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https://www.readbyqxmd.com/read/28653811/biochemical-characterization-of-medaka-oryzias-latipes-orthologue-for-mammalian-factor-xiii-and-establishment-of-gene-edited-mutant
#1
Rima Horimizu, Ryota Ogawa, Yuko Watanabe, Hideki Tatsukawa, Masato Kinoshita, Hisashi Hashimoto, Kiyotaka Hitomi
At the final process of blood coagulation, fibrin molecules are stabilized via a catalytic reaction by Factor XIIIA (FXIIIA), one of the family members of transglutaminase (TGase) that catalyzes protein cross-linking reactions. In this study, we characterized the orthologue of this enzyme in medaka (Oryzias latipes), an established model fish in which a coagulation system is also preserved. The recombinant protein of this orthologue enzyme was produced in baculovirus-infected insect cells and used for biochemical property analysis including activation by thrombin-proteolysis and calcium-dependence of the TGase enzymatic activity...
June 27, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28648785/lc-ms-bioanalysis-of-trastuzumab-and-released-emtansine-using-nano-surface-and-molecular-orientation-limited-nsmol-proteolysis-and-liquid-liquid-partition-in-plasma-of-trastuzumab-emtansine-treated-breast-cancer-patients
#2
Noriko Iwamoto, Akihiko Shimomura, Kenji Tamura, Akinobu Hamada, Takashi Shimada
Antibody-drug conjugates (ADCs) consist of monoclonal antibody and cytotoxic drugs covalently attached via stable crosslinkers, and are prospective antibody drugs for cancer therapy. To cover the overall pharmacokinetic understanding of ADCs, both the antibody and the released drugs are necessary for practical clinical observation. The nano-surface and molecular-orientation limited (nSMOL) proteolysis is a universal approach for antibody bioanalysis that enable Fab-selective proteolysis, which maintains antibody sequence specificity while decreasing excess analyte peptides...
June 19, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28648610/glycan-activation-of-a-sheddase-electrostatic-recognition-between-heparin-and-prommp-7
#3
Yan G Fulcher, Stephen H Prior, Sayaka Masuko, Lingyun Li, Dennis Pu, Fuming Zhang, Robert J Linhardt, Steven R Van Doren
Heparan sulfate proteoglycans activate the matrix metalloproteinase-7 zymogen (proMMP-7) and recruit it in order to shed proteins from cell surfaces. This occurs in uterine and mammary epithelia, bacterial killing, lung healing, and tumor cell signaling. Basic tracks on proMMP-7 recognize polyanionic heparin, according to nuclear magnetic resonance and mutations disruptive of maturation. Contacts and proximity measurements guided docking of a heparin octasaccharide to proMMP-7. The reducing end fits into a basic pocket in the pro-domain while the chain continues toward the catalytic domain...
June 12, 2017: Structure
https://www.readbyqxmd.com/read/28648379/targeted-protein-degradation-from-chemical-biology-to-drug-discovery
#4
REVIEW
Philipp M Cromm, Craig M Crews
Traditional pharmaceutical drug discovery is almost exclusively focused on directly controlling protein activity to cure diseases. Modulators of protein activity, especially inhibitors, are developed and applied at high concentration to achieve maximal effects. Thereby, reduced bioavailability and off-target effects can hamper compound efficacy. Nucleic acid-based strategies that control protein function by affecting expression have emerged as an alternative. However, metabolic stability and broad bioavailability represent development hurdles that remain to be overcome for these approaches...
June 10, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28646136/recurrent-background-mutations-in-whi2-impair-proteostasis-and-degradation-of-misfolded-cytosolic-proteins-in-saccharomyces-cerevisiae
#5
Sophie A Comyn, Stéphane Flibotte, Thibault Mayor
Proteostasis promotes viability at both the cellular and organism levels by maintaining a functional proteome. This requires an intricate protein quality control (PQC) network that mediates protein folding by molecular chaperones and removes terminally misfolded proteins via the ubiquitin proteasome system and autophagy. How changes within the PQC network can perturb proteostasis and shift the balance between protein folding and proteolysis remain poorly understood. However, given that proteostasis is altered in a number of conditions such as cancer and ageing, it is critical that we identify the factors that mediate PQC and understand the interplay between members of the proteostatic network...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646121/at1-receptor-blockade-attenuates-outward-aortic-remodeling-associated-with-diet-induced-obesity-in-mice
#6
Friedrich Krueger, Kai Kappert, Anna Foryst-Ludwig, Frederike Kramer, Markus Clemenz, Aleksandra Grzesiak, Manuela Sommerfeld, Jan Paul Bernhard Frese, Andreas Greiner, Ulrich Kintscher, Thomas Unger, Elena Kaschina
The renin-angiotensin-system and obesity have been implicated in vascular outward remodeling, including aneurysms, but the precise mechanisms are yet not understood. We investigated the effect of the angiotensin AT1-receptor antagonist telmisartan on aortic outward remodeling in a diet-induced obesity-model in mice. C57/Black6J mice were fed with either a low-fat diet (LFD), or a high-fat diet (HFD) for 14 weeks. One group of HFD-mice was additionally exposed to telmisartan (3mg/kg/d) for the last 4 weeks. HFD led to aortic outward remodeling, characterized by increased proteolysis, along with structural changes, such as fragmentation of elastic fibres, and decreased elastin content...
June 23, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28642633/proteases-revisited-roles-and-therapeutic-implications-in-fibrosis
#7
REVIEW
Jakub Kryczka, Joanna Boncela
Proteases target many substrates, triggering changes in distinct biological processes correlated with cell migration, EMT/EndMT and fibrosis. Extracellular protease activity, demonstrated by secreted and membrane-bound protease forms, leads to ECM degradation, activation of other proteases (i.e., proteolysis of nonactive zymogens), decomposition of cell-cell junctions, release of sequestered growth factors (TGF-β and VEGF), activation of signal proteins and receptors, degradation of inflammatory inhibitors or inflammation-related proteins, and changes in cell mechanosensing and motility...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28640887/epidermal-growth-factor-promotes-cyclin-g2-degradation-via-calpain-mediated-proteolysis-in-gynaecological-cancer-cells
#8
Stefanie Bernaudo, Shahin Khazai, Eilyad Honarparvar, Alina Kopteva, Chun Peng
Cyclin G2 (CCNG2) is an atypical cyclin that functions to inhibit cell cycle progression and is often dysregulated in human cancers. We have previously shown that cyclin G2 is highly unstable and can be degraded through the ubiquitin/proteasome pathway. Furthermore, cyclin G2 contains a PEST domain, which has been suggested to act as a signal for degradation by multiple proteases. In this study, we determined if calpains, a family of calcium-dependent proteases, are also involved in cyclin G2 degradation. The addition of calpain inhibitors or silencing of calpain expression by siRNAs strongly enhanced cyclin G2 levels...
2017: PloS One
https://www.readbyqxmd.com/read/28638003/molecular-and-cellular-events-during-blastocyst-implantation-in-the-receptive-uterus-clues-from-mouse-models
#9
Hiromichi Matsumoto
The success of implantation is an interactive process between the blastocyst and the uterus. Synchronized development of embryos with uterine differentiation to a receptive state is necessary to complete pregnancy. The period of uterine receptivity for implantation is limited and referred to as the "implantation window", which is regulated by ovarian steroid hormones. Implantation process is complicated due to the many signaling molecules in the hierarchical mechanisms with the embryo-uterine dialogue. The mouse is widely used in animal research, and is uniquely suited for reproductive studies, i...
June 22, 2017: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/28636874/next-generation-matrix-metalloproteinase-inhibitors-novel-strategies-bring-new-prospects
#10
REVIEW
Maxim Levin, Yael Udi, Inna Solomonov, Irit Sagi
Enzymatic proteolysis of cell surface proteins and extracellular matrix (ECM) is critical for tissue homeostasis and cell signaling. These proteolytic activities are mediated predominantly by a family of proteases termed matrix metalloproteinases (MMPs). The growing evidence in recent years that ECM and non-ECM bioactive molecules (e.g., growth factors, cytokines, chemokines, on top of matrikines and matricryptins) have versatile functions redefines our view on the roles matrix remodeling enzymes play in many physiological and pathological processes, and underscores the notion that ECM proteolytic reaction mechanisms represent master switches in the regulation of critical biological processes and govern cell behavior...
June 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28636052/chemically-induced-degradation-of-cdk9-by-a-proteolysis-targeting-chimera-protac
#11
Caroline M Robb, Jacob I Contreras, Smit Kour, Margaret A Taylor, Mohammad Abid, Yogesh A Sonawane, Muhammad Zahid, Daryl J Murry, Amarnath Natarajan, Sandeep Rana
Cyclin-dependent kinase 9 (CDK9), a member of the cyclin-dependent protein kinase (CDK) family, is involved in transcriptional elongation of several target genes. CDK9 is ubiquitously expressed and has been shown to contribute to a variety of malignancies such as pancreatic, prostate and breast cancers. Here we report the development of a heterobifunctional small molecule proteolysis targeting chimera (PROTAC) capable of cereblon (CRBN) mediated proteasomal degradation of CDK9. In HCT116 cells, it selectively degrades CDK9 while sparing other CDK family members...
June 21, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28634175/interrelations-between-3-hydroxypropionate-and-propionate-metabolism-in-rat-liver-relevance-to-disorders-of-propionyl-coa-metabolism
#12
Kirkland A Wilson, Yong Han, Miaoqi Zhang, Jeremy Hess, Kimberly A Chapman, Gary W Cline, Gregory P Tochtrop, Henri Brunengraber, Guo-Fang Zhang
Propionate, 3-hydroxypropionate (3HP), methylcitrate, related compounds and ammonium accumulate in body fluids of patients with disorders of propionyl-CoA metabolism, such as propionic acidemia. Although liver transplantation alleviates hyperammonemia, high concentrations of propionate, 3HP and methylcitrate persist in body fluids. We hypothesized that conserved metabolic perturbations occurring in transplanted patients result from the simultaneous presence of propionate and 3HP in body fluids. We investigated the interrelations of propionate and 3HP metabolism in perfused livers from normal rats using metabolomic and stable isotopic technologies...
June 20, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28633832/effects-of-ultrasound-on-the-beef-structure-and-water-distribution-during-curing-through-protein-degradation-and-modification
#13
Da-Cheng Kang, Xue-Qin Gao, Qing-Feng Ge, Guang-Hong Zhou, Wan-Gang Zhang
The objective of this study was to explore the mechanisms of power ultrasound (PUS, 150 and 300W) and treatment time (30 and 120min) on the water-holding capacity (WHC) and tenderness of beef during curing. Beef muscle at 48h post mortem was subjected to PUS treatment at a frequency of 20kHz. Analysis of compression loss and shear force showed that PUS-assisted curing significantly increased the WHC and the tenderness of beef compared to static brining (p<0.05). According to the analysis of LF-NMR, PUS treatment could increase the P21 values which indicated an improvement in water-binding ability of beef muscle...
September 2017: Ultrasonics Sonochemistry
https://www.readbyqxmd.com/read/28632996/taking-control-hijacking-of-rab-gtpases-by-intracellular-bacterial-pathogens
#14
Stefania Spanò, Jorge E Galán
Intracellular bacterial pathogens survive and replicate within specialized eukaryotic cell organelles. To establish their intracellular niches these pathogens have adopted sophisticated strategies to control intracellular membrane trafficking. Since Rab-family GTPases are critical regulators of endocytic and secretory membrane trafficking events, many intracellular pathogens have evolved specific mechanisms to modulate or hijack Rab GTPases dynamics and trafficking functions. One such strategy is the delivery of bacterial effectors through specialized machines to specifically target Rab GTPases...
June 20, 2017: Small GTPases
https://www.readbyqxmd.com/read/28630798/the-role-of-cullin4b-in-human-cancers
#15
REVIEW
Ying Li, Xin Wang
Cullin 4B (CUL4B) is a scaffold of the Cullin4B-Ring E3 ligase complex (CRL4B) that plays an important role in proteolysis and is implicated in tumorigenesis. Aberrant expression of CUL4B has been reported in various types of human diseases. Recently, studies have shown that CUL4B was overexpressed in a multitude of solid neoplasms and affect the expression of several tumor suppressor genes. In this review, we aim to summarize the biological function of CUL4B in order to better understand its pathogenesis in human cancers...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28628628/transcriptional-mechanisms-associated-with-seed-dormancy-and-dormancy-loss-in-the-gibberellin-insensitive-sly1-2-mutant-of-arabidopsis-thaliana
#16
Sven K Nelson, Camille M Steber
While widespread transcriptome changes were previously observed with seed dormancy loss, this study specifically characterized transcriptional changes associated with the increased seed dormancy and dormancy loss of the gibberellin (GA) hormone-insensitive sleepy1-2 (sly1-2) mutant. The SLY1 gene encodes the F-box subunit of an SCF E3 ubiquitin ligase needed for GA-triggered proteolysis of DELLA repressors of seed germination. DELLA overaccumulation in sly1-2 seeds leads to increased dormancy that can be rescued without DELLA protein destruction either by overexpression of the GA receptor, GA-INSENSITIVE DWARF1b (GID1b-OE) (74% germination) or by extended dry after-ripening (11 months, 51% germination)...
2017: PloS One
https://www.readbyqxmd.com/read/28628099/toxoplasma-depends-on-lysosomal-consumption-of-autophagosomes-for-persistent-infection
#17
Manlio Di Cristina, Zhicheng Dou, Matteo Lunghi, Geetha Kannan, My-Hang Huynh, Olivia L McGovern, Tracey L Schultz, Aric J Schultz, Alyssa J Miller, Beth M Hayes, Wouter van der Linden, Carla Emiliani, Matthew Bogyo, Sébastien Besteiro, Isabelle Coppens, Vern B Carruthers
Globally, nearly 2 billion people are infected with the intracellular protozoan Toxoplasma gondii(1). This persistent infection can cause severe disease in immunocompromised people and is epidemiologically linked to major mental illnesses(2) and cognitive impairment(3). There are currently no options for curing this infection. The lack of effective therapeutics is due partly to a poor understanding of the essential pathways that maintain long-term infection. Although it is known that Toxoplasma replicates slowly within intracellular cysts demarcated with a cyst wall, precisely how it sustains itself and remodels organelles in this niche is unknown...
June 19, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28626931/insecticide-resistance-and-intracellular-proteases
#18
REVIEW
Richard M Wilkins
Pesticide resistance is an example of evolution in action with mechanisms of resistance arising from mutations or increased expression of intrinsic genes. Intracellular proteases have a key role in maintaining healthy cells and in responding to stressors such as pesticides. Insecticide resistant insects have constitutively elevated intracellular protease activity when compared to corresponding susceptible strains. This increase was shown for some cases originally through biochemical enzyme studies and subsequently putatively by transcriptomics and proteomics methods...
June 19, 2017: Pest Management Science
https://www.readbyqxmd.com/read/28626118/mitochondrial-proteolysis-and-its-roles-in-stress-responses
#19
Shiori Sekine
No abstract text is available yet for this article.
2017: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
https://www.readbyqxmd.com/read/28625348/metabolic-regulation-of-the-pmca-role-in-cell-death-and-survival
#20
REVIEW
Jason I E Bruce
The plasma membrane Ca(2+)-ATPase (PMCA) is a ubiquitously expressed, ATP-driven Ca(2+) pump that is critical for maintaining low resting cytosolic Ca(2+) ([Ca(2+)]i) in all eukaryotic cells. Since cytotoxic Ca(2+) overload has such a central role in cell death, the PMCA represents an essential "linchpin" for the delicate balance between cell survival and cell death. In general, impaired PMCA activity and reduced PMCA expression leads to cytotoxic Ca(2+) overload and Ca(2+) dependent cell death, both apoptosis and necrosis, whereas maintenance of PMCA activity or PMCA overexpression is generally accepted as being cytoprotective...
June 8, 2017: Cell Calcium
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