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https://www.readbyqxmd.com/read/27923209/recognition-of-ubiquitinated-nucleosomes
#1
REVIEW
Michael T Morgan, Cynthia Wolberger
Histone ubiquitination plays a non-degradative role in regulating transcription and the DNA damage response. A mechanistic understanding of this chromatin modification has lagged that of small histone modifications because of the technical challenges in preparing ubiquitinated nucleosomes. The recent structure of the DUB module of the SAGA coactivator complex bound to a nucleosome containing monoubiquitinated H2B has provided the first view of how specialized subunits target this enzyme to its substrate. Single particle electron microscopy of the intact SAGA coactivator suggests how the DUB module and histone acetyltransferase module engage a nucleosomal substrate...
December 3, 2016: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/27922847/apolipoprotein-e-metabolism-and-functions-in-brain-and-its-role-in-alzheimer-s-disease
#2
Fan Liao, Hyejin Yoon, Jungsu Kim
PURPOSE OF REVIEW: APOE4 genotype is the strongest genetic risk factor for Alzheimer's disease. Prevailing evidence suggests that amyloid β plays a critical role in Alzheimer's disease. The objective of this article is to review the recent findings about the metabolism of apolipoprotein E (ApoE) and amyloid β and other possible mechanisms by which ApoE contributes to the pathogenesis of Alzheimer's disease. RECENT FINDINGS: ApoE isoforms have differential effects on amyloid β metabolism...
December 5, 2016: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/27922670/downregulation-of-laptm5-suppresses-cell-proliferation-and-viability-inducing-cell-cycle-arrest-at-g0-g1-phase-of-bladder-cancer-cells
#3
Liang Chen, Gang Wang, Yi Luo, Yongzhi Wang, Conghua Xie, Wei Jiang, Yu Xiao, Guofeng Qian, Xinghuan Wang
Our transcriptome analysis revealed in bladder cancer (BCa) tissues a significant induction of lysosomal-associated multispanning membrane protein 5 (LAPTM5), a lysosomal membrane protein preferentially expressing in immune cells and hematopoietic cells. Transportation of LAPTM5 from Golgi to lysosome could be inhibited by deficiency of Nedd4, a key member of E3 ubiquitin ligase family overexpressing in invasive BCa and promoting its progression. Therefore, we hypothesize that LAPTM5 may be closely correlated with BCa tumorigenesis...
December 5, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27922612/the-intricate-dance-of-post-translational-modifications-in-the-rhythm-of-life
#4
REVIEW
Arisa Hirano, Ying-Hui Fu, Louis J Ptáček
Endogenous biological rhythms with approximately 24-h periodicity are generated by the circadian clock, in which clock genes coordinate with one another and form a transcriptional-translational negative feedback loop. The precision of the circadian clock is further regulated by multiple post-translational modifications (PTMs), including phosphorylation, ubiquitination, acetylation and SUMOylation. Here, we review current understanding of the regulatory mechanisms of the core clock proteins by PTMs in the mammalian circadian clock...
December 6, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27922495/toxic-and-endocrine-myopathies
#5
Hans D Katzberg, Charles D Kassardjian
PURPOSE OF REVIEW: This article discusses the clinical features, pathophysiology, and management of toxic and endocrine myopathies. RECENT FINDINGS: Early detection and expeditious correction of metabolic disturbances in endocrinopathies such as Cushing syndrome, thyroid and parathyroid diseases, and acromegaly can minimize and prevent neurologic complications including myopathy. Recently proposed mechanisms of injury in patients with critical illness myopathy include inhibition of protein synthesis, mitochondrial dysfunction, disruption of the ubiquitin-proteasome system, oxidative stress, and disruption of intramuscular calcium homeostasis, which can cause a myosin-loss myopathy...
December 2016: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/27922451/direct-screening-for-chromatin-status-on-dna-barcodes-in-yeast-delineates-the-regulome-of-h3k79-methylation-by-dot1
#6
Hanneke Vlaming, Thom M Molenaar, Tibor van Welsem, Deepani W Poramba-Liyanage, Desiree E Smith, Arno Velds, Liesbeth Hoekman, Tessy Korthout, Sjoerd Hendriks, Af Maarten Altelaar, Fred van Leeuwen
Given the frequent misregulation of chromatin in cancer, it is important to understand the cellular mechanisms that regulate chromatin structure. However, systematic screening for epigenetic regulators is challenging and often relies on laborious assays or indirect reporter read-outs. Here we describe a strategy, Epi-ID, to directly assess chromatin status in thousands of mutants. In Epi-ID, chromatin status on DNA barcodes is interrogated by chromatin immunoprecipitation followed by deep sequencing, allowing for quantitative comparison of many mutants in parallel...
December 6, 2016: ELife
https://www.readbyqxmd.com/read/27920276/studies-of-recombinant-twa1-reveal-constitutive-dimerisation
#7
Ore Francis, Genevieve E Baker, Paul R Race, Josephine C Adams
The mammalian muskelin/RanBP9/CTLH complex and the S. cerevisiae GID complex are large, multi-protein complexes that each contain a RING E3 ubiquitin ligase. The yeast GID complex acts to degrade a key enzyme of gluconeogenesis, fructose 1,6-bisphosphatase, under conditions of abundant fermentable carbon sources. However, the assembly and functions of the mammalian complex remain poorly understood. A striking feature of these complexes is the presence of multiple proteins that contain contiguous lissencephaly-1 homology (LisH), C-terminal to LisH (CTLH) and C-terminal CT11-RanBP9 (CRA) domains...
December 5, 2016: Bioscience Reports
https://www.readbyqxmd.com/read/27920251/a-homeostatic-shift-facilitates-endoplasmic-reticulum-proteostasis-through-transcriptional-integration-of-proteostatic-stress-response-pathways
#8
Liam Baird, Tadayuki Tsujita, Eri Kobayashi, Ryo Funayama, Takeshi Nagashima, Keiko Nakayama, Masayuki Yamamoto
Eukaryotic cells maintain protein homeostasis through the activity of multiple basal and inducible systems, which function in concert to allow cells to adapt to a wide range of environmental conditions. Whilst the transcriptional programs regulating individual pathways have been studied in detail, it is not known how the different pathways are transcriptionally integrated such that a deficiency in one pathway can be compensated by a change in an auxiliary response. One such pathway that plays an essential role in many proteostasis responses is the ubiquitin-proteasome system (UPS), which functions to degrade damaged, unfolded or short half-life proteins...
December 5, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27919820/tnf-%C3%AE-and-cancer-cachexia-molecular-insights-and-clinical-implications
#9
REVIEW
Hetal J Patel, Bhoomika M Patel
Cancer cachexia characterized by a chronic wasting syndrome, involves skeletal muscle loss and adipose tissue loss and resistance to conventional nutritional support. Cachexia is responsible for the reduction in quality and length of life of cancer patients. It also decreases the muscle strength of the patients. The pro-inflammatory and pro-cachectic factors produced by the tumor cells have important role in genesis of cachexia. A number of pro-inflammatory cytokines, like interleukin-1 (IL-1), IL-6, tumor necrosis factor- alpha (TNF-α) may have important role in the pathological mechanisms of cachexia in cancer...
December 2, 2016: Life Sciences
https://www.readbyqxmd.com/read/27919796/the-bad-seed-gardener-deubiquitinases-in-the-cancer-stem-cell-signaling-network-and-therapeutic-resistance
#10
REVIEW
Guan-Zhong Qiu, Wei Sun, Ming-Zhu Jin, Jing Lin, Pei-Gang Lu, Wei-Lin Jin
Tumors are comprised of highly heterogeneous populations of cells, of which only a small subset of stem-like cells possess the ability to regenerate tumors in vivo. These rare cancer stem cells (CSCs) have been regarded as the "bad seeds" accounted for tumor initiation, progression, metastasis, relapse and therapeutic resistance. CSC-targeted therapy seems to be a better avenue for radical cure of cancer. Deubiquitinases (DUBs), specifically disassembling ubiquitin chains, have been demonstrated to play an important role in rigidly maintaining the balance between ubiquitination and deubiquitination for protein quality control and homeostasis in normal circumstances...
December 2, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27919694/neuron-specific-sumo-knockdown-suppresses-global-gene-expression-response-and-worsens-functional-outcome-after-transient-forebrain-ischemia-in-mice
#11
Lin Zhang, Xiaozhi Liu, Huaxin Sheng, Shuai Liu, Ying Li, Julia Q Zhao, David S Warner, Wulf Paschen, Wei Yang
Small ubiquitin-like modifier (SUMO) conjugation (SUMOylation) plays key roles in neurologic function in health and disease. Neuronal SUMOylation is essential for emotionality and cognition, and this pathway is dramatically activated in post-ischemic neurons, a neuroprotective response to ischemia. It is also known from cell culture studies that SUMOylation modulates gene expression. However, it remains unknown how SUMOylation regulates neuronal gene expression in vivo, in the physiologic state and after ischemia, and modulates post-ischemic recovery of neurologic function...
December 2, 2016: Neuroscience
https://www.readbyqxmd.com/read/27919079/receptor-usage-dictates-hiv-1-restriction-by-human-trim5%C3%AE-in-dendritic-cell-subsets
#12
Carla M S Ribeiro, Ramin Sarrami-Forooshani, Laurentia C Setiawan, Esther M Zijlstra-Willems, John L van Hamme, Wikky Tigchelaar, Nicole N van der Wel, Neeltje A Kootstra, Sonja I Gringhuis, Teunis B H Geijtenbeek
The most prevalent route of HIV-1 infection is across mucosal tissues after sexual contact. Langerhans cells (LCs) belong to the subset of dendritic cells (DCs) that line the mucosal epithelia of vagina and foreskin and have the ability to sense and induce immunity to invading pathogens. Anatomical and functional characteristics make LCs one of the primary targets of HIV-1 infection. Notably, LCs form a protective barrier against HIV-1 infection and transmission. LCs restrict HIV-1 infection through the capture of HIV-1 by the C-type lectin receptor Langerin and subsequent internalization into Birbeck granules...
December 7, 2016: Nature
https://www.readbyqxmd.com/read/27917940/ubiquitin-ligase-nedd4-regulates-ppar%C3%AE-stability-and-adipocyte-differentiation-in-3t3-l1-cells
#13
Jing Jing Li, Ruishan Wang, Rati Lama, Xinjiang Wang, Z Elizabeth Floyd, Edwards A Park, Francesca-Fang Liao
Peroxisome proliferator-activated receptor-γ (PPARγ) is a ligand-activated nuclear receptor which controls lipid and glucose metabolism. It is also the master regulator of adipogenesis. In adipocytes, ligand-dependent PPARγ activation is associated with proteasomal degradation; therefore, regulation of PPARγ degradation may modulate its transcriptional activity. Here, we show that neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4), an E3 ubiquitin ligase, interacts with the hinge and ligand binding domains of PPARγ and is a bona fide E3 ligase for PPARγ...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27917893/new-insights-into-molecular-organization-of-human-neuraminidase-1-transmembrane-topology-and-dimerization-ability
#14
Pascal Maurice, Stéphanie Baud, Olga V Bocharova, Eduard V Bocharov, Andrey S Kuznetsov, Charlotte Kawecki, Olivier Bocquet, Beatrice Romier, Laetitia Gorisse, Maxime Ghirardi, Laurent Duca, Sébastien Blaise, Laurent Martiny, Manuel Dauchez, Roman G Efremov, Laurent Debelle
Neuraminidase 1 (NEU1) is a lysosomal sialidase catalyzing the removal of terminal sialic acids from sialyloconjugates. A plasma membrane-bound NEU1 modulating a plethora of receptors by desialylation, has been consistently documented from the last ten years. Despite a growing interest of the scientific community to NEU1, its membrane organization is not understood and current structural and biochemical data cannot account for such membrane localization. By combining molecular biology and biochemical analyses with structural biophysics and computational approaches, we identified here two regions in human NEU1 - segments 139-159 (TM1) and 316-333 (TM2) - as potential transmembrane (TM) domains...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27917682/the-preclinical-discovery-and-development-of-bortezomib-for-the-treatment-of-mantle-cell-lymphoma
#15
Richard Arkwright, Tri Minh Pham, Jeffrey A Zonder, Q Ping Dou
Introduction- Mantle cell lymphoma (MCL) is an incurable, often aggressive B-cell malignancy. Bortezomib (BTZ), the 20S proteasome inhibitor was originally developed and approved for treatment of relapsed refractory multiple myeloma, and subsequently approved for treatment of MCL. BTZ's single-agent activity induces clinical responses in approximately one-third of relapsed MCL patients. BTZ-containing combination therapies have further improved the quality and duration of clinical responses compared to standard chemotherapies in previously untreated MCL patients...
December 3, 2016: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/27916606/fbx8-is-a-metastasis-suppressor-downstream-of-mir-223-and-targeting-mtor-for-degradation-in-colorectal-cancer
#16
F F Wang, X J Zhang, Y R Yan, X H Zhu, J Yu, Y Ding, J L Hu, W J Zhou, Z C Zeng, W T Liao, Y Q Ding, L Liang
F-box proteins are critical components of the SKP1-CUL1-F-box (SCF) E3 ubiquitin ligases and involved in the ubiquitin-dependent proteolytic pathway. Dysregulation of F-box protein-mediated proteolysis often leads to human malignancies. F-box only protein 8 (FBX8), a novel component of F-box proteins, is down-regulated in several tumors and closely correlates with tumor progression. However, little is known about its function, regulatory mechanisms and substrates in the progression of colorectal cancer (CRC)...
December 1, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27916542/the-role-of-the-ubiquitin-proteasome-system-in-the-memory-process
#17
REVIEW
Philomena Z Y Lip, Marilene Demasi, Diego Bonatto
Quite intuitive is the notion that memory formation and consolidation is orchestrated by protein synthesis because of the synaptic plasticity necessary for those processes. Nevertheless, recent advances have begun accumulating evidences of a high requirement for protein degradation on the molecular mechanisms of the memory process in the mammalian brain. Because degradation determines protein half-life, degradation has been increasingly recognized as an important intracellular regulatory mechanism. The proteasome is the main player in the degradation of intracellular proteins...
December 1, 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27916521/structural-insights-into-linear-tri-ubiquitin-recognition-by-a20-binding-inhibitor-of-nf-%C3%AE%C2%BAb-abin-2
#18
Shan-Meng Lin, Su-Chang Lin, Jhen-Yi Hong, Tsung-Wei Su, Bai-Jiun Kuo, Wei-Hsin Chang, Yi-Fan Tu, Yu-Chih Lo
Recognition of linear polyubiquitin by specific ubiquitin-binding proteins plays an important role in mediating nuclear factor-κB (NF-κB) signaling. A20 binding proteins, ABINs, recognize linear polyubiquitin and A20 through UBAN and AHD1, respectively, for the inhibition of NF-κB activation. Here we report the crystal structure of the AHD1-UBAN fragment of ABIN2 in complex with linear tri-ubiquitin, which reveals a 2:1 stoichiometry of the complex. Structural analyses together with mutagenesis, pull-down, and isothermal titration calorimetry assays show that the hABIN2:tri-ubiquitin interaction is mainly through the primary ubiquitin-binding site, and also through the secondary ubiquitin-binding site under a high local protein concentration...
November 24, 2016: Structure
https://www.readbyqxmd.com/read/27916088/-hyperoxia-induces-aecii-apoptosis-of-premature-rats-by-reducing-the-activity-of-20s-proteasome
#19
Yanyu Zhang, Hongyan Lu, Huimin Ju, Ming Chang, Qiuxia Wang, Qiang Zhang
Objective To establish a hyperoxia-exposed cell damage model of primary cultured premature rat alveolar type II epithelial cells (AECIIs) and investigate the effect of hyperoxia on ubiquitinated protein degradation and apoptosis of AECIIs. Methods Primary cultured premature rat AECIIs in vitro were divided into air group and hyperoxia group, which were exposed to air and 950 mL/L O2, respectively. After 24-, 48- and 72-hour exposure, isothiocyanate-labeled annexinV/propidium iodide (annexinV-FITC/PI) double staining combined with flow cytometry was utilized to detect the apoptosis of AECIIs...
December 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/27915976/strategies-to-strike-survival-networks-in-cancer
#20
Marzia Pennati, Graziella Cimino-Reale, Laura Gatti, Giuliana Cassinelli
The machinery that maintains cellular and tissue homeostasis in a healthy individual is recruited and hijacked by cancer cells to support tumor growth and progression. Activation of often unpredictable alternative or complementary signaling pathways allows cancer cells to bypass the intrinsic self-destructive machinery and the limited replicative potential present in every cell for correct homeostasis maintenance. Therefore, evasion/resistance to apoptosis/cell death, self-sufficiency in growth/survival signals, and limitless replicative potential remain undoubted hallmarks of cancer, contributing to drug resistance...
2016: Critical Reviews in Oncogenesis
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