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https://www.readbyqxmd.com/read/29166606/sumoylation-promotes-nuclear-import-and-stabilization-of-polo-like-kinase-1-to-support-its-mitotic-function
#1
Donghua Wen, Jianguo Wu, Lei Wang, Zheng Fu
As a pivotal mitotic regulator, polo-like kinase 1 (PLK1) is under highly coordinated and multi-layered regulation. However, the pathways that control PLK1's activity and function have just begun to be elucidated. PLK1 has recently been shown to be functionally modulated by post-translational modifications (PTMs), including phosphorylation and ubiquitination. Herein, we report that SUMOylation plays an essential role in regulating PLK1's mitotic function. We found that Ubc9 was recruited to PLK1 upon initial phosphorylation and activation by CDK1/cyclin B...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166597/mammalian-hp1-isoforms-have-specific-roles-in-heterochromatin-structure-and-organization
#2
Laia Bosch-Presegué, Helena Raurell-Vila, Joshua K Thackray, Jessica González, Carmen Casal, Noriko Kane-Goldsmith, Miguel Vizoso, Jeremy P Brown, Antonio Gómez, Juan Ausió, Timo Zimmermann, Manel Esteller, Gunnar Schotta, Prim B Singh, Lourdes Serrano, Alejandro Vaquero
HP1 is a structural component of heterochromatin. Mammalian HP1 isoforms HP1α, HP1β, and HP1γ play different roles in genome stability, but their precise role in heterochromatin structure is unclear. Analysis of Hp1α(-/-), Hp1β(-/-), and Hp1γ(-/-) MEFs show that HP1 proteins have both redundant and unique functions within pericentric heterochromatin (PCH) and also act globally throughout the genome. HP1α confines H4K20me3 and H3K27me3 to regions within PCH, while its absence results in a global hyper-compaction of chromatin associated with a specific pattern of mitotic defects...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166058/structural-entanglements-in-protein-complexes
#3
Yani Zhao, Mateusz Chwastyk, Marek Cieplak
We consider multi-chain protein native structures and propose a criterion that determines whether two chains in the system are entangled or not. The criterion is based on the behavior observed by pulling at both termini of each chain simultaneously in the two chains. We have identified about 900 entangled systems in the Protein Data Bank and provided a more detailed analysis for several of them. We argue that entanglement enhances the thermodynamic stability of the system but it may have other functions: burying the hydrophobic residues at the interface and increasing the DNA or RNA binding area...
June 14, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/29166011/a-cooperative-folding-unit-as-the-structural-link-for-energetic-coupling-within-a-protein
#4
Nathan W Gardner, Sarah M McGinness, Jainik Panchal, Elizabeth M Topp, Chiwook Park
Previously, we demonstrated that ligand binding to Escherichia coli cofactor-dependent phosphoglycerate mutase (dPGM), a homodimeric protein, is energetically coupled with dimerization. The equilibrium unfolding of dPGM occurs with a stable, monomeric intermediate. Binding of several non-substrate metabolites stabilizes the dimeric native form over the monomeric intermediate, reducing the population of the intermediate. Both the active site and the dimer interface appear to be unfolded in the intermediate. We hypothesized that a loop containing residues 118-152 was responsible for the energetic coupling between the dimer interface and the distal active site and was unfolded in the intermediate...
November 22, 2017: Biochemistry
https://www.readbyqxmd.com/read/29166010/conformational-dynamics-of-asparagine-at-coiled-coil-interfaces
#5
Franziska Thomas, Ai Niitsu, Alain Oregioni, Gail J Bartlett, Derek N Woolfson
Coiled coils (CCs) are among the best-understood protein folds. Nonetheless, there are gaps in our knowledge of CCs. Notably, CCs are likely to be structurally more dynamic than often considered. Here, we explore this in an abundant class of CCs, parallel dimers, focusing on polar asparagine (Asn) residues in the hydrophobic interface. It is well documented that such inclusions discriminate between different CC oligomers, which has been rationalized in terms of whether the Asn can make side-chain hydrogen bonds or not...
November 22, 2017: Biochemistry
https://www.readbyqxmd.com/read/29165690/the-regulatory-g4-motif-of-the-kirsten-ras-kras-gene-is-sensitive-to-guanine-oxidation-implications-on-transcription
#6
Susanna Cogoi, Annalisa Ferino, Giulia Miglietta, Erik B Pedersen, Luigi E Xodo
KRAS is one of the most mutated genes in human cancer. It is controlled by a G4 motif located upstream of the transcription start site. In this paper, we demonstrate that 8-oxoguanine (8-oxoG), being more abundant in G4 than in non-G4 regions, is a new player in the regulation of this oncogene. We designed oligonucleotides mimicking the KRAS G4-motif and found that 8-oxoG impacts folding and stability of the G-quadruplex. Dimethylsulphate-footprinting showed that the G-run carrying 8-oxoG is excluded from the G-tetrads and replaced by a redundant G-run in the KRAS G4-motif...
November 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29165439/proteomic-signatures-differentiating-bacillus-anthracis-sterne-sporulation-on-soil-relative-to-laboratory-media
#7
D S Wunschel, J R Hutchison, B L Deatherage Kaiser, E D Merkley, B M Hess, A Lin, M G Warner
The process of sporulation is vital for the stability and infectious cycle of Bacillus anthracis. The spore is the infectious form of the organism and therefore relevant to biodefense. While the morphological and molecular events occurring during sporulation have been well studied, the influence of growth medium and temperature on the proteins expressed in sporulated cultures is not well understood. Understanding the features of B. anthracis sporulation specific to natural vs. laboratory production will address an important question in microbial forensics...
November 22, 2017: Analyst
https://www.readbyqxmd.com/read/29165072/mpeg-pla-micelle-for-delivery-of-effective-parts-of-andrographis-paniculata
#8
Hailu Yao, Shiyong Song, Xiaolu Miao, Xiao Liu, Zhen Wang, Xiaoting Shao, Yu Zhang, Guang Han
Many studies have shown that Andrographis paniculata (Burm. f.) Nees has a good anti-tumor effect, but poor solubility in water and poor bioavailability hinder the modernization of it. To formulate the effective parts (mainly diterpene lactones) of Andrographis paniculata (AEP) into targeting drug delivery system, a series of poly(ethylene glycol)-poly(D.L-lactic acid)(mPEG-PLA) with different ratio of hydrophilic and hydrophobic segment were synthetized to encapsulate AEP. AEP micelles were prepared by a simple solvent-evaporation method...
November 19, 2017: Current Drug Delivery
https://www.readbyqxmd.com/read/29164633/capillarisin-blocks-prostate-specific-antigen-expression-on-activation-of-androgen-receptor-in-prostate-carcinoma-cells
#9
Ke-Hung Tsui, Ying-Ling Chang, Tsui-Hsia Feng, Chen-Pang Hou, Yu-Hsiang Lin, Pei-Shan Yang, Bing-Wei Lee, Horng-Heng Juang
BACKGROUND: Capillarisin (Cap), an active ingredient of Artemisia capillaris extracts, has known for its anti-inflammatory, antioxidant, and anticancer properties. Functions of Cap in prostate cancer are not clear. We investigate effects of Cap on downregulation of prostate specific antigen (PSA) via modulation of androgen receptor (AR) in prostate carcinoma cells. METHODS: Cell proliferation was measured by water-soluble tetrazolium-1 (WST-1) cell proliferation assays...
November 22, 2017: Prostate
https://www.readbyqxmd.com/read/29164147/dissection-of-factors-affecting-the-variability-of-the-peptide-bond-geometry-and-planarity
#10
Nicole Balasco, Luciana Esposito, Amarinder Singh Thind, Mario Rosario Guarracino, Luigi Vitagliano
Proteins frequently assume complex three-dimensional structures characterized by marginal thermodynamic stabilities. In this scenario, deciphering the folding code of these molecular giants with clay feet is a cumbersome task. Studies performed in last years have shown that the interplay between backbone geometry and local conformation has an important impact on protein structures. Although the variability of several geometrical parameters of protein backbone has been established, the role of the structural context in determining these effects has been hitherto limited to the valence bond angle τ (NC (α) C)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29163887/a-novel-peptide-stapling-strategy-enables-the-retention-of-ring-closing-amino-acid-side-chains-for-the-wnt-%C3%AE-catenin-signalling-pathway
#11
Ye Wu, Ye-Hua Li, Xiang Li, Yan Zou, Hong-Li Liao, Lei Liu, Ye-Guang Chen, Donald Bierer, Hong-Gang Hu
The all-hydrocarbon peptide stapling strategy has recently been extensively explored in drug discovery. There remains the potential for improvement regarding the retention of the amino acid side chains at the stapled positions. Herein, we describe a new series of amino acids that not only contain the native side chains, but also carry the alkenyl arms that are needed for the ring-closing stapling chemistry. We incorporate the new amino acids into a β-catenin-binding domain of Axin (469-482) and develop a new category of stapled peptides with the retention of the native side chains...
November 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29163781/synj2bp-promotes-the-degradation-of-pten-through-the-lysosome-pathway-and-enhances-breast-tumor-metastasis-via-pi3k-akt-snai1-signaling
#12
Miao Wang, Huijian Wu, Shujing Li, Zhaowei Xu, Xiahui Li, Yangyang Yang, Bowen Li, Yanan Li, Jing Guo, Huan Chen
SYNJ2BP plays an important role in breast cancer metastasis. However, the molecular mechanism associated with the function of SYNJ2BP in metastasis remains unclear. In this study, we investigated the role of SYNJ2BP in tumor metastasis and established the associated underlying mechanism. Over-expression of SYNJ2BP promoted both cell migration and invasion. In contrast, silencing SYNJ2BP caused the suppression of cell migration and invasion. SYNJ2BP increased the levels of phosphorylation for AKT and GSK3β, which could be inhibited by the PI3K inhibitor, LY294002, and the GSK3β inhibitor, LiCl, and regulated the accumulation of SNAI1 in the nucleus and the expression of the SNAI1 target gene, E-cadherin (EMT marker)...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163769/yap1-is-essential-for-tumor-growth-and-is-a-potential-therapeutic-target-for-egfr-dependent-lung-adenocarcinomas
#13
Ting-Fang Lee, Yu-Chi Tseng, Wei-Chin Chang, Yi-Chen Chen, Yu-Rung Kao, Teh-Ying Chou, Chao-Chi Ho, Cheng-Wen Wu
Epidermal growth factor receptor (EGFR) mutations are found in lung adenocarcinomas leading to tumor cells proliferation and survival. EGFR tyrosine kinase inhibitors (TKIs) that block EGFR activity are effective therapeutics for EGFR-mutant lung adenocarcinoma patients, but TKI-resistance inevitably occurs. The YES-associated protein (YAP1) transcription coactivator has been implicated as an oncogene and is amplified in human cancers and provides tumor cells strong proliferation and survival cues. This study investigated the roles of YAP1 in lung adenocarcinoma by exploring its regulation and functions mediated by EGFR signaling...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163405/overexpression-of-the-prunus-sogdiana-nbs-lrr-subgroup-gene-psorpm2-promotes-resistance-to-the-root-knot-nematode-meloidogyne-incognita-in-tobacco
#14
Xiang Zhu, Kun Xiao, Haiyang Cui, Jianfang Hu
Root-knot nematodes (RKNs), particularly Meloidogyne incognita, are the most devastating soil-borne pathogens that significantly affect the production of Prunus spp. fruit. RKN infection is difficult to control and consequently causes massive yield losses each year. However, several germplasms of wild Prunus spp. have been shown to display resistance to M. incognita. Consequently, both the isolation of novel plant resistance (R) genes and the characterization of their resistance mechanisms are important strategies for future disease control...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29163061/cyclodextrins-and-iatrogenic-hearing-loss-new-drugs-with-significant-risk
#15
REVIEW
Mark A Crumling, Kelly A King, R Keith Duncan
Cyclodextrins are a family of cyclic oligosaccharides with widespread usage in medicine, industry and basic sciences owing to their ability to solubilize and stabilize guest compounds. In medicine, cyclodextrins primarily act as a complexing vehicle and consequently serve as powerful drug delivery agents. Recently, uncomplexed cyclodextrins have emerged as potent therapeutic compounds in their own right, based on their ability to sequester and mobilize cellular lipids. In particular, 2-hydroxypropyl-β-cyclodextrin (HPβCD) has garnered attention because of its cholesterol chelating properties, which appear to treat a rare neurodegenerative disorder and to promote atherosclerosis regression related to stroke and heart disease...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29163012/iron-oxide-nanoparticle-delivery-of-peptides-to-the-brain-reversal-of-anxiety-during-drug-withdrawal
#16
Nathan Vinzant, Jamie L Scholl, Chia-Ming Wu, Trevor Kindle, Ranjit Koodali, Gina L Forster
Targeting neuropeptide systems is important for future advancements in treatment of neurological and psychiatric illnesses. However, many of the peptides and their analogs do not cross the blood-brain barrier (BBB) efficiently. Nanoparticles such as iron oxide can cross the BBB, and here we describe a novel method for the conjugation of a peptide antisauvagine-30 (ASV-30) to iron oxide nanoparticles. Previous research has shown that direct infusion of ASV-30 into the brain reduces anxiety-like behavior in animal models via actions on corticotropin releasing factor type 2 (CRF2) receptors...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29162966/a-qsar-model-of-olanzapine-derivatives-as-potential-inhibitors-for-5-ht2a-receptor
#17
Pooja Mitra, Aishwarya Rastogi, Mayank Rajpoot, Ajay Kumar, Vivek Srivastava
Schizophrenia is a complex, chronic mental disorder, affecting about 21 million people worldwide. It is characterized by symptoms, including distortions in thinking, perception, emotions, disorganized speech, sense of self and behavior. Recently, a numbers of marketed drugs for Schizophrenia are available against dopamine D2 and serotonin 5-HT2A receptors. Here, we docked Olanzapine derivatives (collected from literature) with 5-HT2A Receptor using the program AutoDock 4.2. The docked protein inhibitor complex structure was optimized using molecular dynamics simulation for 5ps with the CHARMM-22 force field using NAMD (NAnoscale Molecular Dynamics program) incorporated in visual molecular dynamics (VMD 1...
2017: Bioinformation
https://www.readbyqxmd.com/read/29162813/chemogenomic-analysis-reveals-key-role-for-lysine-acetylation-in-regulating-arc-stability
#18
Jasmin Lalonde, Surya A Reis, Sudhir Sivakumaran, Carl S Holland, Hendrik Wesseling, John F Sauld, Begum Alural, Wen-Ning Zhao, Judith A Steen, Stephen J Haggarty
The role of Arc in synaptic plasticity and memory consolidation has been investigated for many years with recent evidence that defects in the expression or activity of this immediate-early gene may also contribute to the pathophysiology of brain disorders including schizophrenia and fragile X syndrome. These results bring forward the concept that reversing Arc abnormalities could provide an avenue to improve cognitive or neurological impairments in different disease contexts, but how to achieve this therapeutic objective has remained elusive...
November 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29162742/microtubules-tune-mechanotransduction-through-nox2-and-trpv4-to-decrease-sclerostin-abundance-in-osteocytes
#19
James S Lyons, Humberto C Joca, Robert A Law, Katrina M Williams, Jaclyn P Kerr, Guoli Shi, Ramzi J Khairallah, Stuart S Martin, Konstantinos Konstantopoulos, Christopher W Ward, Joseph P Stains
The adaptation of the skeleton to its mechanical environment is orchestrated by mechanosensitive osteocytes, largely by regulating the abundance of sclerostin, a secreted inhibitor of bone formation. We defined a microtubule-dependent mechanotransduction pathway that linked fluid shear stress to reactive oxygen species (ROS) and calcium (Ca(2+)) signals that led to a reduction in sclerostin abundance in cultured osteocytes. We demonstrated that microtubules stabilized by detyrosination, a reversible posttranslational modification of polymerized α-tubulin, determined the stiffness of the cytoskeleton, which set the mechanoresponsive range of cultured osteocytes to fluid shear stress...
November 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/29162700/double-strand-dna-breaks-are-mainly-repaired-by-the-homologous-recombination-pathway-in-early-developing-swine-embryos
#20
Rodrigo C Bohrer, Naomi Dicks, Karina Gutierrez, Raj Duggavathi, Vilceu Bordignon
DNA double-strand breaks (DSBs) are less frequent than single-strand breaks but have more harmful consequences on cell survival and physiology. Homologous recombination (HR) and nonhomologous end-joining (NHEJ) are the two main pathways that are responsible for DSB repair in eukaryotic cells, but their importance for the preservation of genome stability in totipotent blastomeres of early developing embryos has not been determined. In this study, we observed that the chemical inhibition of HR or both pathways, but not NHEJ alone, increased the number of DSBs, reduced embryo development to the blastocyst stage, and resulted in embryos with higher proportions of apoptotic cells...
November 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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