a function for mammalian Atg9 (mAtg9) in the transport of lysosomal hydrolases which impacts the lysosomal degradation capacity. Depletion of mAtg9 inhibits the degradation of EGFR and the maturation of cathepsin D and cathepsin L...
November 20, 2017: FEBS Letters
Masaki Kobayashi, Kanae Takeda, Takumi Narita, Keita Nagai, Naoyuki Okita, Yuka Sudo, Yuri Miura, Hiroki Tsumoto, Yoshimi Nakagawa, Hitoshi Shimano, Yoshikazu Higami
Sirtuin-3 (SIRT3) regulates mitochondrial quality and is involved in the anti-aging and pro-longevity actions of caloric restriction (CR). Here, we show that CR upregulates the mature form of SIRT3 and mitochondrial intermediate peptidase (MIPEP), a mitochondrial signal peptidase (MtSPase), in white adipose tissue. We also demonstrate that upregulation of mature SIRT3 is dependent on MIPEP in 3T3-L1 cells, suggesting that MIPEP may contribute to the maintenance of mitochondrial quality during CR via activation of SIRT3...
November 19, 2017: FEBS Letters
Dmitry V Sverchinsky, Vladimir F Lazarev, Pavel I Semenyuk, Vladimir A Mitkevich, Irina V Guzhova, Boris A Margulis
Most Hsp70 chaperone inhibitors exert anti-cancer effects; however, their high cytotoxicity prompted us here to employ peptide fragments of the chaperone as safer modulators of its activity and as complements to customary drugs. One such peptide, ICit-2, was found to inhibit substrate-binding and refolding activities of the chaperone. Using various approaches, we established that ICit-2 binds Hsp70, which may explain its inhibitory action. ICit-2 penetrates A-431 cancer cells and, in combination with doxorubicin, enhances the cytotoxicity and growth inhibitory effect of the drug...
November 15, 2017: FEBS Letters
Yoshihiro Tsuchiya, Keiko Osaki, Mayu Kanamoto, Yuki Nakao, Ena Takahashi, Toru Higuchi, Hideaki Kamata
PP2A is composed of a scaffolding subunit (A), a catalytic subunit (C), and a regulatory subunit (B) that is classified into four families including B, B', B'', and B'''/striatin. Here, we found that a distinct PP2A complex regulates NF-κB signaling by dephosphorylation of IKKβ, IκBα, and RelA/p65. The PP2A core enzyme AC dimer and the holoenzyme AB'''C trimer dephosphorylate IKKβ, IκBα, and RelA, whereas the ABC trimer dephosphorylates IκBα but not IKKβ and RelA in cells. In contrast, AB'C and AB''C trimers have little effect on dephosphorylation of these signaling proteins...
November 15, 2017: FEBS Letters
Rikuto Ishiguro, Nobukiyo Tanaka, Koichi Abe, Masahiro Nakajima, Takuma Maeda, Akimasa Miyanaga, Yuta Takahashi, Naohisa Sugimoto, Hiroyuki Nakai, Hayao Taguchi
BT_3567 protein, a putative β-glucosidase from Bacteroides thetaiotaomicron, exhibits higher activity towards Sop3-5 (Sopn , n: degree of polymerization of β-1,2-glucooligosaccharides) than towards Sop2 , unlike a known β-glucosidase from Listeria innocua which predominantly prefers Sop2 . In the complex structure determined by soaking of a D286N mutant crystal with Sop4 , a Sop3 moiety was observed at subsites -1 to +2. The glucose moiety at subsite +2 forms a hydrogen bond with Asn81, which is replaced with Gly in the L...
November 13, 2017: FEBS Letters
Citlali Vázquez, Marlen Mejía-Tlachi, Zabdi González-Chávez, Aketzalli Silva, José Salud Rodríguez-Zavala, Rafael Moreno-Sánchez, Emma Saavedra
Buthionine sulfoximine (BSO) induces decreased GSH and trypanothione [T(SH)2 ] pools in trypanosomatids, presumably because only gamma-glutamylcysteine synthetase (γECS) is blocked. However, some BSO effects cannot be explained by exclusive γECS inhibition; therefore, its effect on the T(SH)2 -metabolism pathway in Trypanosoma cruzi was re-examined. Parasites exposed to BSO did not synthesize T(SH)2 even when supplemented with cysteine or glutathione, suggesting trypanothione synthetase (TryS) inhibition by BSO...
November 11, 2017: FEBS Letters
Yoichiro Abe, Wakami Goda, Hiroko Ikeshima-Kataoka, Masato Yasui
Aquaporin-4, a predominant water channel in the central nervous system, has two isoforms, M1 and M23, whose transcripts are driven by distinct promoters. Using a reporter assay, we found that a fragment located between exons 0 and 1 of the mouse aquaporin-4 gene, which had been thought to be the promoter for M23, lacked enhancers functioning in astrocytes. When the astrocyte-specific enhancer (ASE) of the M1 promoter is connected to the putative M23 core promoter, it also works in astrocytes. Importantly, the ASE inhibits downstream promoter activity in NIH 3T3 cells, indicating that the ASE also functions as a silencer in cells lacking aquaporin-4...
November 10, 2017: FEBS Letters
Rabih Darwiche, Ola El Atab, Stéphanie Cottier, Roger Schneiter
In their natural habitat, yeast cells are constantly challenged by changing environmental conditions and a fierce competition for limiting resources. To thrive under such conditions, cells need to adapt and divide quickly, and be able to neutralize the toxic compounds secreted by their neighbors. Proteins like the pathogen-related yeast, Pry proteins, which belong to the large CAP/SCP/TAPS superfamily, may have an important role in this function. CAP proteins are conserved from yeast to man and are characterized by a unique αβα sandwich fold...
November 10, 2017: FEBS Letters
Robert Beattie, Simon Hippenmeyer
The mammalian cerebral cortex is responsible for higher cognitive functions such as perception, consciousness, and acquiring and processing information. The neocortex is organized into six distinct laminae, each composed of a rich diversity of cell types which assemble into highly complex cortical circuits. Radial glia progenitors (RGPs) are responsible for producing all neocortical neurons and certain glia lineages. Here, we discuss recent discoveries emerging from clonal lineage analysis at the single RGP cell level that provide us with an inaugural quantitative framework of RGP lineage progression...
November 9, 2017: FEBS Letters
Goce Taleski, Estelle Sontag
The neuronal microtubule-associated protein tau serves a critical role in regulating axonal microtubule dynamics to support neuronal and synaptic functions. Furthermore, it contributes to glutamatergic regulation and synaptic plasticity. Emerging evidence also suggests that tau serves as a signaling scaffold. Tau function and subcellular localisation are tightly regulated, in part, by the orchestrated interplay between phosphorylation and dephosphorylation events. Significantly, protein phosphatase type 2A (PP2A), encompassing the regulatory PPP2R2A (or Bα) subunit, is a major brain heterotrimeric enzyme and the primary tau Ser/Thr phosphatase in vivo...
November 9, 2017: FEBS Letters
Shotaro Otsuka, Jan Ellenberg
The nuclear pore complex (NPC) mediates all macromolecular transport across the nuclear envelope. In higher eukaryotes that have an open mitosis, NPCs assemble at two points in the cell-cycle: during nuclear assembly in late mitosis and during nuclear growth in interphase. How the NPC, the largest non-polymeric protein complex in eukaryotic cells, self-assembles inside cells remained unclear. Recent studies have started to uncover the assembly process, and evidence has been accumulating that postmitotic and interphase NPC assembly use fundamentally different mechanisms; the duration, structural intermediates, and regulation by molecular players are different and different types of membrane deformation are involved...
November 8, 2017: FEBS Letters
Norito Tamura, Taki Nishimura, Yuriko Sakamaki, Ikuko Koyama-Honda, Hayashi Yamamoto, Noboru Mizushima
ATG2 is one of the autophagy-related (ATG) proteins essential for autophagosome formation and localizes to isolation membranes and lipid droplets in mammalian cells. Here, we investigated the requirement of regions in ATG2A for its organellar localization and function. The N-terminal amino acids 1-198 and the C-terminal amino acids 1830-1938 are required for the localization to isolation membranes and lipid droplets, respectively. The C-terminal region is not required for the localization to isolation membranes and for autophagy...
November 7, 2017: FEBS Letters
Tiina Sedman, Natalja Garber, Ilja Gaidutšik, Sirelin Sillamaa, Joosep Paats, Vlad-J Piljukov, Juhan Sedman
Irc3 is a superfamily II helicase required for mitochondrial DNA stability in Saccharomyces cerevisiae. Irc3 remodels branched DNA structures, including substrates without extensive single-stranded regions. Therefore, it is unlikely that Irc3 uses the conventional single-stranded DNA translocase mechanism utilized by most helicases. Here we demonstrate that Irc3 disrupts partially triple-stranded DNA structures in an ATP-dependent manner. Our kinetic experiments indicate that the rate of ATP hydrolysis by Irc3 is dependent on the length of the double-stranded DNA cosubstrate...
November 7, 2017: FEBS Letters
Eric T Fedosejevs, Leo N C Liu, Megan Abergel, Yi-Min She, William C Plaxton
The sucrose synthase (SUS) interactome of developing castor oilseeds (COS; Ricinus communis) was assessed using coimmunoprecipitation (co-IP) with anti-(COS RcSUS1)-IgG followed by proteomic analysis. A 41-kDa polypeptide (p41) that coimmunoprecipitated with RcSUS1 from COS extracts was identified as reversibly glycosylated polypeptide-1 (RcRGP1) by LC-MS/MS and anti-RcRGP1 immunoblotting. Reciprocal Far-Western immunodot blotting corroborated the specific interaction between RcSUS1 and RcRGP1. Co-IP using anti-(COS RcSUS1)-IgG and clarified extracts from other developing seeds as well as cluster (proteoid) roots of white lupin and harsh hakea consistently recovered 90 kDa SUS polypeptides along with p41/RGP as a SUS-interactor...
November 7, 2017: FEBS Letters
O Rauh, U P Hansen, S Mach, A J W Hartel, K L Shepard, G Thiel, I Schroeder
Lipid bilayers provide many benefits for ion channel recordings, such as control of membrane composition and transport molecules. However, they suffer from high membrane capacitance limiting the bandwidth and impeding analysis of fast gating. This can be overcome by fitting the deviations of the open channel noise from the baseline noise by extended beta distributions. We demonstrate this analysis step-by-step by applying it to the example of viral K(+)  channels (Kcv), from the choice of the gating model through the fitting process, validation of the results, and what kinds of results can be obtained...
November 6, 2017: FEBS Letters
Rhoda Stefanatos, Alberto Sanz
The brain is the most complex human organ, consuming more energy than any other tissue in proportion to its size. It relies heavily on mitochondria to produce energy and is made up of mitotic and post mitotic cells that need to closely coordinate their metabolism to maintain essential bodily functions. During aging, damaged mitochondria that produce less ATP and more reactive oxygen species (ROS) accumulate. The current consensus is that ROS cause oxidative stress, damaging mitochondria and resulting in an energetic crisis that triggers neurodegenerative diseases and accelerates aging...
November 6, 2017: FEBS Letters
Kwon Joo Yeo, Jun-Goo Jee, Eunha Hwang, Eun-Hee Kim, Young Ho Jeon, Hae-Kap Cheong
Interaction between angiogenin and the p53 TAD2 domain in cancer cells can inhibit the function of the p53 tumor suppressor and promote cell survival. Based on a model structure using NMR and mutational analysis, positively charged (31) RRR(33) and (50) KRSIK(54) motifs of human angiogenin were identified as p53 binding sites that could interact with negatively charged D48/E51 and E56 residues of the p53 TAD2 domain, respectively. These results suggest that (31) RRR(33) and (50) KRSIK(54) motifs of human angiogenin might play a critical role in the regulation of p53-mediated apoptosis and angiogenesis in cancer cells...
November 6, 2017: FEBS Letters
Yohei Kanamori, Masaru Murakami, Tohru Matsui, Masayuki Funaba
Hepcidin plays a central role in systemic iron metabolism. The bone morphogenetic protein (BMP) pathway regulates expression of hepcidin through transcriptional activation via BMP-responsive elements (REs) 1 and 2 on the promoter. Previous studies also revealed that the BMP pathway stimulates transcription of its target genes via GC-rich sequences on the promoter. A search for GC-rich sequences on the hepcidin promoter indicated 13 regions across the distal (A to F), middle (G to I) and proximal (J to M) areas; among them, mutations of the GC-rich element found in regions B to D exhibited decreased responsiveness to ALK3(QD) expression in the presence of BMP-RE1 mutations, indicating necessity of the elements for full expression of hepcidin by the BMP pathway...
November 4, 2017: FEBS Letters
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