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Biological Chemistry

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https://www.readbyqxmd.com/read/29140786/selection-of-an-anticalin%C3%A2-against-the-membrane-form-of-hsp70-via-bacterial-surface-display-and-its-theranostic-application-in-tumour-models
#1
Lars Friedrich, Petra Kornberger, Claudia T Mendler, Gabriele Multhoff, Markus Schwaiger, Arne Skerra
We describe the selection of Anticalins against a common tumour surface antigen, human Hsp70, using functional display on live E. coli cells as fusion with a truncated EspP autotransporter. While found intracellularly in normal cells, Hsp70 is frequently exposed in a membrane-bound state on the surface of tumour cells and, even more pronounced, in metastases or after radiochemotherapy. Employing a recombinant Hsp70 fragment comprising residues 383-548 as target, Anticalins were selected from a naive bacterial library...
November 27, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/29016349/structural-mechanisms-of-hect-type-ubiquitin-ligases
#2
REVIEW
Sonja Lorenz
Ubiquitin ligases (E3 enzymes) transfer ubiquitin from ubiquitin-conjugating (E2) enzymes to target proteins. By determining the selection of target proteins, modification sites on those target proteins, and the types of ubiquitin modifications that are formed, E3 enzymes are key specificity factors in ubiquitin signaling. Here, I summarize our knowledge of the structural mechanisms in the HECT E3 subfamily, many members of which play important roles in human disease. I discuss interactions of the conserved HECT domain with E2 enzymes, ubiquitin and target proteins, as well as macromolecular interactions with regulatory functions...
November 8, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/29040060/structure-and-function-of-the-human-parvulins-pin1-and-par14-17
#3
Anja Matena, Edisa Rehic, Dana Hönig, Bianca Kamba, Peter Bayer
Parvulins belong to the family of peptidyl-prolyl cis/trans isomerases (PPIases) assisting in protein folding and in regulating the function of a broad variety of proteins in all branches of life. The human representatives Pin1 and Par14/17 are directly involved in processes influencing cellular maintenance and cell fate decisions such as cell-cycle progression, metabolic pathways and ribosome biogenesis. This review on human parvulins summarizes the current knowledge of these enzymes and intends to oppose the well-studied Pin1 to its less well-examined homolog human Par14/17 with respect to structure, catalytic and cellular function...
October 26, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/29016350/a-novel-design-of-ha-coated-nanoparticles-co-encapsulating-plasmid-metase-and-5-fu-shows-enhanced-application-in-targeting-gastric-cancer-stem-cells
#4
Weifeng Yanga, Houting Zhanga, Lin Xin
Nanoparticles (NPs) is recognized as an attractive vehicles for cancer treatment due to their targeting drug release. Gastric cancer is an important death-related disease, and its therapy methods still need improvement. The NPs were prepared using a precipitation method, and were evaluated using transmission electron microscopy (TEM). MTT and Transwell assays were used to determine cell viability and apoptosis. In vivo experiments were performed to validate the effects of NPs on tumor growth. METase/5-Fu co-encaspulated NPs showed highest zeta size and lowest zeta potential than other NPs...
October 26, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/29016348/parp-1-and-parp-2-activity-in-cancer-induced-cachexia-potential-therapeutic-implications
#5
Esther Barreiro, Joaquim Gea
Skeletal muscle dysfunction and mass loss is a characteristic feature in patients with chronic diseases including cancer and acute conditions such as critical illness. Maintenance of an adequate muscle mass is crucial for the patients' prognosis irrespective of the underlying condition. Moreover, aging-related sarcopenia may further aggravate the muscle wasting process associated with chronic diseases and cancer. Poly(adenosine diphosphate-ribose) polymerase (PARP) activation has been demonstrated to contribute to the pathophysiology of muscle mass loss and dysfunction in animal models of cancer-induced cachexia...
October 26, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28976892/mechanisms-pathophysiological-roles-and-methods-for-analyzing-mitophagy-recent-insights
#6
Jessica A Williams, Wen-Xing Ding
In 2012, we briefly summarized the mechanisms, pathophysiological roles and methods for analyzing mitophagy. Since then, the mitophagy field has continued to grow rapidly, and many new molecular mechanisms regulating mitophagy and molecular tools for monitoring mitophagy have been discovered and developed. Therefore, the purpose of this review is to update information regarding these advances in mitophagy while focusing on basic molecular mechanisms of mitophagy in different organisms and its pathophysiological roles...
September 26, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28976890/how-to-get-rid-of-mitochondria-crosstalk-and-regulation-of-multiple-mitophagy-pathways
#7
Marcel Zimmermann, Andreas S Reichert
Mitochondria are indispensable cellular organelles providing ATP and numerous other essential metabolites to ensure cell survival. Reactive oxygen species (ROS), which are formed as side reactions during oxidative phosphorylation or by external agents, induce molecular damage in mitochondrial proteins, lipids/membranes, and DNA. To cope with this and other sorts of organellar stress, a multi-level quality control system exists to maintain cellular homeostasis. One critical level of mitochondrial quality control is the removal of damaged mitochondria by mitophagy...
September 26, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28976889/the-dinoponeratoxin-peptides-from-the-giant-ant-dinoponera-quadriceps-display-in-vitro-antitrypanosomal-activity
#8
Dânya Bandeira Lima, Clarissa Perdigão Mello, Izabel Cristina Justino Bandeira, Ramon Róseo Paula Pessoa Bezerra de Menezes, Tiago Lima Sampaio, Cláudio Borges Falcão, Jean-Étienne R L Morlighem, Gandhi Rádis-Baptista, Alice Maria Costa Martins
The crude venom of the giant ant Dinoponera quadriceps is a cocktail of polypeptides and organic compounds that showed antiparasitic effects against Trypanosoma cruzi, the causative agent of Chagas disease. In order to investigate the venom-derived components responsible for such antitrypanosomal activity, four dinoponeratoxins were identified, namely M-PONTX-Dq3a, -Dq3b, -Dq3c and -Dq4e, that are diverse in size, net charge, hydrophobicity and propensity to interact with eukaryote cell membranes. These peptides were tested against epimastigote, trypomastigote and amastigote forms of benznidazoleresistant Y strain of T...
September 26, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28885980/domain-topology-of-human-rasal
#9
Jorge Cuellar, José María Valpuesta, Alfred Wittinghofer, Begoña Sot
Rasal is a modular multi-domain protein of the GAP1 (GTPase-activating protein 1) family; its four known members, GAP1m, Rasal, GAP1IP4BP and Capri, have a Ras GTPase-activating domain (RasGAP). This domain supports the intrinsically slow GTPase activity of Ras by actively participating in the catalytic reaction. In the case of Rasal, GAP1IP4BP and Capri, their remaining domains are responsible for converting the RasGAP domains into dual Ras- and Rap-GAPs, via an incompletely understood mechanism. Although Rap proteins are small GTPase homologues of Ras, their catalytic residues are distinct, which reinforces the importance of determining the structure of full-length GAP1 family proteins...
September 26, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/29140789/mechanism-and-dynamics-of-inpp5e-transport-into-and-inside-the-ciliary-compartment
#10
Stefanie Kristine Kösling, Eyad Kalawy Fansa, Stefano Maffini, Alfred Wittinghofer
The inositol polyphosphate 5´-phosphatase E (INPP5E) localizes to cilia. We showed that the carrier protein phosphodiesterase 6 delta subunit (PDE6δ) mediates the sorting of farnesylated INPP5E into cilia due to high affinity binding and release by Arl3 GTP. However, the dynamics of INPP5E transport into and inside the ciliary compartment are not fully understood. Here we first investigate the movement of INPP5E using live cell fluorescence microscopy and fluorescence recovery after photobleaching (FRAP) analysis...
August 28, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/29140788/impact-of-protamine-i-on-colon-cancer-proliferation-invasion-migration-diagnosis-and-prognosis
#11
Zhi Chen, Chunyu Shi, Shuohui Gao, Ye Feng
The paper investigated the Protamine I (PRM1) expression and its effects on proliferation, invasion and migration of colon cancer cells as well as its function in clinical diagnosis and prognosis. Gene chips were used to screen differentially expressed genes. PRM1 expression was detected by Western blotting and qRT-PCR. HE staining and immunohistochemistry were utilized to compare the expression of PRM1 from multiple differentiation levels of colon cancer tissues. Cell viability, cell apoptosis and cell cycle were tested by MTT assay and flow cytometry...
August 28, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/29140787/tgf-%C3%AE-requires-the-activation-of-canonical-and-non-canonical-signalling-pathways-to-induce-skeletal-muscle-atrophy
#12
Johanna Ábrigo, Fabian Campos, Felipe Simon, Claudia Riedel, Daniel Cabrera, Cristian Vilos, Claudio Cabello-Verrugio
The transforming growth factor type beta (TGF-β) induces skeletal muscle atrophy characterized by a decrease in fiber's diameter and levels of myosin heavy chain (MHC), also as an increase of MuRF-1 expression. In addition, TGF-β induces muscle atrophy by a mechanism dependent on reactive oxygen species (ROS). TGF-β signals by activating both canonical Smad-dependent, and non-canonical signalling pathways such as ERK1/2, JNK1/2, and p38 MAPKs. However, the participation of canonical and non-canonical signalling pathways in the TGF-β atrophic effect on skeletal muscle is unknown...
August 28, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28858842/the-consequences-of-deglycosylation-of-recombinant-intra-melanosomal-domain-of-human-tyrosinase
#13
Monika B Dolinska, Yuri V Sergeev
Tyrosinase, a melanosomal glycoenzyme, catalyzes initial steps of the melanin biosynthesis. While glycosylation was previously studied in vivo, we present three recombinant mutant variants of human tyrosinase, which were obtained using multiple site-directed mutagenesis, expressed in insect larvae, purified, and characterized biochemically. The mutagenesis demonstrated the reduced protein expression and enzymatic activity due to possible loss of protein stability and protein degradation. However, the complete deglycosylation of asparagine residues in vitro, including the residue in position 371, interrupts tyrosinase function, which is consistent with a melanin loss in OCA1 patients...
August 28, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28850541/targeted-degradomics-in-protein-terminomics-and-protease-substrate-discovery
#14
Simonas Savickas, Ulrich Auf dem Keller
Targeted degradomics integrates positional information into mass spectrometry-based targeted proteomics workflows and thereby enables analysis of proteolytic cleavage events with unprecedented specificity and sensitivity. Rapid progress in establishment of protease-substrate relations provides extensive degradomics target lists that now can be tested with help of selected and parallel reaction monitoring (S/PRM) in complex biological systems, where proteases act in physiological environments. In this minireview, we describe the general principles of targeted degradomics, outline the generic experimental workflow of the methodology and highlight recent and future applications in protease research...
August 28, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28850540/maintaining-protein-composition-in-cilia
#15
Louise A Stephen, Yasmin Elmaghloob, Shehab Ismail
The primary cilium is a sensory organelle that is vital in regulating several signalling pathways. Unlike most organelles cilia are open to the rest of the cell, not enclosed by membranes. The distinct protein composition is crucial to the function of cilia and many signalling proteins and receptors are specifically concentrated within distinct compartments. To maintain this composition, a mechanism is required to deliver proteins to the cilium whilst another must counter the entropic tendency of proteins to distribute throughout the cell...
August 28, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28822221/brain-plasticity-cognitive-functions-and-neural-stem-cells-a-pivotal-role-for-the-brain-specific-neural-master-gene-srgap2-fam72
#16
Nguyen Thi Thanh Ho, Arne Kutzner, Klaus Heese
Due to an aging society with an increased dementia-induced threat to higher cognitive functions, it has become imperative to understand the molecular and cellular events controlling the memory and learning processes in the brain. Here, we suggest that the novel master gene pair |-SRGAP2-FAM72-| (SLIT-ROBO Rho GTPase activating protein 2 - family with sequence similarity to 72) reveals a new dogma for the regulation of neural stem cell (NSC) gene expression and is a distinctive player in the control of human brain plasticity...
August 28, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28822220/eremophilane-type-sesquiterpenes-from-fungi-and-their-medicinal-potential
#17
Kamila Tomoko Yuyama, Diana Fortkamp, Wolf-Rainer Abraham
Eremophilanes are sesquiterpenes with a rearranged carbon skeleton formed both by plants and fungi, however, almost no plant eremophilanes are found in fungi. These eremophilanes possess mainly phytotoxic, antimicrobial, anticancer and immunomodulatory properties and in this review fungal eremophilanes with bioactivities of potential medicinal applications are reviewed and discussed. A special focus is set on natural products bearing highly functionalized fatty acids at C-1 or C-3 position of the eremophilane backbone...
August 28, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28822218/locally-produced-xenin-and-the-neurotensinergic-system-in-pancreatic-islet-function-and-%C3%AE-cell-survival
#18
Dawood Khan, Srividya Vasu, R Charlotte Moffett, Victor A Gault, Peter R Flatt, Nigel Irwin
Modulation of neuropeptide receptors is important for pancreatic β-cell function. Here, islet distribution and effects of the neurotensin (NT) receptor modulators, xenin and NT, was examined. Xenin, but not NT, significantly improved glucose disposal and insulin secretion, in mice. However, both peptides stimulated insulin secretion from rodent β-cells at 5.6 mM glucose, with xenin having similar insulinotropic actions at 16.7 mM glucose. In contrast, NT inhibited glucose-induced insulin secretion. Similar observations were made in human 1...
August 28, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28822219/regulation-of-protein-function-by-s-nitrosation-and-s-glutathionylation-processes-and-targets-in-cardiovascular-pathophysiology
#19
REVIEW
Eugenia Belcastro, Caroline Gaucher, Alessandro Corti, Pierre Leroy, Isabelle Lartaud, Alfonso Pompella
Decades of chemical, biochemical and pathophysiological research have established the relevance of post-translational protein modifications induced by processes related to oxidative stress, with critical reflections on cellular signal transduction pathways. A great deal of the so-called 'redox regulation' of cell function is in fact mediated through reactions promoted by reactive oxygen and nitrogen species on more or less specific aminoacid residues in proteins, at various levels within the cell machinery...
November 27, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28802097/heat-shock-protein-47-effects-on-hepatic-stellate-cell-associated-receptors-in-hepatic-fibrosis-of-schistosoma-japonicum-infected-mice
#20
Yumin Zhao, Zhisheng Dang, Shuo Xu, Shigui Chong
The study aimed to explore the regulation of heat shock protein 47 (HSP47) on expressions of receptors associated with hepatic stellate cell (HSC) in liver fibrosis mouse models induced by Schistosoma japonicum (S. japonicum). Mouse fibroblasts (NIH/3T3) were transfected with HSP47 shRNA plasmid by lipofectamine transfection, and experimental fibrosis in HSCs was studied in S. japonicum mouse models treated with HSP47 shRNA in vivo. HSP47 expression was assessed using Western blot and real-time PCR. Flow cytometry was adopted to determine the expression of cell membrane receptors...
November 27, 2017: Biological Chemistry
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