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Protein turnover

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https://www.readbyqxmd.com/read/28547871/sequence-based-analysis-of-protein-degradation-rates-a-computational-study-of-protein-degradation
#1
Miguel Correa Marrero, Aalt D J van Dijk, Dick de Ridder
Protein turnover is a key aspect of cellular homeostasis and proteome dynamics. However, there is little consensus on which properties of a protein determine its lifetime in the cell. In this work, we exploit two reliable datasets of experimental protein degradation rates to learn models and uncover determinants of protein degradation, with particular focus on properties that can be derived from the sequence. Our work shows that simple sequence features suffice to obtain predictive models of which the output correlates reasonably well with the experimentally measured values...
May 25, 2017: Proteins
https://www.readbyqxmd.com/read/28547661/targeting-sclerostin-in-postmenopausal-osteoporosis-focus-on-romosozumab-and-blosozumab
#2
Ian R Reid
Most current treatments for osteoporosis inhibit bone resorption and reduce total fracture numbers by about one-quarter. The identification of the osteocytic protein sclerostin as a potent regulator of bone turnover and bone density has led to the development of a new therapeutic class-agents that inhibit sclerostin activity, resulting in increased bone formation and reduced bone resorption. Romosozumab and blosozumab are monoclonal antibodies that bind to sclerostin, reducing its inhibition of Wnt signaling...
May 25, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/28546457/amino-acid-homeostasis-and-signalling-in-mammalian-cells-and-organisms
#3
REVIEW
Stefan Bröer, Angelika Bröer
Cells have a constant turnover of proteins that recycle most amino acids over time. Net loss is mainly due to amino acid oxidation. Homeostasis is achieved through exchange of essential amino acids with non-essential amino acids and the transfer of amino groups from oxidised amino acids to amino acid biosynthesis. This homeostatic condition is maintained through an active mTORC1 complex. Under amino acid depletion, mTORC1 is inactivated. This increases the breakdown of cellular proteins through autophagy and reduces protein biosynthesis...
May 25, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28541049/synthesis-and-photophysical-and-photocatalytic-properties-of-a-highly-fluorinated-and-durable-phthalocyanine-peptide-bioconjugate-for-potential-theranostic-applications
#4
Erik N Carrión, Jenyffer Santiago, David Sabatino, Sergiu M Gorun
The functionalized, asymmetric fluoro-fluoroalkyl scaffold F48H7COOHPcZn (3) was used to prepare F48H7COOPcZn-6-amino-hexanoate-CTVALPGGYVRVC (5), a Pep42 peptide bioconjugate envisioned for photodynamic therapy, which can specifically target the GRP78 chaperone protein overexpressed and exclusively localized on some cancer cell surfaces. The analogous F48H7COOHPcCu (4) has also been prepared, and its single-crystal X-ray structure was elucidated. Despite reduced steric hindrance relative to the nonfunctionalized, single-site complexes of the F64Pc scaffold, no aggregation was detected in solution via UV-vis spectroscopy, for either 3, 4, or 5, consistent with the lack of π stacking observed for the crystalline 4...
May 25, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28539825/effects-of-c-reactive-protein-on-the-expression-of-matrix-metalloproteinases-and-their-inhibitors-via-fc%C3%AE-receptors-on-3t3-l1-adipocytes
#5
Kumiko Nakai, Hideki Tanaka, Kazuhiro Yamanaka, Yumi Takahashi, Fumiko Murakami, Rieko Matsuike, Jumpei Sekino, Natsuko Tanabe, Toyoko Morita, Yoji Yamazaki, Takayuki Kawato, Masao Maeno
The association between obesity and inflammation is well documented in epidemiological studies. Proteolysis of extracellular matrix (ECM) proteins is involved in adipose tissue enlargement, and matrix metalloproteinases (MMPs) collectively cleave all ECM proteins. Here, we examined the effects of C-reactive protein (CRP), an inflammatory biomarker, on the expression of MMPs and tissue inhibitors of metalloproteinases (TIMPs), which are natural inhibitors of MMPs, in adipocyte-differentiated 3T3-L1 cells. We analyzed the expression of Fcγ receptor (FcγR) IIb and FcγRIII, which are candidates for CRP receptors, and the effects of anti-CD16/CD32 antibodies, which can act as FcγRII and FcγRIII blockers on CRP-induced alteration of MMP and TIMP expression...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28539410/leishmania-donovani-restricts-mitochondrial-dynamics-to-enhance-mirnp-stability-and-target-rna-repression-in-host-macrophages
#6
Yogaditya Chakrabarty, Suvendra N Bhattacharyya
microRNAs (miRNA), the tiny regulatory RNAs, form complex with Argonaute (Ago) proteins and inhibit gene expression in metazoan cells. While studying parasite invaded macrophages, we have identified a unique mode of gene regulation, where the parasite Leishmania donovani (Ld) causes mitochondrial depolarization, reduces mitochondrial dynamics and restricts turnover of cellular microRNA ribonucleoprotein (miRNP) complexes in infected host cells. This leads to increased stability of miRNPs along with elevated level of Ago2 bound cytokine mRNA in Ld infected macrophages...
May 24, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28539401/transmembrane-helix-hydrophobicity-is-an-energetic-barrier-during-the-retrotranslocation-of-integral-membrane-erad-substrates
#7
Christopher J Guerriero, Karl-Richard Reutter, Andrew A Augustine, G Michael Preston, Kurt F Weiberth, Timothy D Mackie, Hillary C Cleveland-Rubeor, Neville P Bethel, Keith M Callenberg, Kunio Nakatsukasa, Michael Grabe, Jeffrey L Brodsky
Integral membrane proteins fold inefficiently and are susceptible to turnover via the endoplasmic reticulum-associated degradation (ERAD) pathway. During ERAD, misfolded proteins are recognized by molecular chaperones, polyubiquitinated, and retrotranslocated to the cytoplasm for proteasomal degradation. Although many aspects of this pathway are defined, how transmembrane helices (TMHs) are removed from the membrane and into the cytoplasm prior to degradation is poorly understood. In this study, we asked whether the hydrophobic character of a TMH acts as an energetic barrier to retrotranslocation...
May 24, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28538170/yap-regulates-actin-dynamics-through-arhgap29-and-promotes-metastasis
#8
Yiting Qiao, Jianxiang Chen, Ying Bena Lim, Megan Louise Finch-Edmondson, Veerabrahma Pratap Seshachalam, Lei Qin, Tingting Jiang, Boon Chuan Low, Himanshu Singh, Chwee Teck Lim, Marius Sudol
Yes-associated protein (YAP) is regulated by mechanical cues via the interaction of the Hippo pathway with cytoskeleton. Previous studies showed that YAP plays a role in regulating the actomyosin network by suppressing Rho GTPase in medaka fish. Here, we identify Rho GTPase activating protein 29 (ARHGAP29) as a transcriptional target of YAP in a human gastric cancer cell line. YAP promotes the expression of ARHGAP29 to suppress the RhoA-LIMK-cofilin pathway, destabilizing F-actin. The overexpression of YAP causes cytoskeletal rearrangement by altering the dynamics of F-actin/G-actin turnover, thus promoting migration...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28535250/evidence-for-the-deregulation-of-protein-turnover-pathways-in-atm-deficient-mouse-cerebellum-an-organotypic-study
#9
Catherine D Kim, Ryan E Reed, Meredith A Juncker, Zhide Fang, Shyamal D Desai
Interferon-stimulated gene 15 (ISG15), an antagonist of the ubiquitin pathway, is elevated in cells and brain tissues obtained from ataxia telangiectasia (A-T) patients. Previous studies reveal that an elevated ISG15 pathway inhibits ubiquitin-dependent protein degradation, leading to activation of basal autophagy as a compensatory mechanism for protein turnover in A-T cells. Also, genotoxic stress (ultraviolet [UV] radiation) deregulates autophagy and induces aberrant degradation of ubiquitylated proteins in A-T cells...
May 23, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28534027/current-concepts-and-unresolved-questions-in-dietary-protein-requirements-and-supplements-in-adults
#10
REVIEW
Stuart M Phillips
Protein needs for otherwise healthy individuals older than 19 years are defined by the recommended dietary allowance (RDA) at 0.80 g protein/kg/day. There is no recommendation in the current RDA for subpopulations of older adults or people in various pathological situations. Despite the lack of a separate recommendation, there exists a growing body of evidence that is strongly suggestive of an increased need and/or benefit for protein in older persons. That is, intakes beyond the RDA are, in older persons, associated with benefits...
2017: Frontiers in Nutrition
https://www.readbyqxmd.com/read/28532758/the-kelch-surprise-klhl24-%C3%A2-a%C3%A2-new%C3%A2-player-in-the-pathogenesis-of%C3%A2-skin-fragility
#11
Cristina Has
A new protein, kelch-like 24, has recently been associated with a distinct subtype of epidermolysis bullosa simplex, a heterogeneous group of disorders associated with mechanical fragility of epidermal keratinocytes. All mutations involve the translation initiation codon and lead to a degradation-resistant N-terminally truncated kelch-like 24. Kelch-like 24 appears to be involved in the turnover of intermediated filaments, in particular of keratin 14, in keratinocytes.
June 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28532242/antioxidant-supplementation-a-linchpin-in-radiation-induced-enteritis
#12
Mumtaz Anwar, Shabeer Ahmad, Reyhan Akhtar, Akhtar Mahmood, Safrun Mahmood
Radiation enteritis is one of the most feared complications of abdominal and pelvic regions. Thus, radiation to abdominal or pelvic malignancies unavoidably injures the intestine. Because of rapid cell turnover, the intestine is highly sensitive to radiation injury, which is the limiting factor in the permissible dosage of irradiation. Bowel injuries such as fistulas, strictures, and chronic malabsorption are potentially life-threatening complications and have an impact on patient quality of life. The incidence of radiation enteritis is increasing because of the current trend of combined chemotherapy and radiation...
January 1, 2017: Technology in Cancer Research & Treatment
https://www.readbyqxmd.com/read/28532231/external-coincidence-model-for-hypocotyl-thermomorphogenesis
#13
Young-Joon Park, Chung-Mo Park
High but nonstressful temperatures profoundly affect plant growth and developmental processes, termed thermomorphogenesis. Thermo-induced hypocotyl elongation is a typical thermomorphogenic trait, which contributes to cooling plant organs. It is known that external light signals and the circadian clock coordinate rhythmic hypocotyl growth. However, it was unclear how light, temperature, and circadian rhythms are harmonized during hypocotyl thermomorphogenesis. We have recently demonstrated that the E3 ubiquitin ligase CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) is activated at warm temperatures...
May 22, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28531309/effect-of-antiretroviral-therapy-on-bone-and-renal-health-in-young-adults-infected-with-hiv-in-early-life
#14
Aylin B Unsal, Aviva S Mattingly, Sara E Jones, Julia B Purdy, James C Reynolds, Jeffrey B Kopp, Rohan Hazra, Colleen M Hadigan
Context: HIV antiretroviral (ARV) therapy is associated with renal and bone toxicity, but little is known about the potential cumulative effects in adults exposed to ARVs from birth. Objective: To prospectively evaluate renal and bone health in young adults with lifelong HIV and extensive ARV exposure. Design: Cross-sectional comparison of bone mineral density (BMD by dual-energy X-ray absorptiometry), bone turnover and renal function in young adults infected with HIV in early life (n=65) to matched healthy controls (n=23) and longitudinal evaluation (mean follow-up 4...
May 22, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28531263/in-vivo-dynamics-of-the-cortical-actin-network-revealed-by-fast-scanning-atomic-force-microscopy
#15
Yanshu Zhang, Aiko Yoshida, Nobuaki Sakai, Yoshitsugu Uekusa, Masahiro Kumeta, Shige H Yoshimura
Together with lamellipodia and stress fibers, a dynamic network of actin filaments in the cell cortex plays a major role in the maintenance of cell morphology and motility. In contrast to lamellipodia, which have been well studied in various motile cells, the dynamics of actin filaments in the cell cortex have not yet been clarified due to a lack of proper imaging techniques. Here, we utilized high-speed atomic force microscopy for live-cell imaging and analyzed cortical actin dynamics in living cells. We successfully measured the polymerization rate and the frequency of filament synthesis in living COS-7 cells, and examined the associated effects of various inhibitors and actin-binding proteins...
May 20, 2017: Microscopy
https://www.readbyqxmd.com/read/28529520/katanin-1-is-essential-for-embryogenesis-and-seed-formation-in-arabidopsis
#16
Ivan Luptovčiak, Despina Samakovli, George Komis, Jozef Šamaj
Cytoskeletal remodeling has a fundamental role, especially during transitional developmental stages when cells rapidly adopt new forms and roles, like gametogenesis, fertilization and concomitant embryogenesis and seed formation. KATANIN 1, a microtubule severing protein, fulfills a major regulatory mechanism of dynamic microtubule turnover in eukaryotes. Herein, we show that three well-established KATANIN 1 mutants, fra2, lue1 and ktn1-2 collectively display lower fertility and seed set in Arabidopsis. These lower fertility and seed set rates of fra2, lue1 and ktn1-2 mutants were correlated to abnormalities in the development of embryo proper and seed...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28528289/platelet-hyperactivation-apoptosis-and-hypercoagulability-in-patients-with-acute-pulmonary-embolism
#17
Samin Rezania, Michael A Puskarich, Daniela N Petrusca, Evandro M Neto-Neves, Matthew T Rondina, Jeffrey A Kline
Changes in systemic redox balance can alter platelet activation and aggregation. Acute pulmonary embolism (PE) is a systematic inflammatory disease associated with mechanical shear stress, increased thrombin, catecholamines, serotonin and hemolysis, which cumulatively can hyperactivate platelets and accelerate their turnover. We tested the hypothesis that platelets from patients with moderately severe PE will show hyperstimulation and a pre-apoptotic phenotype associated with microparticles (MPs) in plasma...
May 13, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28528213/optimal-electrostatic-interactions-between-substrate-and-protein-are-essential-for-radical-chemistry-in-ornithine-4-5-aminomutase
#18
Caitlyn Makins, Douglas A Whitelaw, Michael McGregor, Alix Petit, Robert G Mothersole, Kathleen E Prosser, Kirsten R Wolthers
Ornithine 4,5-aminomutase (OAM) from Clostridium sticklandii is an adenosylcobalamin (AdoCbl) and pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes a 1,2-amino shift, interconverting D-ornithine and 2S, 4R-diaminopentanoate. The reaction occurs via a radical-based mechanism whereby a PLP-bound substrate radical undergoes intramolecular isomerization via an azacyclopropylcarbinyl radical intermediate. Herein, we investigated the catalytic role of active site residues that form non-covalent interactions with PLP and/or substrate, D-ornithine...
May 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28526562/new-intracellular-activities-of-matrix-metalloproteinases-shine-in-the-moonlight
#19
REVIEW
Parker G Jobin, Georgina S Butler, ChristopherM Overall
Adaption of a single protein to perform multiple independent functions facilitates functional plasticity of the proteome allowing a limited number of protein-coding genes to perform a multitude of cellular processes. Multifunctionality is achievable by post-translational modifications and by modulating subcellular localization. Matrix metalloproteinases (MMPs), classically viewed as degraders of the extracellular matrix (ECM) responsible for matrix protein turnover, are more recently recognized as regulators of a range of extracellular bioactive molecules including chemokines, cytokines, and their binders...
May 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28524452/subtilisin-like-proteases-in-plant-defence-the-past-the-present-and-beyond
#20
REVIEW
Joana Figueiredo, Marta Sousa Silva, Andreia Figueiredo
Subtilisin-like proteases (or subtilases) are a very diverse family of serine peptidases present in many organisms, but mostly in plants. With a broad spectrum of biological functions ranging from protein turnover and plant development to interactions with the environment, subtilases have been gaining more attention for their involvement in plant defence responses against the most diverse pathogens. On the last 5 years, the number of published studies associating plant subtilases with pathogen resistance and plant immunity increased tremendously...
May 19, 2017: Molecular Plant Pathology
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