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Journal of Biological Chemistry

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https://www.readbyqxmd.com/read/28446612/cdk4-is-degraded-by-apc-c-in-mitosis-and-reaccumulates-in-early-g1-phase-to-initiate-a-new-cell-cycle-in-hela-cells
#1
Huabo Chen, Xiaowei Xu, Guopeng Wang, Boyan Zhang, Gang Wang, Guangwei Xin, Junjun Liu, Qing Jiang, Hongyin Zhang, Chuanmao Zhang
CDK4 regulates G1-S phase transition in mammalian cell cycle by phosphorylating retinoblastoma family proteins. However, the mechanism underlying the regulation of CDK4 activity is not fully understood. Here, we show that CDK4 protein is degraded by APC/C during metaphase-anaphase (M-A) transition in HeLa cells, whereas its main regulator cyclin D1 remains intact but is sequestered in cytoplasm. CDK4 protein reaccumulates in the following G1 phase, and shuttles between the nucleus and the cytoplasm to facilitate the nuclear import of cyclin D1...
April 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28446611/unraveling-amino-acid-residues-critical-for-allosteric-potentiation-of-%C3%AE-4-3-%C3%AE-2-2-type-nicotinic-acetylcholine-receptor-responses
#2
Ze-Jun Wang, Farah Deba, Tasnim S Mohamed, David C Chiara, Kara Ramos, Ayman K Hamouda
Neuronal nicotinic acetylcholine receptors (nAChRs) are promising drug targets to manage several neurological disorders and nicotine addiction. Growing evidence indicates that positive allosteric modulators (PAMs) of nAChRs improve pharmacological specificity by binding to unique sites present only in a subpopulation of nAChRs. Furthermore, nAChR PAMs such as NS9283 and CMPI have been shown to potentiate responses of (α4)3(β2)2 but not (α4)2(β2)3 nAChR isoforms. This selective potentiation underlines that the α4:α4 interface, which is present only in the (α4)3(β2)2 nAChR, is an important and promising drug target...
April 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28446610/conformational-changes-at-cytoplasmic-inter-subunit-interactions-control-kir-channel-gating
#3
Shizhen Wang, William F Borschel, Sarah Heyman, Phillip Hsu, Colin G Nichols
The defining structural feature of inward-rectifier potassium (Kir) channels is the unique Kir cytoplasmic domain. Recently, we have shown that salt bridges located at the cytoplasmic domain subunit interfaces (CD-Is) of eukaryotic Kir channels control channel gating via stability of a novel inactivated closed state. The cytoplasmic domains of prokaryotic and eukaryotic Kir channels show similar conformational rearrangements to the common gating ligand, phosphatidylinositol bisphosphate (PIP2), although this exhibits opposite coupling to opening and closing transitions...
April 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28446609/glycosylation-of-the-core-of-the-hiv-1-envelope-subunit-protein-gp120-is-not-required-for-native-trimer-formation-or-viral-infectivity
#4
Ujjwal Rathore, Piyali Saha, Sannula Kesavardhana, Aditya Arun Kumar, Rohini Datta, Sivasankar Devanarayanan, Raksha Das, John R Mascola, Raghavan Varadarajan
The gp120 subunit of HIV-1 envelope (Env) protein is heavily glycosylated at approximately 25 glycosylation sites, of which ~7-8 are located in the V1/V2 and V3 variable loops and the others in the remaining core gp120 region. Glycans partially shield Env from recognition by the host immune system and also are believed to be indispensable for proper folding of gp120 and for viral infectivity. Previous attempts to alter glycosylation sites in Env typically involved mutating the glycosylated asparagine residues to structurally similar glutamines or to alanines...
April 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28446608/model-enabled-gene-search-megs-allows-fast-and-direct-discovery-of-enzymatic-and-transport-gene-functions-in-the-marine-bacterium-vibrio-fischeri
#5
Shu Pan, Kiel Nikolakakis, Paul A Adamczyk, Min Pan, Edward G Ruby, Jennifer L Reed
While genomes can be rapidly sequenced, the functions of many genes are incompletely or erroneously annotated because of a lack of experimental evidence or prior functional knowledge in sequence databases. To address this weakness, we describe here a model-enabled gene search (MEGS) approach that (i) identifies metabolic functions either missing from an organism's genome annotation or incorrectly assigned to an ORF, by using discrepancies between metabolic model predictions and experimental culturing data; (ii) designs functional selection experiments for these specific metabolic functions; and (iii) selects a candidate gene(s) responsible for these functions from a genomic library and directly interrogates this gene's function experimentally...
April 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28446607/juvenile-hormone-and-its-receptor-methoprene-tolerant-promote-ribosomal-biogenesis-and-vitellogenesis-in-the-aedes-aegypti-mosquito
#6
Jia-Lin Wang, Tusar T Saha, Yang Zhang, Changyu Zhang, Alexander S Raikhel
Juvenile hormone (JH) controls many biological activities in insects, including development, metamorphosis and reproduction. In the Aedes aegypti mosquito, a vector of Dengue, Yellow fever, Chikungunya and Zika viruses, the metabolic tissue, the fat body, which is an analogue of the vertebrate liver, produces yolk proteins (YPs) for developing oocytes. JH is important for the fat body to acquire competence for YP production. However, the molecular mechanisms of how JH promotes mosquito reproduction are not completely understood...
April 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28446606/the-beh%C3%A3-et-s-disease-associated-variant-of-the-aminopeptidase-erap1-shapes-a-low-affinity-hla-b-51-peptidome-by-differential-subpeptidome-processing
#7
Pablo Guasp, Eilon Barnea, M Francisca González-Escribano, Anaïs Jiménez-Reinoso, José R Regueiro, Arie Admon, José A López de Castro
A low activity variant of endoplasmic reticulum aminopeptidase 1 (ERAP1), Hap10, is associated with the autoinflammatory Behcet s disease (BD) in epistasis with HLA-B*51, which is the main risk factor for this disorder. The role of Hap10 in BD pathogenesis is unknown. We sought to define the effects of Hap10 on the HLA-B*51 peptidome and to distinguish these effects from those due to HLA-B*51 polymorphisms unrelated to disease. The peptidome of the BD-associated HLA-B*51:08 subtype expressed in a Hap10-positive cell line was isolated, characterized by mass spectrometry, and compared with the HLA-B*51:01 peptidome from cells expressing more active ERAP1 allotypes...
April 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28446605/crispr-cas9-mediated-gene-knockout-screens-and-target-identification-via-whole-genome-sequencing-uncover-host-genes-required-for-picornavirus-infection
#8
Heon Seok Kim, Kyungjin Lee, Sangsu Bae, Jeongbin Park, Chong-Kyo Lee, Meehyein Kim, Eunji Kim, Minju Kim, Seokjoong Kim, Chonsaeng Kim, Jin-Soo Kim
Several groups have used genome-wide libraries of lentiviruses encoding small-guide RNAs (sgRNAs) for genetic screens. In most cases, sgRNA expression cassettes are integrated into cells by using lentiviruses, and target genes are statistically estimated by the readout of sgRNA sequences after targeted sequencing. We present a new virus-free method for human gene-knockout screens using a genome-wide library of CRISPR/Cas9 sgRNAs based on plasmids, and target gene identification via whole-genome sequencing (WGS) confirming authentic mutations rather than statistical estimating through targeted amplicon sequencing...
April 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28446604/cell-cycle-dependent-regulation-of-greatwall-kinase-by-protein-phosphatase-1-and-regulatory-subunit-3b
#9
Dapeng Ren, Laura A Fisher, Jing Zhao, Ling Wang, Byron C Williams, Michael L Goldberg, Aimin Peng
Greatwall (Gwl) kinase plays an essential role in regulation of mitotic entry and progression. Mitotic activation of Gwl requires both cyclin-dependent kinase 1 (CDK1)-dependent phosphorylation and its autophosphorylation at an evolutionarily-conserved serine residue near the carboxyl-terminus (Ser-883 in Xenopus). In this study we show that Gwl associates with protein phosphatase 1 (PP1), particularly PP1γ, which mediates the dephosphorylation of Gwl Ser-883. Consistent with the mitotic activation of Gwl, its association with PP1 is disrupted in mitotic cells and egg extracts...
April 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28442576/determination-of-dendritic-spine-morphology-by-the-striatin-scaffold-protein-strn4-through-interaction-with-the-phosphatase-pp2a
#10
Lianfeng Lin, Louisa Hoi-Ying Lo, Quanwei Lyu, Kwok-On Lai
Dendritic spines are heterogeneous and exist with various morphologies. Altered spine morphology might underlie the cognitive deficits in neurodevelopmental disorders such as autism, but how different subtypes of dendritic spines are selectively maintained along development is still poorly understood. Spine maturation requires spontaneous activity of N-methyl-D-aspartate (NMDA) receptor and local dendritic protein synthesis. STRN4 (also called Zinedin) belongs to the striatin family of scaffold proteins, and some of the potential striatin-interacting proteins are encoded by autism risk genes...
April 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28442575/structure-and-energetics-of-pairwise-interactions-between-proteasome-subunits-rpn2-rpn13-and-ubiquitin-clarify-a-substrate-recruitment-mechanism
#11
Ryan T VanderLinden, Casey W Hemmis, Tingting Yao, Howard Robinson, Christopher P Hill
The 26S proteasome is a large cellular assembly that mediates the selective degradation of proteins in the nucleus and cytosol and is an established target for anti-cancer therapeutics. Protein substrates are typically targeted to the proteasome through modification with a polyubiquitin chain, which can be recognized by several proteasome-associated ubiquitin receptors. One of these receptors, RPN13/ADRM1, is recruited to the proteasome through direct interaction with the large scaffolding protein RPN2 within the 19S regulatory particle...
April 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28442574/the-r753q-polymorphism-in-toll-like-receptor-2-tlr2-attenuates-innate-immune-responses-to-mycobacteria-and-impairs-myd88-adapter-recruitment-to-tlr2
#12
Goutham Pattabiraman, Rahul Panchal, Andrei E Medvedev
Toll-like receptor (TLR) 2 plays a critical role in host defenses against mycobacterial infections. The Arg753Gln (R753Q) TLR2 polymorphism has been associated with increased incidence of tuberculosis and infections with non-tuberculous mycobacteria in human populations, but the mechanisms by which this polymorphism affects TLR2 signaling are unclear. In this study, we determined the impact of the R753Q TLR2 polymorphism on macrophage sensing of Mycobacterium smegmatis. Upon infection with M. smegmatis, macrophages from knock-in (KI) mice harboring R753Q TLR2 expressed lower levels of TNF-α, IL-1β, IL-6 and IL-10 compared to cells from wild-type (WT) mice but both R753Q TLR2 and WT mice exhibited comparable bacterial burdens...
April 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28442573/cell-cycle-dependent-degradation-of-the-methyltransferase-setd3-attenuates-cell-proliferation-and-liver-tumorigenesis
#13
Xiaoqing Cheng, Yuan Hao, Wenjie Shu, Mengjie Zhao, Chen Zhao, Yuan Wu, Xiaodan Peng, Pinfang Yao, Daibiao Xiao, Guoliang Qing, Zhengying Pan, Lei Yin, Desheng Hu, Hai-Ning Du
Histone modifications, including lysine methylation, are epigenetic marks that influence many biological pathways. Accordingly, many methyltransferases have critical roles in various biological processes, and their dysregulation is often associated with cancer. However, the biological functions and regulation of many methyltransferases are unclear. Here, we report that a human homolog of the methyltransferase SET domain containing 3 (SETD3) is cell cycle regulated: SETD3 protein levels peaked in S phase and were lowest in M phase...
April 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28442572/the-phospholipase-ipla2%C3%AE-is-a-major-mediator-releasing-oxidized-aliphatic-chains-from-cardiolipin-integrating-mitochondrial-bioenergetics-and-signaling
#14
Gao-Yuan Liu, Sung Ho Moon, Christopher M Jenkins, Maoyin Li, Harold F Sims, Shaoping Guan, Richard W Gross
Cardiolipin (CL) is a dimeric phospholipid with critical roles in mitochondrial bioenergetics and signaling. Recently, inhibition of the release of oxidized fatty acyl chains from CL by the calcium independent phospholipase A2γ (iPLA2γ) selective inhibitor (R)-BEL suggested that iPLA2γ is responsible for the hydrolysis of oxidized CL and subsequent signaling mediated by the released oxidized fatty acids. However, chemical inhibition by BEL is subject to off-target pharmacologic effects. Accordingly, to unambiguously determine the role of iPLA2γ in the hydrolysis of oxidized CL, we compared alterations in oxidized CLs and the release of oxidized aliphatic chains from CL in experiments with purified recombinant iPLA2γ, germline iPLA2γ(-/-) mice, cardiac myocyte-specific iPLA2γ transgenic mice, and wild-type mice...
April 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28442571/beta-2-adrenergic-receptor-activation-mobilizes-intracellular-calcium-via-a-non-canonical-camp-independent-signaling-pathway
#15
Monica Galaz-Montoya, Sara J Wright, Gustavo J Rodriguez, Olivier Lichtarge, Theodore G Wensel
Beta adrenergic receptors (βARs) are G protein-coupled receptors essential for physiological responses to the hormones/neurotransmitters epinephrine and norepinephrine which are found in the nervous system and throughout the body. They are the targets of numerous widely used drugs, especially in the case of the most extensively studied βAR, β2AR, whose ligands are used for asthma and cardiovascular disease. βARs signal through Gαs G proteins and via activation of adenylyl cyclase and cAMP-dependent protein kinase, but some alternative downstream pathways have also been proposed, which could be important for understanding normal physiological functioning of β2AR signaling and its disruption in disease...
April 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28442570/coordination-chemistry-controls-the-thiol-oxidase-activity-of-the-b12-trafficking-protein-cblc
#16
Zhu Li, Aranganathan Shanmuganathan, Markus Ruetz, Kazuhiro Yamada, Nicholas A Lesniak, Bernhard Kraeutler, Thomas C Brunold, Markos Koutmos, Ruma Banerjee
The cobalamin or B12 cofactor supports sulfur and one-carbon metabolism and the catabolism of odd-chain fatty acids, branched-chain amino acids and cholesterol. CblC is a B12 processing enzyme involved in an early cytoplasmic step in the cofactor trafficking pathway. It catalyzes the glutathione (GSH)-dependent dealkylation of alkylcobalamins and the reductive decyanation of cyanocobalamin. CblC from Caenorhabdiitis elegans (ceCblC) also exhibits a robust thiol oxidase activity converting reduced GSH to oxidized GSSG with concomitant scrubbing of ambient dissolved O2 The mechanism of thiol oxidation catalyzed by ceCblC is not known...
April 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28438838/allosteric-mechanism-of-action-of-the-therapeutic-anti-ige-antibody-omalizumab
#17
Anna M Davies, Elizabeth G Allan, Anthony H Keeble, Jean Delgado, Benjamin P Cossins, Alkistis N Mitropoulou, Marie O Y Pang, Tom Ceska, Andrew J Beavil, Graham Craggs, Marta Westwood, Alistair J Henry, James M McDonnell, Brian J Sutton
Immunoglobulin E and its interactions with receptors FcϵRI and CD23 play a central role in allergic disease. Omalizumab, a clinically-approved therapeutic antibody, inhibits the interaction between IgE and FcϵRI, preventing mast cell and basophil activation, and blocks IgE binding to CD23 on B cells and antigen-presenting cells. We solved the crystal structure of the complex between an omalizumab-derived Fab and IgE-Fc, with one Fab bound to each Cϵ3 domain. Free IgE-Fc adopts an acutely bent structure, but in the complex it is only partially bent, with large-scale conformational changes in the Cϵ3 domains that inhibit the interaction with FcϵRI...
April 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28438837/an-unpredicted-aggregation-critical-region-of-the-actin-polymerizing-protein-triobp-1-tara-determined-by-elucidation-of-its-domain-structure
#18
Nicholas J Bradshaw, Antony S K Yerabham, Rita Marreiros, Tao Zhang, Luitgard Nagel-Steger, Carsten Korth
Protein aggregation resulting from disruptions in proteostasis in the brains of patients with chronic mental illness is an emerging theme particularly in the study of schizophrenia. For example, proteins such as Disrupted in Schizophrenia 1 (DISC1) and dysbindin-1B are present in insoluble aggregates, detectable within brain homogenates from such patients. Using an epitope discovery and proteomics approach to compare post-mortem brain samples from schizophrenia patients and controls, we recently identified TRIO-Binding Protein 1 (TRIOBP-1, also known as Tara) as another aggregation-associated protein...
April 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28438836/a-wnt-notch-pax7-signaling-network-supports-tissue-integrity-in-tongue-development
#19
Xiao-Jing Zhu, Xueyan Yuan, Min Wang, Yukun Fang, Yudong Liu, Xiaoyun Zhang, Xueqin Yang, Yan Li, Jianying Li, Feixue Li, Zhong-Min Dai, Mengsheng Qiu, Ze Zhang, Zunyi Zhang
The tongue is one of the major structures involved in human food intake and speech. Tongue malformations such as aglossia, microglossia, and ankyloglossia are congenital birth defects, greatly affecting individuals' quality of life. However, the molecular basis of the tissue-tissue interactions that ensure tissue morphogenesis to form a functional tongue remains largely unknown. Here we show that ShhCre-mediated epithelial deletion of Wntless (Wls), the key regulator for intracellular Wnt trafficking, leads to lingual hypoplasia in mice...
April 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28438835/il-1%C3%AE-transcriptionally-activates-hepcidin-by-inducing-c-ebp%C3%AE-expression-in-hepatocytes
#20
Yohei Kanamori, Masaru Murakami, Makoto Sugiyama, Osamu Hashimoto, Tohru Matsui, Masayuki Funaba
Hepcidin is a liver-derived hormone that negatively regulates serum iron levels and is mainly regulated at the transcriptional level. Previous studies have clarified that in addition to hepatic iron levels, inflammation also efficiently increases hepatic hepcidin expression. The principle regions responsible for efficient hepcidin transcription are bone morphogenetic protein-responsive elements (BMP-REs) 1 and 2 as well as the signal transducer and activator of transcription 3-binding site (STAT-BS). Here, we show that the proinflammatory cytokine interleukin-1β (IL-1β) efficiently increases hepcidin expression in human HepG2 liver-derived cells and primary mouse hepatocytes...
April 24, 2017: Journal of Biological Chemistry
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