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Ubiquitination

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https://www.readbyqxmd.com/read/28226265/alterations-of-ubiquitin-related-proteins-in-the-pathology-and-development-of-schizophrenia-evidence-from-human-and-animal-studies
#1
Jessica L Andrews, Frederic J Goodfellow, Natalie Matosin, Mollie K Snelling, Kelly A Newell, Xu-Feng Huang, Francesca Fernandez-Enright
Gene expression analyses in post-mortem schizophrenia brains suggest that a number of ubiquitin proteasome system (UPS) genes are associated with schizophrenia; however the status of UPS proteins in the schizophrenia brain is largely unknown. Ubiquitin related proteins are inherently involved in memory, neuronal survival and morphology, which are processes implicated in neurodevelopmental disorders such as schizophrenia. We examined levels of five UPS proteins (Protein Inhibitor of Activated STAT2 [PIAS2], F-Box and Leucine rich repeat protein 21 [FBXL21], Mouse Double Minute 2 homolog [MDM2], Ubiquitin Carboxyl-Terminal Hydrolase-L1 [UCHL1] and Ubiquitin Conjugating Enzyme E2D1 [UBE2D1]) involved in these neuronal processes, within the dorsolateral prefrontal cortex of post-mortem schizophrenia subjects and matched controls (n = 30/group), in addition to across neurodevelopmental time-points (juvenile, adolescent and adult stages of life), utilizing a well-established neurodevelopmental phencyclidine (PCP) animal model of schizophrenia...
January 18, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28225045/membrane-targeting-of-tirap-is-negatively-regulated-by-phosphorylation-in-its-phosphoinositide-binding-motif
#2
Xiaolin Zhao, Wen Xiong, Shuyan Xiao, Tuo-Xian Tang, Jeffrey F Ellena, Geoffrey S Armstrong, Carla V Finkielstein, Daniel G S Capelluto
Pathogen-activated Toll-like receptors (TLRs), such as TLR2 and TLR4, dimerize and move laterally across the plasma membrane to phosphatidylinositol (4,5)-bisphosphate-enriched domains. At these sites, TLRs interact with the TIR domain-containing adaptor protein (TIRAP), triggering a signaling cascade that leads to innate immune responses. Membrane recruitment of TIRAP is mediated by its phosphoinositide (PI)-binding motif (PBM). We show that TIRAP PBM transitions from a disordered to a helical conformation in the presence of either zwitterionic micelles or monodispersed PIs...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28224479/modulation-of-arts-and-xiap-by-parkin-is-associated-with-carnosic-acid-protects-sh-sy5y-cells-against-6-hydroxydopamine-induced-apoptosis
#3
Ru-Huei Fu, Li-Chun Huang, Chia-Yuan Lin, Chia-Wen Tsai
The mediation of apoptosis-related protein in the TGF-β signaling pathway (ARTS) and X-liked inhibitor of apoptosis protein (XIAP) by parkin plays a critical role in preventing Parkinson's disease. We studied whether carnosic acid (CA) could prevent 6-hydroxydopamine (6-OHDA)-induced apoptosis by modulating ARTS and XIAP through parkin in SH-SY5Y cells. In cells treated with 6-OHDA, the protein expression of ARTS is increased and XIAP is decreased. Pretreatment of cells with CA reversed these effects. Moreover, CA attenuated the activation of caspase 9 and caspase 7 by 6-OHDA...
February 21, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28224114/ha-triggers-the-switch-from-mek1-sumoylation-to-phosphorylation-of-the-erk-pathway-in-influenza-a-virus-infected-cells-and-facilitates-its-infection
#4
Chengmin Wang, Huimin Liu, Jing Luo, Lin Chen, Meng Li, Wen Su, Na Zhao, Shelan Liu, Li Xie, Yaxiong Jia, Hua Ding, Xiufeng Wan, Hongxuan He
Several post-translational modifications in host cells are hijacked by pathogens to facilitate their propagation. A number of components of the influenza virus have been reported to be modified by small ubiquitin-like modifier (SUMO) proteins during infection. We hypothesized that the MAPK/ERK pathway could be modified by SUMO1 because the SUMOylation of MEK1 was quickly eliminated after influenza A virus infection. We identified host cell MEK1 as a target of SUMO1 through LC/MS/MS, and enhanced MEK1 SUMOylation inhibited the infection of the virus, while inhibition of host cell MEK1 SUMOylation facilitated virus propagation...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28223829/cul4a-promotes-proliferation-and-metastasis-of-colorectal-cancer-cells-by-regulating-h3k4-trimethylation-in-epithelial-mesenchymal-transition
#5
Xuemei Sui, Hong Zhou, Lei Zhu, Deqiang Wang, Sumei Fan, Wei Zhao
Increasing evidence suggests that CUL4A, a ubiquitin ligase, is involved in the promotion of cancer malignancy and correlated with worse clinical prognosis in several kinds of human cancers. Although its effect and mechanism on the progression of colorectal cancer (CRC) remain unknown. Our clinical data show that CUL4A protein is overexpressed, positively associated with lymph nodes status, differentiation degree, tumor size, and poor prognosis in 80 CRC patients. CUL4A overexpression promotes cell proliferation and colony formation of CRC cells...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28223825/usp21-promotes-cell-proliferation-and-metastasis-through-suppressing-ezh2-ubiquitination-in-bladder-carcinoma
#6
Yong Chen, Bo Zhou, Daihui Chen
Bladder cancer (BC) is the second most common malignant tumor of the urinary tract in the world. In this study, we found that ubiquitin-specific protease (USP21) was upregulated in BC and the ectopic expression of USP21 was closely associated with tumor size and metastasis. Moreover, patients with higher levels of USP21 had poorer survival rate. Multiple function analysis such as CCK-8, colony formation, wound healing, and transwell analysis indicated that USP21 regulated cell proliferation and metastasis in bladder carcinoma cell lines...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28223714/comparative-physiological-and-transcriptomic-analyses-provide-integrated-insight-into-osmotic-cold-and-salt-stress-tolerance-mechanisms-in-banana
#7
Wei Hu, Zehong Ding, Weiwei Tie, Yan Yan, Yang Liu, Chunlai Wu, Juhua Liu, Jiashui Wang, Ming Peng, Biyu Xu, Zhiqiang Jin
The growth, development, and production of banana plants are constrained by multiple abiotic stressors. However, it remains elusive for the tolerance mechanisms of banana responding to multiple abiotic stresses. In this study, we found that Fen Jiao (FJ) was more tolerant to osmotic, cold, and salt stresses than BaXi Jiao (BX) by phenotypic and physiological analyses. Comparative transcriptomic analyses highlighted stress tolerance genes that either specifically regulated in FJ or changed more than twofold in FJ relative to BX after treatments...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28223538/tissue-transglutaminase-induces-epithelial-mesenchymal-transition-and-the-acquisition-of-stem-cell-like-characteristics-in-colorectal-cancer-cells
#8
Oluseyi Ayinde, Zhuo Wang, Martin Griffin
Human colon cancer cell lines (CRCs) RKO, SW480 and SW620 were investigated for TG2 involvement in tumour advancement and aggression. TG2 expression correlated with tumour advancement and expression of markers of epithelial-mesenchymal transition (EMT). The metastatic cell line SW620 showed high TG2 expression compared to the primary tumour cell lines SW480 and RKO and could form tumour spheroids under non- adherent conditions. TG2 manipulation in the CRCs by shRNA or TG2 transduction confirmed the relationship between TG2 and EMT...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28223512/glucosylceramide-synthase-inhibition-alleviates-aberrations-in-synucleinopathy-models
#9
S Pablo Sardi, Catherine Viel, Jennifer Clarke, Christopher M Treleaven, Amy M Richards, Hyejung Park, Maureen A Olszewski, James C Dodge, John Marshall, Elina Makino, Bing Wang, Richard L Sidman, Seng H Cheng, Lamya S Shihabuddin
Mutations in the glucocerebrosidase gene (GBA) confer a heightened risk of developing Parkinson's disease (PD) and other synucleinopathies, resulting in a lower age of onset and exacerbating disease progression. However, the precise mechanisms by which mutations in GBA increase PD risk and accelerate its progression remain unclear. Here, we investigated the merits of glucosylceramide synthase (GCS) inhibition as a potential treatment for synucleinopathies. Two murine models of synucleinopathy (a Gaucher-related synucleinopathy model, Gba(D409V/D409V) and a A53T-α-synuclein overexpressing model harboring wild-type alleles of GBA, A53T-SNCA mouse model) were exposed to a brain-penetrant GCS inhibitor, GZ667161...
February 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28223451/mycobacterium-tuberculosis-proteasome-accessory-factor-a-pafa-can-transfer-prokaryotic-ubiquitin-like-protein-pup-between-substrates
#10
Susan Zhang, Kristin E Burns-Huang, Guido V Janssen, Huilin Li, Huib Ovaa, Lizbeth Hedstrom, K Heran Darwin
The protein degradation machinery of Mycobacterium tuberculosis includes a proteasome and a ubiquitin-like protein (Pup). Proteasome accessory factor A (PafA) attaches Pup to proteins to target them for degradation by the proteasome. Free Pup is unstable and never observed in extracts of M. tuberculosis, an observation that led us to hypothesize that PafA may need alternative sources of Pup. Here, we show that PafA can move Pup from one proteasome substrate, inositol 1-phosphate synthetase (Ino1), to two different proteins, malonyl coenzyme A (CoA)-acyl carrier protein transacylase (FabD) and lonely guy (Log)...
February 21, 2017: MBio
https://www.readbyqxmd.com/read/28223439/sumoylation-of-turnip-mosaic-virus-rna-polymerase-promotes-viral-infection-by-counteracting-the-host-npr1-mediated-immune-response
#11
Xiaofei Cheng, Ruyi Xiong, Yinzi Li, Fangfang Li, Xueping Zhou, Aiming Wang
Sumoylation is a transient, reversible dynamic posttranslational modification that regulates diverse cellular processes including plant-pathogen interactions. Sumoylation of NPR1, a master regulator of basal and systemic acquired resistance to a broad spectrum of plant pathogens, activates the defense response. Here, we report that NIb, the only RNA-dependent RNA polymerase of Turnip mosaic virus (TuMV) that targets the nucleus upon translation, interacts exclusively with and is sumoylated by SUMO3 (SMALL UBIQUITIN-LIKE MODIFIER3), but not the three other Arabidopsis thaliana SUMO paralogs...
February 21, 2017: Plant Cell
https://www.readbyqxmd.com/read/28223335/cooperation-of-musashi-2-numb-mdm2-and-p53-in-drug-resistance-and-malignant-biology-of-pancreatic-cancer
#12
Weiwei Sheng, Ming Dong, Chuanping Chen, Zixin Wang, Yunwei Li, Kewei Wang, Yuji Li, Jianping Zhou
Our earlier work showed that Musashi (MSI)-2 promoted the development of pancreatic cancer (PC) by down-regulating Numb, which prevented murine double-minute (MDM)-2-mediated p53 ubiquitin degradation. Thus, we investigate the relationship among MSI2, Numb, MDM2, and p53 in PC in vitro and invivo, an association that has not been reported to our knowledge. MSI2 had no relationship with mutant p53 (mtp53) and wild-type p53 (wtp53) in normal PC cells. However, in response to gemcitabine or cisplatin treatment, MSI2 silencing simultaneously down-regulated MDM2 and up-regulated Numb and wtp53 protein levels...
February 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28223321/a-non-canonical-function-of-ezh2-preserves-immune-homeostasis
#13
Ajithkumar Vasanthakumar, Dakang Xu, Aaron Tl Lun, Andrew J Kueh, Klaas Pjm van Gisbergen, Nadia Iannarella, Xiaofang Li, Liang Yu, Die Wang, Bryan Rg Williams, Stanley Cw Lee, Ian J Majewski, Dale I Godfrey, Gordon K Smyth, Warren S Alexander, Marco J Herold, Axel Kallies, Stephen L Nutt, Rhys S Allan
Enhancer of zeste 2 (Ezh2) mainly methylates lysine 27 of histone-H3 (H3K27me3) as part of the polycomb repressive complex 2 (PRC2) together with Suz12 and Eed. However, Ezh2 can also modify non-histone substrates, although it is unclear whether this mechanism has a role during development. Here, we present evidence for a chromatin-independent role of Ezh2 during T-cell development and immune homeostasis. T-cell-specific depletion of Ezh2 induces a pronounced expansion of natural killer T (NKT) cells, although Ezh2-deficient T cells maintain normal levels of H3K27me3...
February 21, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28223312/natural-variation-and-dosage-of-the-hei10-meiotic-e3-ligase-control-arabidopsis-crossover-recombination
#14
Piotr A Ziolkowski, Charles J Underwood, Christophe Lambing, Marina Martinez-Garcia, Emma J Lawrence, Liliana Ziolkowska, Catherine Griffin, Kyuha Choi, F Chris H Franklin, Robert A Martienssen, Ian R Henderson
During meiosis, homologous chromosomes undergo crossover recombination, which creates genetic diversity and balances homolog segregation. Despite these critical functions, crossover frequency varies extensively within and between species. Although natural crossover recombination modifier loci have been detected in plants, causal genes have remained elusive. Using natural Arabidopsis thaliana accessions, we identified two major recombination quantitative trait loci (rQTLs) that explain 56.9% of crossover variation in Col×Ler F2 populations...
February 21, 2017: Genes & Development
https://www.readbyqxmd.com/read/28223226/targeted-protein-degradation-by-protacs
#15
REVIEW
Taavi K Neklesa, James D Winkler, Craig M Crews
Targeted protein degradation using the PROTAC technology is emerging as a novel therapeutic method to address diseases driven by the aberrant expression of a disease-causing protein. PROTAC molecules are bifunctional small molecules that simultaneously bind a target protein and an E3-ubiquitin ligase, thus causing ubiquitination and degradation of the target protein by the proteasome. Like small molecules, PROTAC molecules possess good tissue distribution and the ability to target intracellular proteins. Herein, we highlight the advantages of protein degradation using PROTACs, and provide specific examples where degradation offers therapeutic benefit over classical enzyme inhibition...
February 13, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28222786/post-translational-modification-of-parkin
#16
REVIEW
Joy Chakraborty, Valentina Basso, Elena Ziviani
: Mutations in the gene encoding for the E3 ubiquitin ligase Parkin are associated to a rare form of familiar autosomal recessive Parkinsonism. Despite decades of research on the Parkin protein, whose structure has been recently solved, little is known about the specific signalling pathways that lead to Parkin activation. Parkin activity spans from mitochondria quality control to tumor suppression and stress protection; it is thus tempting to hypothesize that the broad impact of Parkin on cellular physiology might be the result of different post translational modifications that can be controlled by balanced opposing events...
February 21, 2017: Biology Direct
https://www.readbyqxmd.com/read/28222440/sumo-1-gene-silencing-inhibits-proliferation-and-promotes-apoptosis-of-human-gastric-cancer-sgc-7901-cells
#17
Lifang Jin, Kexin Shen, Tong Chen, Wei Yu, Huaiyu Zhang
BACKGROUND: It has been reported that blocking small ubiquitin-like modifier (SUMO) conjugation by silencing SUMO gene remarkably decreased tumor growth in vivo. However, few studies have examined the relationship between SUMO gene silencing and gastric cancer (GC). The study aims to explore the effects of SUMO-1 gene silencing on GC cell proliferation and apoptosis. METHODS: GC cells were cultured and divided into 5 groups: the blank group (without any transfection or treatment), the empty vector group (transfected with empty vector), the shRNA-SUMO-1-1 group (transfected with shRNA-SUMO-1-1 plasmid), the shRNA-SUMO-1-2 group (transfected with shRNA-SUMO-1-2 plasmid), and the shRNA-SUMO-1-3 group (transfected with shRNA-SUMO-1-3 plasmid)...
February 21, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28221366/pathway-wide-association-study-identifies-five-shared-pathways-associated-with-schizophrenia-in-three-ancestral-distinct-populations
#18
C Liu, C A Bousman, C Pantelis, E Skafidas, D Zhang, W Yue, I P Everall
Genome-wide association studies have confirmed the polygenic nature of schizophrenia and suggest that there are hundreds or thousands of alleles associated with increased liability for the disorder. However, the generalizability of any one allelic marker of liability is remarkably low and has bred the notion that schizophrenia may be better conceptualized as a pathway(s) disorder. Here, we empirically tested this notion by conducting a pathway-wide association study (PWAS) encompassing 255 experimentally validated Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways among 5033 individuals diagnosed with schizophrenia and 5332 unrelated healthy controls across three distinct ethnic populations; European-American (EA), African-American (AA) and Han Chinese (CH)...
February 21, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28220688/the-dnaj-protein-osdja6-negatively-regulates-rice-innate-immunity-to-the-blast-fungus-magnaporthe-oryzae
#19
Xionghui Zhong, Jiuxia Yang, Yanlong Shi, Xuli Wang, Guo-Liang Wang
Rice blast, caused by Magnaporthe oryzae (synonym: Pyricularia oryzae), severely reduces rice production and grain quality. The molecular mechanism of rice resistance to M. oryzae is not fully understood. In the present study, we identified a chaperone DnaJ protein, OsDjA6, that is involved in basal resistance to M. oryzae in rice. The OsDjA6 protein is distributed in the entire rice cell. The expression of OsDjA6 is significantly induced in rice after infection with a compatible isolate. Silencing of OsDjA6 in transgenic rice enhances resistance to M...
February 21, 2017: Molecular Plant Pathology
https://www.readbyqxmd.com/read/28220418/in-vitro-ubiquitination-activity-assays-in-plant-immune-responses
#20
Giulia Furlan, Marco Trujillo
Ubiquitination is a central posttranslational modification that impinges on the fate of proteins. While attachment of K48-linked chains onto soluble proteins marks them for proteolysis via the 26S proteasome, mono-ubiquitination or K63-linked chains result in the endocytosis and sorting through the endomembrane system of integral membrane proteins, such as pattern recognition receptors. In vitro ubiquitination assays allow the biochemical analysis of all individual components of the ubiquitination machinery and its potential substrates...
2017: Methods in Molecular Biology
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