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FEBS Letters

Marilyn Carrier, Regis Lutzing, Samia Gaouar, Cécile Rochette-Egly
The nuclear retinoic acid (RA) receptors (RARα, β and γ) are ligand-dependent regulators of transcription. Upon activation by RA, they are recruited at the promoters of target genes together with several coregulators. Then they are degraded by the ubiquitin proteasome system. Here we report that the degradation of the RARα subtype involves ubiquitination and the tripartite motif protein TRIM24, which was originally identified as a ligand-dependent corepressor of RARα. We show that in response to RA, TRIM24 serves as an adapter linking RARα to the proteasome for its degradation...
March 15, 2018: FEBS Letters
Jiang Dongxu, Xuan Zou, Cheng Zhang, Jincao Chen, Zhiqiang Li, Yunfu Wang, Zixin Deng, Liangrong Wang, Shi Chen
Gemin5 acts as a U1 small nuclear RNA (snRNA)-binding protein in U1 small nuclear ribonucleic protein (snRNP) biogenesis. Here, we report a role for Gemin5 in unassembled U1 snRNP disposal under survival of motor neuron (SMN) protein-deficient conditions. We demonstrate that non-Sm protein-associated U1 snRNA and U1A are enriched in cytoplasmic granules and co-localize to P bodies in SMN-deficient cells. Immunoprecipitation assays show increased associations of the U1 snRNP component U1A with P body components and Gemin5 in SMN-deficient cells...
March 14, 2018: FEBS Letters
Poorna Manasa Bhamidimarri, Lakshmi Surekha Krishnapati, Surendra Ghaskadbi, Siva Kumar Nadimpalli
Mannose 6-phosphate (M6P)-dependent lysosomal enzyme targeting to endosome/lysosome complex is poorly understood among lower invertebrates. So far, only a M6P-independent lysosomal enzyme sorting protein, named LERP, has been described in Drosophila. Here, we have identified mannose 6-phosphate receptor (MPR) homologues in Hydra vulgaris, a basal Cnidarian, at genome level and further purified a cation-dependent MPR (CDMPR)-like protein from hydra using affinity chromatography. Structural comparisons of hydra MPRs with mammalian MPRs confirm that the residues important for interacting with the M6P ligand are conserved...
March 14, 2018: FEBS Letters
Rhesa Budhidarmo, Jingyi Zhu, Adam J Middleton, Catherine L Day
The Really Interesting New Gene (RING) Finger protein 11 (RNF11) is a subunit of the A20- ubiquitin-editing complex that ensures the transient nature of inflammatory responses. Although the role of RNF11 as a negative regulator of NF-κB signalling is well documented, the molecular mechanisms that underpin this function are poorly understood. Here, we show that RNF11 binds both Ubc13 and the Ubc13~ubiquitin conjugate tightly and with similar affinity, but has minimal E3 ligase activity. Remarkably, RNF11 appears to bind Ubc13 so tightly that it out-competes the E1 and an active E3 ligase...
March 14, 2018: FEBS Letters
Sofía Ruiz-Cruz, Ana Moreno-Blanco, Manuel Espinosa, Alicia Bravo
Global transcriptional regulators play key roles during bacterial adaptation to environmental fluctuations. Protein MafR from Enterococcus faecalis was shown to activate the transcription of many genes on a genome-wide scale. We proposed that MafR is a global regulator of the Mga/AtxA family. Here, we purified an untagged form of the MafR protein and found that it binds to linear double-stranded DNAs in a non-sequence-specific manner. Moreover, multiple MafR units (likely dimers) bind sequentially to the DNA molecule generating multimeric complexes...
March 14, 2018: FEBS Letters
Go Sakai, Haruhiko Tokuda, Naohiro Yamamoto, Rie Matsushima-Nishiwaki, Kazuhiko Fujita, Tetsu Kawabata, Osamu Kozawa, Takanobu Otsuka
Heat shock protein 22 (HSP22) is ubiquitously expressed in various types of cells including in osteoblasts. We previously reported that TNF-α stimulates interleukin (IL)-6 synthesis via p44/p42 MAPK in osteoblast-like MC3T3-E1 cells and that mTOR/p70 S6 kinase (p70 S6K) negatively regulates the IL-6 synthesis. In the present study, we investigated the involvement of HSP22 in TNF-α-stimulated-IL-6 synthesis and the underlying mechanism in MC3T3-E1 cells. HSP22 knockdown reduces TNF-α-stimulated release of IL-6...
March 12, 2018: FEBS Letters
Timothy Chen, Kapil Dave, Martin Gruebele
In-cell protein stability is increased by crowding, but can be reduced by destabilizing surface interactions. Will different denaturation techniques yield similar trends? Here, we apply pressure and thermal denaturation to GFP/ReAsH-labeled yeast phosphoglycerate kinase (PGK) in E. coli cells. Pressure denaturation is more two state-like in E. coli than in vitro, stabilizing the native state. Thermal denaturation destabilizes PGK in E. coli, unlike in mammalian cells. Results in wild-type MG1655 strain are corroborated in pressure-resistant J1 strain, where PGK is less prone to aggregation...
March 9, 2018: FEBS Letters
Nancy B Schwartz, Miriam S Domowicz
Proteoglycans are diverse, complex extracellular/cell surface macromolecules composed of a central core protein with covalently-linked glycosaminoglycan (GAG) chains; both of these components contribute to the growing list of important bio-active functions attributed to proteoglycans. Increasingly, attention has been paid to the roles of proteoglycans in nervous tissue development due to their highly regulated spatio/temporal expression patterns, whereby they promote/inhibit neurite outgrowth, participate in specification and maturation of various precursor cell types, and regulate cell behaviors like migration, axonal pathfinding, synaptogenesis, and plasticity...
March 7, 2018: FEBS Letters
Wanwen Lan, Aihua Hou, Rajamani Lakshminarayanan, Yoon-Pin Lim, Louis Tong
Long intergenic non-coding RNAs (lincRNAs) are not fully characterized in disease, although many are involved in controlling differentiation. We discovered and sequenced a novel 4.4 kb human lincRNA called linc-9432 in pterygium, an ocular disease characterized by a wedge lesion. This transcript inhibited differentiation-induced cell death, promoted expression of stem cell markers, and decreased expression of epithelial and mesenchymal differentiation markers. This lincRNA regulated 30 differentiation-related genes in transcriptome analysis and 17/30 gene products were known to be directly associated in a network...
March 7, 2018: FEBS Letters
Shuping Zheng, Ying Zhou, Joy Fleming, Yafeng Zhou, Mengting Zhang, Shiliang Li, Honglin Li, Bingqi Sun, Wei Liu, Lijun Bi
Mycobacterium tuberculosis is a notorious pathogen that continues to threaten human health. Rv0164, an antigen of both T- and B-cells conserved across mycobacteria, and MSMEG_0129, its close homolog in Mycobacterium smegmatis, are predicted members of the START domain superfamily, but their molecular function is unknown. Here, gene knockout studies demonstrate MSMEG_0129 is essential for bacterial growth, suggesting Rv0164 may be a potential drug target. The MSMEG_0129 crystal structure determined at 1.95 Å reveals a fold similar to that in polyketide aromatase/cyclases ZhuI and TcmN from Streptomyces sp...
March 7, 2018: FEBS Letters
Xiaolai Lei, Lu Wang, Guoping Zhao, Xiaoming Ding
Serine integrases mediate site-specific recombination and are extensively applied in genetic engineering and synthetic biology. However, which regions of the attachment sites determine site-specificity and how these regions function in recombination remain elusive. Here, we explored the sequence features of attB attachment sites recognized by ɸBT1 integrase, a representative serine integrase. A 34-bp DNA motif is found that displays distinct base-specific preference for every position. Further investigation of mutations at different positions within the attB sequence shows different recombination efficiencies and binding affinities...
March 7, 2018: FEBS Letters
Anna Niesteruk, Marie Hutchison, Sridhar Sreeramulu, Hendrik R A Jonker, Christian Richter, Rupert Abele, Christoph Bock, Harald Schwalbe
Although intrinsically disordered proteins or protein domains (IDPs or IDD) are less abundant in bacteria than in eukaryotes, their presence in pathogenic bacterial proteins is important for protein-protein interactions. The protein tyrosine kinase A (PtkA) from Mycobacterium tuberculosis possesses an 80-residue disordered region (IDDP tkA ) of unknown function, located N-terminally to the well-folded kinase core domain (KCD). Here, we characterize the conformation of IDDP tkA under varying biophysical conditions and phosphorylation using NMR-spectroscopy...
March 1, 2018: FEBS Letters
Yuzhe Zhang, Ming Lei, Xiajie Yang, Yue Feng, Yuan Yang, Peter Loppnau, Yanjun Li, Yi Yang, Jinrong Min, Yanli Liu
TIP60 consists of an N-terminal chromo barrel domain (TIP60-CB) and a C-terminal acetyltransferase domain and acetylates histone and non-histone proteins in diverse cellular processes. While TIP60-CB is thought to recognize histone tails, molecular details of this interaction remain unclear. Here, we attempted a quantitative analysis of the interaction between the human TIP60-CB and histone peptides, but did not observe any detectable binding by either fluorescence polarization or isothermal titration calorimetry assays...
March 1, 2018: FEBS Letters
Maria Papatriantafyllou
Barcelona, Catalonia, Spain. Not for a single moment should we neglect viewing the area that has lately been the focus of heated political discussions as one of the most important hubs in European Biomedical Research. The Centre for Genomic Regulation (CRG) is the beating heart of the Barcelona Biomedical Research Park (PRBB), ranking 23rd among the Western European institutes that are active in the health sector (SCIMAGO institutions rankings 2017). The CRG turns 18 this year, counting over 400 scientists from 43 countries, and features 29 research groups and 9 core facilities...
February 28, 2018: FEBS Letters
Ellen Becher, Alexander Heese, Laura Claußen, Sebastian Eisen, Nico Jehmlich, Thore Rohwerder, Jessica Purswani
In detoxification and fermentation processes, acylating dehydrogenases catalyze the reversible oxidation of aldehydes to their corresponding acyl-CoA esters. Here, we characterize an enzyme from Aquincola tertiaricarbonis L108 responsible for prenal (3-methyl-2-butenal) to 3-methylcrotonyl-CoA oxidation. Enzyme kinetics demonstrate a preference for C5 substrates not yet observed in aldehyde dehydrogenases. Compared to acetaldehyde and acetyl-CoA, conversion of valeraldehyde and valeryl-CoA is >100- and 8-fold more efficient, respectively...
February 27, 2018: FEBS Letters
Yun Li, Shen Wang, Tianzhi Li, Le Zhu, Cong Ma
As a SNARE binding protein, tomosyn has been reported to negatively regulate synaptic exocytosis via arresting syntaxin-1 and SNAP-25 into a non-fusogenic product that precludes synaptobrevin-2 entry, raising the question how the assembly of the SNARE complex is achieved. Here, we have investigated new functions of tomosyn in SNARE complex formation and SNARE-mediated vesicle fusion. Assisted by NSF/α-SNAP, syntaxin-1 escapes tomosyn arrest and assembles into the Munc18-1/syntaxin-1 complex. Munc13-1 then catalyzes the transit of syntaxin-1 from the Munc18-1/syntaxin-1 complex to the SNARE complex in a manner specific to synaptobrevin-2 but resistant to tomosyn...
February 27, 2018: FEBS Letters
Jason Shirian, Valeria Arkadash, Itay Cohen, Tamila Sapir, Evette S Radisky, Niv Papo, Julia M Shifman
MMP-14 and MMP-9 are two well established cancer targets for which no specific clinically relevant inhibitor is available. Using a powerful combination of computational design and yeast surface display technology, we engineered such an inhibitor starting from a non-specific MMP inhibitor, N-TIMP2. The engineered purified N-TIMP2 variants showed enhanced specificity towards MMP-14 and MMP-9 relative to a panel of off-target MMPs. MMP-specific N-TIMP2 sequence signatures were obtained that could be understood from the structural perspective of MMP/N-TIMP2 interactions...
February 23, 2018: FEBS Letters
Federica Centorrino, Alice Ballone, Madita Wolter, Christian Ottmann
The USP8/14-3-3 protein-protein interaction has recently been shown to exert a significant role in the pathogenesis of Cushing's disease (CD). USP8 is a deubiquitinase that prevents epidermal growth factor receptor (EGFR) degradation. Impairment of 14-3-3 binding leads to a higher deubiquitination of EGFR and results in a higher EGFR signaling and an increased production of adrenocorticotropic hormone (ACTH). Here we report the high-resolution crystal structure of the 14-3-3 binding motif of USP8 surrounding Ser718 in complex with 14-3-3ζ and characterize the interaction with fluorescence polarization and isothermal titration calorimetry...
February 23, 2018: FEBS Letters
Amandine Draime, Laure Bridoux, Magali Belpaire, Tamara Pringels, Hervé Degand, Pierre Morsomme, René Rezsohazy
HOXA1 belongs to the HOX family of transcription factors which are key regulators of animal development. Little is known about the molecular pathways controlling HOXA1. Recent data from our group revealed distinct partner proteins interacting with HOXA1. Among them, OGT is an O-linked N-acetylglucosamine (O-GlcNAc) transferase modifying a variety of proteins involved in different cellular processes including transcription. Here, we confirm OGT as a HOXA1 interactor, we characterise which domains of HOXA1 and OGT are required for the interaction, and we provide evidence that OGT post-translationally modifies HOXA1...
February 21, 2018: FEBS Letters
Sabrina Schroeder, Joshua D Kaufman, Matthias Grunwald, Peter J Walla, Nils-Alexander Lakomek, Paul T Wingfield
The HIV-1 envelope gp120/gp41 trimer mediates viral membrane fusion. After CD-4 recognition, gp120 detaches from the virus, exposing gp41 which triggers fusion. During the fusion process, gp41 may not remain trimeric, which could have functional importance. Here, we probe the reversible association of full length gp41 (minus the cytoplasmic domain) in detergent micelles (with probes attached to transmembrane domain) by fluorescence resonance energy transfer (FRET) with a μM dissociation constant. This is compared with other methods...
February 17, 2018: FEBS Letters
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