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FEBS Journal

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https://www.readbyqxmd.com/read/28317270/3q26-29-amplification-in-head-and-neck-squamous-cell-carcinoma-a-review-of-established-and-prospective-oncogenes
#1
REVIEW
Matthew A Davidson, Emma J Shanks
Head and neck cancer (HNSCC) is significantly underrepresented in worldwide cancer research, despite the fact that survival rates for the disease have remained static for over 50 years. Distant metastasis is often present at the time of diagnosis, and is the primary cause of death in cancer patients. In the absence of routine effective targeted therapies, the standard of care treatment remains chemoradiation in combination with (often disfiguring) surgery. A defining characteristic of HNSCC is the amplification of a region of chromosome 3 (3q26-29), which is consistently associated with poorer patient outcome...
March 19, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28304152/reprogramming-of-histone-methylation-controls-the-differentiation-of-monocytes-into-macrophages
#2
Qi-Fan Zheng, Hui-Min Wang, Zhan-Feng Wang, Jin-Yang Liu, Qi Zhang, Li Zhang, Yuan-Hua Lu, Han You, Guang-Hui Jin
Subset heterogeneity of the mononuclear phagocyte system (MPS) is controlled by defined transcriptional networks and programs; however, the dynamic establishment of programs that control broad, orchestrated expression of transcription factors (TFs) during the progression of monocyte-into-phagocyte (MP) differentiation remains largely unexplored. By using chromatin immunoprecipitation assays, we show the extensive trimethylation of histone H3 lysine 4 (H3K4me3) as well as histone H3 lysine 27 (H3K27me3) occupancy with broad footprints at the promoters of MP differentiation-related TFs, such as HOXA and FOXO genes, KLF4, IRF8 and others...
March 17, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28304148/the-enigmatic-role-of-runx1-in-female-related-cancers-current-knowledge-future-perspectives
#3
REVIEW
Alessandra I Riggio, Karen Blyth
Historically associated with the aetiology of human leukaemia, the RUNX1 gene has in recent years reared its head in an assortment of epithelial cancers. This review discusses the state-of-the-art knowledge of the enigmatic role played by RUNX1 in female-related cancers of the breast, the uterus and the ovary. The weight of evidence accumulated so far is indicative of a very context-dependent role, as either an oncogene or a tumour suppressor. This is corroborated by high-throughput sequencing endeavours which report different genetic alterations affecting the gene, including amplification, deep deletion and mutations...
March 17, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28296235/the-circular-rna-cirs-7-promotes-app-and-bace1-degradation-in-an-nf-%C3%AE%C2%BAb-dependent-manner
#4
Zhemin Shi, Ting Chen, Qingbin Yao, Lina Zheng, Zhen Zhang, Jingzhao Wang, Zhimei Hu, Hongmei Cui, Yawei Han, Xiaohui Han, Kun Zhang, Wei Hong
The aberrant accumulation of β-amyloid peptide (Aβ) in the brain is a key feature of Alzheimer's disease (AD), and enhanced cleavage of β-amyloid precursor protein (APP) by β-site APP-cleaving enzyme 1 (BACE1) has a major causative role in AD. Despite their prominence in AD pathogenesis, the regulation of BACE1 and APP is incompletely understood. In this study, we report that the circular RNA circular RNA sponge for miR-7 (ciRS-7) has an important role in regulating BACE1 and APP protein levels. Previous studies have shown that ciRS-7, which is highly expressed in the human brain, is down-regulated in the brain of people with AD but the relevance of this finding was not clear...
March 13, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28294556/unmodified-and-pyroglutamylated-amyloid-%C3%AE-peptides-form-hypertoxic-hetero-oligomers-of-unique-secondary-structure
#5
Greg Goldblatt, Lucia Cilenti, Jason O Matos, Briana Lee, Nicholas Ciaffone, Qing X Wang, Laurene Tetard, Ken Teter, Suren A Tatulian
Amyloid β (Aβ) peptide plays a major role in Alzheimer's disease (AD) and occurs in multiple forms, including pyroglutamylated Aβ (AβpE). Identification and characterization of the most cytotoxic Aβ species is necessary for advancement in AD diagnostics and therapeutics. While in brain tissue multiple Aβ species act in combination, structure/toxicity studies and immunotherapy trials have been focused on individual forms of Aβ. As a result, the molecular composition and the structural features of "toxic Aβ oligomers" have remained unresolved...
March 13, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28296245/immunodominant-protein-mip_05962-from-mycobacterium-indicus-pranii-displays-chaperone-activity
#6
Ashish Sharma, M A Equbal, S Pandey, Javaid A Sheikh, Nasreen Z Ehtesham, Seyed E Hasnain, Tapan K Chaudhuri
Tuberculosis, a contagious disease of infectious origin is currently a major cause of deaths worldwide. Mycobacterium indicus pranii (MIP), a saprophytic non-pathogen and a potent immunomodulator is currently being investigated as an intervention against tuberculosis along with many other diseases with positive outcome. The apparent paradox of multiple chaperones in mycobacterial species and enigma about the cellular functions of the client proteins of these chaperones need to be explored. Chaperones are the known immunomodulators thus there is need to exploit the proteome of MIP for identification and characterization of putative chaperones...
March 10, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28296196/sirt6-reduces-macrophage-foam-cell-formation-by-inducing-autophagy-and-cholesterol-efflux-under-ox-ldl-condition
#7
Jiangping He, Guangya Zhang, Qi Pang, Cong Yu, Jie Xiong, Jing Zhu, Fengling Chen
SIRT6 is a pivotal regulator of lipid metabolism. It is also closely connected to cardiovascular diseases, which are the main cause of death in diabetic patients. We observed a decrease in the expression of SIRT6 and key autophagy effectors (ATG5, LC3B, and LAMP1) in ox-LDL-induced foam cells, a special form of lipid-laden macrophages. In these cells, SIRT6 WT but not SIRT6 H133Y overexpression markedly reduced foam cell formation, as shown by Oil Red O staining, while inducing autophagy flux, as determined by both mRFP-GFP-LC3 labeling and transmission electron microscopy...
March 9, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28294537/beyond-histones-the-expanding-roles-of-protein-lysine-methylation
#8
REVIEW
Zhouran Wu, Justin Connolly, Kyle K Biggar
A robust signaling network is essential for cell survival. At the molecular level, this is often mediated by as many as 200 different types of post-translational modifications that are made to proteins. These include well-documented examples such as phosphorylation, ubiquitination, acetylation, and methylation. Of these modifications, non-histone protein lysine methylation has only recently emerged as a prevalent modification occurring on numerous proteins, thus extending its role well beyond the histone code...
March 9, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28244221/genomic-rearrangements-induced-by-unscheduled-dna-double-strand-breaks-in-somatic-mammalian-cells
#9
REVIEW
Ayeong So, Tangui Le Guen, Bernard S Lopez, Josée Guirouilh-Barbat
DNA double-strand breaks (DSBs) are highly toxic lesions that can lead to profound genome rearrangements and/or cell death. DSBs routinely occur in genomes due to endogenous or exogenous stresses. Efficient repair systems, canonical non-homologous end-joining and homologous recombination, exist in the cell and not only ensure the maintenance of genome integrity but also, via specific programmed DNA double-strand breaks, permit its diversity and plasticity. However, these repair systems need to be tightly controlled because they can also generate genomic rearrangements...
February 28, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28236666/the-epsilon-motif-of-hepatitis-b-virus-rna-exhibits-a-potassium-dependent-ribonucleolytic-activity
#10
Dibyajnan Chakraborty, Sagarmoy Ghosh
Fourteen different classes of ribozymes are known that catalyze a range of diverse chemical reactions. We report here a novel potassium-dependent nucleolytic activity present in Hepatitis B Virus (HBV) RNA. A short RNA region (53 nt) with enzymatic properties released itself from the viral sequence by cis cleavages and could subsequently act in trans. The released region encompassed the epsilon motif present in the HBV RNA. The 3' end of the liberated fragment was within the non-canonical polyadenylation signal (UAUAAA) of the viral RNA while cleavages at about 53 nt upstream sites released the fragment...
February 25, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28236663/catalytic-competence-structure-and-stability-of-the-cancer-associated-r139w-variant-of-the-human-nad-p-h-quinone-oxidoreductase-1-nqo1
#11
Wolf-Dieter Lienhart, Emilia Strandback, Venugopal Gudipati, Karin Koch, Alexandra Binter, Michael K Uhl, David M Rantasa, Benjamin Bourgeois, Tobias Madl, Klaus Zangger, Karl Gruber, Peter Macheroux
The human NAD(P)H:quinone oxidoreductase 1 (NQO1; EC 1.6.99.2) is an essential enzyme in the antioxidant defence system. Furthermore, NQO1 protects tumour suppressors like p53, p33(ING)(1b) and p73 from proteasomal degradation. The activity of NQO1 is also exploited in chemotherapy for the activation of quinone-based treatments. Various single nucleotide polymorphisms are known, such as NQO1*2 and NQO1*3 yielding protein variants of NQO1 with single amino acid replacements, i.e. P187S and R139W, respectively...
February 25, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28236662/monomer-to-dimer-transition-of-brucella-suis-type-iv-secretion-system-component-virb8-induces-conformational-changes
#12
Mahzad Sharifahmadian, Tarun Arya, Benoit Bessette, Lauriane Lecoq, Edward Ruediger, James G Omichinski, Christian Baron
Secretion systems are protein complexes essential for bacterial virulence and potential targets for anti-virulence drugs. In the intracellular pathogen Brucella suis, a type IV secretion system mediates the translocation of virulence factors into host cells and it is essential for pathogenicity. VirB8 is a core component of the secretion system and dimerization is important for functionality of the protein complex. We set out to study dimerization and possible conformational changes of VirB8 from Brucella suis (VirB8s) using nuclear magnetic resonance, X-ray crystallography and differential scanning fluorimetry...
February 25, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28236661/fam20c-is-under-the-control-of-sphingolipid-signalling-in-human-cell-lines
#13
Giorgio Cozza, Mauro Salvi, Vincent S Tagliabracci, Lorenzo A Pinna
Fam20C, also termed DMP-4 (dentin matrix protein 4) and G-CK (Golgi casein kinase) is an atypical protein kinase committed with the phosphorylation of casein and a plethora of other secreted proteins. Fam20C has been implicated in a number of human pathologies related to bio-mineralization, phosphate homeostasis and neoplasia. The mode of regulation of Fam20C is still a matter of conjecture. In vitro, Fam20C activity is stimulated several fold by sphingosine. To gain in vivo information about the physiological relevance of this observation, three cell lines expressing endogenous Fam20C, and one in which Fam20C has been knocked out with CRISPR/Cas9 technology have been examined for Fam20C activity under basal conditions and where sphingosine has been depleted by treatment with myriocin...
February 25, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28231404/express-or-repress-the-transcriptional-dilemma-of-damaged-chromatin
#14
Ilaria Capozzo, Fabio Iannelli, Sofia Francia, Fabrizio d'Adda di Fagagna
The fine modulation of transcriptional activity around DNA lesions is essential to carefully regulate the crosstalk between transcription, the DNA damage response, and DNA repair, particularly when the lesion occurs next to, or within, actively transcribed genes. Recently, several studies have been carried out to investigate how DNA lesions have an impact on local transcription, but the emerging model remains incomplete. Transcription of genes around damaged DNA is actively down-regulated by the DNA damage response through different mechanisms, which appear specific to the chromatin context, the type of DNA damage or its complexity...
February 23, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28222489/characterization-of-a-novel-signal-transducer-element-intrinsic-to-class-iiia-b-adenylate-cyclases-and-guanylate-cyclases
#15
Miriam Ziegler, Jens Bassler, Stephanie Beltz, Anita Schultz, Andrei N Lupas, Joachim E Schultz
Adenylate cyclases (ACs) are signalling proteins that produce the second messenger cAMP. Class III ACs comprises four groups (class IIIa-d); of these, class IIIa and IIIb ACs have been identified in bacteria and eukaryotes. Many class IIIa ACs are anchored to membranes via hexahelical domains. In eukaryotic ACs, membrane anchors are well conserved, suggesting that this region possesses important functional characteristics that are as yet unknown. To address this question, we replaced the hexahelical membrane anchor of the mycobacterial AC Rv1625c by the hexahelical quorum-sensing receptor from Legionella, LqsS...
February 21, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28222482/functional-reconstitution-of-the-mycobacterium-tuberculosis-long-chain-acyl-coa-carboxylase-from-multiple-acyl-coa-subunits
#16
Bernardo Bazet Lyonnet, Lautaro Diacovich, Gabriela Gago, Lucie Spina, Fabienne Bardou, Anne Lemassu, Annaïk Quémard, Hugo Gramajo
Mycobacterium tuberculosis produces a large number of structurally diverse lipids that have been implicated in the pathogenicity, persistence and antibiotic resistance of this organism. Most building blocks involved in the biosynthesis of all these lipids are generated by acyl-CoA carboxylases (ACCase) whose subunit composition and physiological roles have not yet been clearly established. A rather controversial data in the literature refers to the exact protein composition and substrate specificity of the enzyme complex that produces the long-chain α-carboxy-acyl-CoAs; one of the substrates involved in the last step of condensation mediated by the polyketide synthase Pks13 to synthesize mature mycolic acids...
February 21, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28207202/the-polar-warhead-of-a-trim24-bromodomain-inhibitor-rearranges-a-water-mediated-interaction-network
#17
Jiuyang Liu, Fudong Li, Hongyu Bao, Yiyang Jiang, Shuya Zhang, Rongsheng Ma, Jia Gao, Jihui Wu, Ke Ruan
Tripartite motif-containing protein 24 (TRIM24) is closely correlated with multiple cancers, and a recent study demonstrated that the bromodomain of TRIM24 is essential for the proliferation of lethal castration-resistant prostate cancer. Here, we identify three new inhibitors of the TRIM24 bromodomain using NMR fragment-based screening. The crystal structures of two new inhibitors in complex with the TRIM24 bromodomain reveal that the water-bridged interaction network is conserved in the same fashion as those for known benzoimidazolone inhibitors...
February 16, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28207191/cysteine-proteases-in-atherosclerosis
#18
REVIEW
Tommy Weiss Sadan, Israel Gotsman, Galia Blum
Atherosclerosis predisposes patients to cardiovascular diseases, such as myocardial infarction and stroke. Instigation of vascular injury is triggered by retention of lipids and inflammatory cells in the vascular endothelium. Whereas these vascular lesions develop in young adults and are mostly considered harmless, over time persistent inflammatory and remodeling processes will ultimately damage the arterial wall and cause a thrombotic event due to exposure of tissue factors into the lumen. Evidence from human tissues and pre-clinical animal models have clearly established the role of cathepsin cysteine proteases in the development and progression of vascular lesions...
February 16, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28207183/combining-the-auxin-inducible-degradation-system-with-crispr-cas9-based-genome-editing-for-the-conditional-depletion-of-endogenous-drosophila-melanogaster-proteins
#19
Melinda Bence, Ferenc Jankovics, Tamás Lukácsovich, Miklós Erdélyi
Inducible protein degradation techniques have considerable advantages over classical genetic approaches, which generate loss-of-function phenotypes at the gene or mRNA level. The plant-derived auxin-inducible degradation system (AID) is a promising technique which enables the degradation of target proteins tagged with the AID motif in non-plant cells. Here, we present a detailed characterization of this method employed during the adult oogenesis of Drosophila. Furthermore, with the help of CRISPR/Cas9-based genome editing, we improve the utility of the AID system in the conditional elimination of endogenously expressed proteins...
February 16, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28196299/activity-based-probes-for-the-ubiquitin-conjugation-deconjugation-machinery-new-chemistries-new-tools-and-new-insights
#20
REVIEW
David S Hewings, John A Flygare, Matthew Bogyo, Ingrid E Wertz
The reversible post-translational modification of proteins by ubiquitin and ubiquitin-like proteins regulates almost all cellular processes, by affecting protein degradation, localization, and complex formation. Deubiquitinases (DUBs) are proteases that remove ubiquitin modifications or cleave ubiquitin chains. Most DUBs are cysteine proteases, which makes them well suited for study by activity-based probes. These DUB probes report on deubiquitinase activity by reacting covalently with the active site in an enzyme-catalyzed manner...
February 14, 2017: FEBS Journal
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