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https://www.readbyqxmd.com/read/29187538/the-absence-of-dhhc3-affects-primary-and-latent-hsv-1-infection
#1
Shaohui Wang, Kevin R Mott, Marianne Cilluffo, Casey L Kilpatrick, Shoko Murakami, Alexander V Ljubimov, Konstantin G Kousoulas, Sita Awasthi, Bernhard Luscher, Homayon Ghiasi
UL20, an essential HSV-1 protein, is involved in cytoplasmic envelopment of virions and virus egress. We reported recently that UL20 can bind to a host protein encoded by the zinc finger DHHC-type containing 3 (ZDHHC3) gene (also known as Golgi-specific DHHC zinc finger protein {GODZ}). Here, we show for the first time that HSV-1 replication is compromised in murine embryonic fibroblasts (MEFs) isolated from GODZ-/- mice. The absence of GODZ resulted in reduced palmitoylation of UL20 and altered localization, expression of UL20 and gK; the expression of gB and gC; and the localization and expression of tegument and capsid proteins within HSV-1-infected MEFs...
November 29, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29079573/the-palmitoyltransferase-zdhhc20-enhances-interferon-induced-transmembrane-protein-3-ifitm3-palmitoylation-and-antiviral-activity
#2
Temet M McMichael, Lizhi Zhang, Mahesh Chemudupati, Jocelyn C Hach, Adam D Kenney, Howard C Hang, Jacob S Yount
Interferon-induced transmembrane protein 3 (IFITM3) is a cellular endosome- and lysosome-localized protein that restricts numerous virus infections. IFITM3 is activated by palmitoylation, a lipid posttranslational modification. Palmitoylation of proteins is primarily mediated by zinc finger DHHC domain-containing palmitoyltransferases (ZDHHCs), but which members of this enzyme family can modify IFITM3 is not known. Here, we screened a library of human cell lines individually lacking ZDHHCs 1-24, and found that IFITM3 palmitoylation and its inhibition of influenza virus infection remained strong in the absence of any single ZDHHC, suggesting functional redundancy of these enzymes in the IFITM3-mediated antiviral response...
October 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29055014/protein-acyltransferase-dhhc3-regulates-breast-tumor-growth-oxidative-stress-and-senescence
#3
Martin E Hemler, Chandan Sharma, Hong-Xing Wang, Qinglin Li, Konstantin Knoblich, Emily S Reisenbichler, Andrea L Richardson
DHHC-type protein acyltransferases may regulate the localization, stability and/or activity of their substrates. In this study, we show that the protein palmitoyltransferase DHHC3 is upregulated in malignant and metastatic human breast cancer. Elevated expression of DHHC3 correlated with diminished patient survival in breast cancer and six other human cancer types. ZDHHC3 ablation in human MDA-MB-231 mammary tumor cell xenografts reduced the sizes of both the primary tumor and metastatic lung colonies. Gene array data and fluorescence dye assays documented increased oxidative stress and senescence in ZDHHC3-ablated cells...
October 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/29046345/endoplasmic-reticulum-transmembrane-proteins-zdhhc1-and-sting-both-act-as-direct-adaptors-for-irf3-activation-in-teleost
#4
Xiaowen Xu, Meifeng Li, Zhen Wu, Haizhou Wang, Liqiang Wang, Keyi Huang, Xiancheng Liu, Qunhao Hou, Gang Lin, Chengyu Hu
IFN regulatory factor (IRF)3 is a central regulator for IFN-β expression in different types of pathogenic infections. Mammals have various pathogenic sensors that are involved in monitoring pathogen intrusions. These sensors can trigger IRF3-mediated antiviral responses through different pathways. Endoplasmic reticulum-associated proteins stimulator of IFN gene (STING) and zinc finger DHHC-type containing 1 (ZDHHC1) are critical mediators of IRF3 activation in response to viral DNA infections. In this study, grass carp STING and ZDHHC1 were found to have some similar molecular features and subcellular localization, and both were upregulated upon stimulation with polyinosinic:polycytidylic acid, B-DNA, or Z-DNA...
October 18, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29038583/zdhhc13-dependent-drp1-s-palmitoylation-impacts-brain-bioenergetics-anxiety-coordination-and-motor-skills
#5
Eleonora Napoli, Gyu Song, Siming Liu, Alexsandra Espejo, Carlos J Perez, Fernando Benavides, Cecilia Giulivi
Protein S-palmitoylation is a reversible post-translational modification mediated by palmitoyl acyltransferase enzymes, a group of Zn(2+)-finger DHHC-domain-containing proteins (ZDHHC). Here, for the first time, we show that Zdhhc13 plays a key role in anxiety-related behaviors and motor function, as well as brain bioenergetics, in a mouse model (luc) carrying a spontaneous Zdhhc13 recessive mutation. At 3 m of age, mutant mice displayed increased sensorimotor gating, anxiety, hypoactivity, and decreased motor coordination, compared to littermate controls...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28962849/the-expression-of-select-genes-necessary-for-membrane-associated-estrogen-receptor-signaling-differ-by-sex-in-adult-rat-hippocampus
#6
John Meitzen, Kyla A Britson, Krista Tuomela, Paul G Mermelstein
17β-estradiol can rapidly modulate neuron function via membrane estrogen receptors (ERs) in a sex-specific manner. For example, female rat hippocampal neurons express palmitoylated versions of ERα and ERβ that associate with the plasma membrane. These membrane-associated ERs are organized by caveolin proteins into functional signaling microdomains with metabotropic glutamate receptors (mGluRs). ER/mGluR signaling mediates several sex-specific estradiol actions on hippocampal neuron function. An important unanswered question regards the mechanism by which sex-specific membrane-associated ER signaling is generated, especially since it has been previously demonstrated that mGluR action is not sex-specific...
September 28, 2017: Steroids
https://www.readbyqxmd.com/read/28826475/identification-and-dynamics-of-the-human-zdhhc16-zdhhc6-palmitoylation-cascade
#7
Laurence Abrami, Tiziano Dallavilla, Patrick A Sandoz, Mustafa Demir, Béatrice Kunz, Georgios Savoglidis, Vassily Hatzimanikatis, F Gisou van der Goot
S-Palmitoylation is the only reversible post-translational lipid modification. Knowledge about the DHHC palmitoyltransferase family is still limited. Here we show that human ZDHHC6, which modifies key proteins of the endoplasmic reticulum, is controlled by an upstream palmitoyltransferase, ZDHHC16, revealing the first palmitoylation cascade. The combination of site specific mutagenesis of the three ZDHHC6 palmitoylation sites, experimental determination of kinetic parameters and data-driven mathematical modelling allowed us to obtain detailed information on the eight differentially palmitoylated ZDHHC6 species...
August 15, 2017: ELife
https://www.readbyqxmd.com/read/28757145/structural-basis-for-substrate-recognition-by-the-ankyrin-repeat-domain-of-human-dhhc17-palmitoyltransferase
#8
Raffaello Verardi, Jin-Sik Kim, Rodolfo Ghirlando, Anirban Banerjee
DHHC enzymes catalyze palmitoylation, a major post-translational modification that regulates a number of key cellular processes. There are up to 24 DHHCs in mammals and hundreds of substrate proteins that get palmitoylated. However, how DHHC enzymes engage with their substrates is still poorly understood. There is currently no structural information about the interaction between any DHHC enzyme and protein substrates. In this study we have investigated the structural and thermodynamic bases of interaction between the ankyrin repeat domain of human DHHC17 (ANK17) and Snap25b...
September 5, 2017: Structure
https://www.readbyqxmd.com/read/28734079/post-translational-palmitoylation-controls-the-voltage-gating-and-lipid-raft-association-of-the-calhm1-channel
#9
Akiyuki Taruno, Hongxin Sun, Koichi Nakajo, Tatsuro Murakami, Yasuyoshi Ohsaki, Mizuho A Kido, Fumihito Ono, Yoshinori Marunaka
KEY POINTS: Calcium homeostasis modulator 1 (CALHM1), a new voltage-gated ATP- and Ca(2+) -permeable channel, plays important physiological roles in taste perception and memory formation. Regulatory mechanisms of CALHM1 remain unexplored, although the biophysical disparity between CALHM1 gating in vivo and in vitro suggests that there are undiscovered regulatory mechanisms. Here we report that CALHM1 gating and association with lipid microdomains are post-translationally regulated through the process of protein S-palmitoylation, a reversible attachment of palmitate to cysteine residues...
September 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28724772/binding-of-herpes-simplex-virus-1-ul20-to-godz-dhhc3-affects-its-palmitoylation-and-is-essential-for-infectivity-and-proper-targeting-and-localization-of-ul20-and-glycoprotein-k
#10
Shaohui Wang, Kevin R Mott, Kolja Wawrowsky, Konstantin G Kousoulas, Bernhard Luscher, Homayon Ghiasi
Herpes simplex virus 1 (HSV-1) UL20 plays a crucial role in the envelopment of the cytoplasmic virion and its egress. It is a nonglycosylated envelope protein that is regulated as a γ1 gene. Two-hybrid and pulldown assays demonstrated that UL20, but no other HSV-1 gene-encoded proteins, binds specifically to GODZ (also known as DHHC3), a cellular Golgi apparatus-specific Asp-His-His-Cys (DHHC) zinc finger protein. A catalytically inactive dominant-negative GODZ construct significantly reduced HSV-1 replication in vitro and affected the localization of UL20 and glycoprotein K (gK) and their interactions but not glycoprotein C (gC)...
October 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28630137/structure-and-function-of-dhhc-protein-s-acyltransferases
#11
REVIEW
Colin D Gottlieb, Maurine E Linder
It has been estimated that 10% of the human genome encodes proteins that are fatty acylated at cysteine residues. The vast majority of these proteins are modified by members of the DHHC protein family, which carry out their enzymatic function on the cytoplasmic face of cell membranes. The biomedical importance of DHHC proteins is underscored by their association with human disease; unique and essential roles for DHHC proteins have been uncovered using DHHC-deficient mouse models. Accordingly, there is great interest in elucidating the molecular mechanisms that underlie DHHC protein function...
August 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28167757/molecular-basis-of-fatty-acid-selectivity-in-the-zdhhc-family-of-s-acyltransferases-revealed-by-click-chemistry
#12
Jennifer Greaves, Kevin R Munro, Stuart C Davidson, Matthieu Riviere, Justyna Wojno, Terry K Smith, Nicholas C O Tomkinson, Luke H Chamberlain
S-acylation is a major posttranslational modification, catalyzed by the zinc finger DHHC domain containing (zDHHC) enzyme family. S-acylated proteins can be modified by different fatty acids; however, very little is known about how zDHHC enzymes contribute to acyl chain heterogeneity. Here, we used fatty acid-azide/alkyne labeling of mammalian cells, showing their transformation into acyl-CoAs and subsequent click chemistry-based detection, to demonstrate that zDHHC enzymes have marked differences in their fatty acid selectivity...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28154191/specific-palmitoyltransferases-associate-with-and-activate-the-epithelial-sodium-channel
#13
Anindit Mukherjee, Zhijian Wang, Carol L Kinlough, Paul A Poland, Allison L Marciszyn, Nicolas Montalbetti, Marcelo D Carattino, Michael B Butterworth, Thomas R Kleyman, Rebecca P Hughey
The epithelial sodium channel (ENaC) has an important role in regulating extracellular fluid volume and blood pressure, as well as airway surface liquid volume and mucociliary clearance. ENaC is a trimer of three homologous subunits (α, β, and γ). We previously reported that cytoplasmic residues on the β (βCys-43 and βCys-557) and γ (γCys-33 and γCys-41) subunits are palmitoylated. Mutation of Cys that blocked ENaC palmitoylation also reduced channel open probability. Furthermore, γ subunit palmitoylation had a dominant role over β subunit palmitoylation in regulating ENaC...
March 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28057756/dhhc7-palmitoylates-glucose-transporter-4-glut4-and-regulates-glut4-membrane-translocation
#14
Keyong Du, Shoko Murakami, Yingmin Sun, Casey L Kilpatrick, Bernhard Luscher
Insulin-dependent translocation of glucose transporter 4 (Glut4) to the plasma membrane plays a key role in the dynamic regulation of glucose homeostasis. We recently showed that this process is critically dependent on palmitoylation of Glut4 at Cys-223. To gain further insights into the regulation of Glut4 palmitoylation, we set out to identify the palmitoyl acyltransferase (PAT) involved. Here we report that among 23 mammalian DHHC proteins, DHHC7 is the major Glut4 PAT, based on evidence that ectopic expression of DHHC7 increased Glut4 palmitoylation, whereas DHHC7 knockdown in 3T3-L1 adipocytes and DHHC7 KO in adipose tissue and muscle decreased Glut4 palmitoylation...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28031421/the-palmitoyltransferase-approximated-promotes-growth-via-the-hippo-pathway-by-palmitoylation-of-fat
#15
Hitoshi Matakatsu, Seth S Blair, Richard G Fehon
The large protocadherin Fat functions to promote Hippo pathway activity in restricting tissue growth. Loss of Fat leads to accumulation of the atypical myosin Dachs at the apical junctional region, which in turn promotes growth by inhibiting Warts. We previously identified Approximated (App), a DHHC domain palmitoyltransferase, as a negative regulator of Fat signaling in growth control. We show here that App promotes growth by palmitoylating the intracellular domain of Fat, and that palmitoylation negatively regulates Fat function...
January 2, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/27964781/plant-architecture-and-grain-yield-are-regulated-by-the-novel-dhhc-type-zinc-finger-protein-genes-in-rice-oryza-sativa-l
#16
Bo Zhou, Jian Zhong Lin, Dan Peng, Yuan Zhu Yang, Ming Guo, Dong Ying Tang, Xiaofeng Tan, Xuan Ming Liu
In many plants, architecture and grain yield are affected by both the environment and genetics. In rice, the tiller is a vital factor impacting plant architecture and regulated by many genes. In this study, we cloned a novel DHHC-type zinc finger protein gene Os02g0819100 and its alternative splice variant OsDHHC1 from the cDNA of rice (Oryza sativa L.), which regulate plant architecture by altering the tiller in rice. The tillers increased by about 40% when this type of DHHC-type zinc finger protein gene was over-expressed in Zhong Hua 11 (ZH11) rice plants...
January 2017: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/27875292/dissociation-of-golgi-associated-dhhc-type-zinc-finger-protein-godz-and-sertoli-cell-gene-with-a-zinc-finger-domain-%C3%AE-serz-%C3%AE-mediated-palmitoylation-by-loss-of-function-analyses-in-knock-out-mice
#17
Casey L Kilpatrick, Shoko Murakami, Mengyang Feng, Xia Wu, Rachnanjali Lal, Gong Chen, Keyong Du, Bernhard Luscher
The γ2 subunit of GABA type A receptors (GABAARs) is thought to be subject to palmitoylation by both Golgi-associated DHHC-type zinc finger protein (GODZ; also known as DHHC3) and its paralog Sertoli cell gene with a zinc finger domain-β (SERZ-β; DHHC7) based on overexpression of enzymes and substrates in heterologous cells. Here we have further investigated the substrate specificity of these enzymes by characterization of GODZ and SERZ-β knock-out (KO) mice as well as double KO (DKO) neurons. Palmitoylation of γ2 and a second substrate, growth-associated protein of 43 kDa, that is independently implicated in trafficking of GABAARs was significantly reduced in brain of GODZ KO versus wild-type (WT) mice but unaltered in SERZ-β KO mice...
December 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27558878/chemical-probes-to-directly-profile-palmitoleoylation-of-proteins
#18
Baohui Zheng, Gopala K Jarugumilli, Baoen Chen, Xu Wu
Palmitoleoylation is a unique fatty acylation of proteins in which a monounsaturated fatty acid, palmitoleic acid (C16:1), is covalently attached to a protein. Wnt proteins are known to be palmitoleoylated by cis-Δ9 palmitoleate at conserved serine residues. O-palmitoleoylation plays a critical role in regulating Wnt secretion, binding to the receptors, and in the dynamics of Wnt signaling. Therefore, protein palmitoleoylation is important in tissue homeostasis and tumorigenesis. Chemical probes based on saturated fatty acids, such as ω-alkynyl palmitic acid (Alk-14 or Alk-C16 ), have been used to study Wnt palmitoleoylation...
November 3, 2016: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/27426946/potentiation-of-surface-stability-of-ampa-receptors-by-sulfhydryl-compounds-a-redox-independent-effect-by-disrupting-palmitoylation
#19
Jun Han, Hai Zhang, Sheng Wang, Jun Zhou, Yi Luo, Li-Hong Long, Zhuang-Li Hu, Fang Wang, Jian-Guo Chen, Peng-Fei Wu
Sulfhydryl compounds such as dithiothreitol (DTT) and β-mercaptoethanol (β-ME) are widely used as redox agents. Previous studies in our group and other laboratory have reported the effect of sulfhydryl compounds on the function of glutamate receptor, including plasticity. Most of these findings have focused on the N-methyl-D-aspartic acid receptor, in contrast, very little is known about the effect of sulfhydryl compounds on α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR). Here, we observed that DTT (100 μM), β-ME (200 μM) and L-cysteine (200 μM) significantly elevated the surface expression of AMPARs via reducing their palmitoylation in rat hippocampal slices in vitro...
November 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27307232/identification-of-psd-95-depalmitoylating-enzymes
#20
Norihiko Yokoi, Yuko Fukata, Atsushi Sekiya, Tatsuro Murakami, Kenta Kobayashi, Masaki Fukata
UNLABELLED: Postsynaptic density (PSD)-95, the most abundant postsynaptic scaffolding protein, plays a pivotal role in synapse development and function. Continuous palmitoylation cycles on PSD-95 are essential for its synaptic clustering and regulation of AMPA receptor function. However, molecular mechanisms for palmitate cycling on PSD-95 remain incompletely understood, as PSD-95 depalmitoylating enzymes remain unknown. Here, we isolated 38 mouse or rat serine hydrolases and found that a subset specifically depalmitoylated PSD-95 in heterologous cells...
June 15, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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