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https://www.readbyqxmd.com/read/27903803/the-human-cytomegalovirus-ie1-protein-antagonizes-pml-nuclear-body-mediated-intrinsic-immunity-via-the-inhibition-of-pml-de-novo-sumoylation
#1
Eva-Maria Schilling, Myriam Scherer, Nina Reuter, Johannes Schweininger, Yves A Muller, Thomas Stamminger
: PML nuclear bodies (NBs) are accumulations of cellular proteins embedded in a scaffold-like structure built by SUMO-modified PML/TRIM19. PML and other NB proteins act as cellular restriction factors against human cytomegalovirus (HCMV), however, this intrinsic defense is counteracted by the immediate-early protein 1 (IE1) of HCMV. IE1 directly interacts with the PML coiled-coil domain via its globular core region and disrupts NB foci by inducing a loss of PML SUMOylation. Here, we demonstrate that IE1 acts via abrogating the de novo SUMOylation of PML...
November 30, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27895727/deficiency-of-sumo-specific-protease-1-induces-arsenic-trioxide-mediated-apoptosis-by-regulating-xbp1-activity-in-human-acute-promyelocytic-leukemia
#2
Fei-Fei Wang, Ming-Zhu Liu, Yi Sui, Qing Cao, Bo Yan, Mei-Ling Jin, Xi Mo
Small ubiquitin-like modifier (SUMO)/sentrin-specific protease 1 (SENP1), a member of the SENP family, is highly expressed in several neoplastic tissues. However, the effect of SENP1 in acute promyelocytic leukemia (APL) has not been elucidated. In the present study, it was observed that SENP1 deficiency had no effect on the spontaneous apoptosis or differentiation of NB4 cells. Arsenic trioxide (As2O3) could induce the upregulation of endoplasmic reticulum (ER) stress, resulting in the apoptosis of NB4 cells...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27892526/comprehensive-gene-expression-meta-analysis-and-integrated-bioinformatic-approaches-reveal-shared-signatures-between-thrombosis-and-myeloproliferative-disorders
#3
Prabhash Kumar Jha, Aatira Vijay, Anita Sahu, Mohammad Zahid Ashraf
Thrombosis is a leading cause of morbidity and mortality in patients with myeloproliferative disorders (MPDs), particularly polycythemia vera (PV) and essential thrombocythemia (ET). Despite the attempts to establish a link between them, the shared biological mechanisms are yet to be characterized. An integrated gene expression meta-analysis of five independent publicly available microarray data of the three diseases was conducted to identify shared gene expression signatures and overlapping biological processes...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27889610/cacul1-cac1-attenuates-p53-activity-through-pml-post-translational-modification
#4
Tomomi Fukuda, Yu Kigoshi-Tansho, Takao Naganuma, Akira Kazaana, Tomomi Okajima, Fuminori Tsuruta, Tomoki Chiba
Promyelocytic leukaemia (PML) is a tumor suppressor protein covalently conjugated with SUMO family proteins, leading to the formation of PML nuclear bodies (NBs). PML-NBs provide a platform for efficient posttranslational modification of targets and protein-protein interaction, contributing to the adjustment of gene expression and chromatin integrity. Although PML SUMOylation is thought to play important roles in diverse cellular functions, the control mechanisms of adequate modification levels have remained unsolved...
November 23, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27882949/sumo-specific-protease-1-protects-neurons-from-apoptotic-death-during-transient-brain-ischemia-reperfusion
#5
Huijun Zhang, Yan Wang, Aoxue Zhu, Dehua Huang, Shining Deng, Jinke Cheng, Michael X Zhu, Yong Li
SUMO-specific protease 1 (SENP1) deconjugates SUMO from modified proteins. Although post-ischemic activation of SUMO conjugation was suggested to be neuroprotective against ischemia/reperfusion (I/R) injury, the function of SENP1 in this process remained unclear. Here we show that transient middle cerebral artery occlusion in mice followed by 6, 12 and 24 h reperfusion significantly enhanced SENP1 levels in the affected brain area, independent of transcription. Consistent with the increase in SENP1, the levels of SUMO1-conjugated proteins were decreased by I/R in cortical neurons of control littermate mice, but unchanged in that of animals with conditional ablation of SENP1 gene from adult principal neurons, the SENP1(flox/flox):CamKIIα-Cre (SENP1 cKO) mice...
November 24, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27876557/targeting-nuclear-thymidylate-biosynthesis
#6
REVIEW
James Chon, Patrick J Stover, Martha S Field
Thymidylate (dTMP) biosynthesis plays an essential and exclusive function in DNA synthesis and proper cell division, and therefore has been an attractive therapeutic target. Folate analogs, known as antifolates, and nucleotide analogs that inhibit the enzymatic action of the de novo thymidylate biosynthesis pathway and are commonly used in cancer treatment. In this review, we examine the mechanisms by which the antifolate 5-fluorouracil, as well as other dTMP synthesis inhibitors, function in cancer treatment in light of emerging evidence that dTMP synthesis occurs in the nucleus...
November 19, 2016: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/27875543/irisin-ameliorates-hypoxia-reoxygenation-induced-injury-through-modulation-of-histone-deacetylase-4
#7
Yu Tina Zhao, Hao Wang, Shouyan Zhang, Jianfeng Du, Shougang Zhuang, Ting C Zhao
Irisin is a recently identified myokine which brings increases in energy expenditure and contributes to the beneficial effects of exercise through the browning of white adipose tissues. However, its effects in the heart remains unknown. This study sought to determine the effects of irisin on hypoxia/reoxygenation injury and its relationship with HDAC4. Wild type and stable HDAC4-overexpression cells were generated from H9c2 cardiomyoblasts. HDAC4 overexpression cells and wild type H9c2 cells were exposed to 24 hours of hypoxia followed by one hour of reoxygenation in vitro in the presence or absence of irisin (5 ng/ml)...
2016: PloS One
https://www.readbyqxmd.com/read/27872982/interplay-between-top1-and-mms21-nse2-mediated-sumoylation-in-stable-maintenance-of-long-chromosomes
#8
Lakshmi Mahendrawada, Ragini Rai, Deepash Kothiwal, Shikha Laloraya
Genetic information in cells is encrypted in DNA molecules forming chromosomes of varying sizes. Accurate replication and partitioning of chromosomes in the crowded cellular milieu is a complex process involving duplication, folding and movement. Longer chromosomes may be more susceptible to mis-segregation or DNA damage and there may exist specialized physiological mechanisms preventing this. Here, we present genetic evidence for such a mechanism which depends on Mms21/Nse2 mediated sumoylation and topoisomerase-1 (Top1) for maintaining stability of longer chromosomes...
November 21, 2016: Current Genetics
https://www.readbyqxmd.com/read/27864857/protein-sumoylation-is-involved-in-cell-cycle-progression-and-cell-morphology-in-giardia-lamblia
#9
Bruno M Di Genova, Richard C da Silva, Júlia P C da Cunha, Pablo R Gargantini, Renato A Mortara, Renata R Tonelli
The unicellular protozoa Giardia lamblia is a food- and waterborne parasite that causes giardiasis. This illness is manifested as acute and self-limited diarrhea and can evolve to long-term complications. Successful establishment of infection by Giardia trophozoites requires adhesion to host cells and colonization of the small intestine, where parasites multiply by mitotic division. The tight binding of trophozoites to host cells occurs by means of the ventral adhesive disc, a spiral array of microtubules and associated proteins such as giardins...
November 19, 2016: Journal of Eukaryotic Microbiology
https://www.readbyqxmd.com/read/27864346/cbx4-suppresses-metastasis-via-recruitment-of-hdac3-to-the-runx2-promoter-in-colorectal-carcinoma
#10
Xin Wang, Liping Li, Yuanzhong Wu, Ruhua Zhang, Meifang Zhang, Dan Liao, Gang Wang, Ge Qin, Rui-Hua Xu, Tiebang Kang
Polycomb chromobox (CBX) proteins participate in the polycomb repressive complex (PRC1) that mediates epigenetic gene silencing and endow PRC1 with distinct oncogenic or tumor suppressor functions in a cell type-dependent manner. In this study, we report that inhibition of cell migration, invasion, and metastasis in colorectal carcinoma (CRC) requires CBX4-mediated repression of Runx2, a key transcription factor that promotes CRC metastasis. CBX4 inversely correlated with Runx2 expression in CRC tissues, and the combination of high CBX4 expression and low Runx2 expression significantly correlated with overall survival, more so than either CBX4 or Runx2 expresson alone...
November 18, 2016: Cancer Research
https://www.readbyqxmd.com/read/27860533/adaptive-aneuploidy-counters-a-dysregulated-sumo-system
#11
Hong-Yeoul Ryu, Mark Hochstrasser
No abstract text is available yet for this article.
November 18, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27853276/sumo-specific-protease-3-is-a-key-regulator-for-hepatic-lipid-metabolism-in-non-alcoholic-fatty-liver-disease
#12
Yuhan Liu, Fudong Yu, Yan Han, Qing Li, Zhujun Cao, Xiaogang Xiang, Shaowen Jiang, Xiaolin Wang, Jie Lu, Rongtao Lai, Hui Wang, Wei Cai, Shisan Bao, Qing Xie
Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in hepatocytes. The role of SENP3 in lipid metabolism, particularly NAFLD, is unclear. Our results showed that hepatic SENP3 was up-regulated in NAFLD patients and an animal model in vivo and after loading hepatocytes with free fatty acids (FFA) in vitro. Intracellular lipid accumulation was determined in SENP3 silenced or overexpressed hepatocytes with/without FFA in vitro. Confirming a role for SENP3, gene silencing was associated in vitro with amelioration of lipid accumulation and overexpression with enhancement of lipid accumulation...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27852949/transcriptional-gene-silencing-maintained-by-ots1-sumo-protease-requires-a-polymerase-v-dependent-pathway
#13
Lei Liu, Xiaojing Yan, Xiang Xiong Kong, Yiqiang Zhao, Zhizhong Gong, Jing Bo Jin, Yan Guo
The expression of genes with aberrant structure is prevented at both transcriptional- and posttranscriptional-regulation levels. Aberrant gene silencing at posttranscriptional level is well studied, however, it is not well understood how aberrant genes are silenced at transcriptional level. In this study, through genetic screening a transgenic report line that harbors an aberrant gene (35S-LUC, lacking 3'-UTR) and lacks luciferase (LUC) activity, we identify that the SUMO protease OTS1 gene is required for maintaining the silence of the reporter 35S-LUC and an endogenous mutator-like element MULE-F19G14 at transcriptional level, which requires Pol V and DDR complex, but not Pol IV...
November 16, 2016: Plant Physiology
https://www.readbyqxmd.com/read/27852060/senp1-regulates-pten-stability-to-dictate-prostate-cancer-development
#14
Tasneem Bawa-Khalfe, Feng-Ming Yang, Joan Ritho, Hui-Kuan Lin, Jinke Cheng, Edward T H Yeh
SUMO protease SENP1 is elevated in multiple carcinomas including prostate cancer (PCa). SENP1 exhibits carcinogenic properties; it promotes androgen receptor-dependent and -independent cell proliferation, stabilizes HIF1α, increases VEGF, and supports angiogenesis. However, mice expressing an androgen-responsive promoter driven SENP1-transgene (SENP1-Tg) develop high-grade prostatic intraepithelial neoplasia, but not carcinoma. We now show that tumor suppressive PTEN signaling is induced in SENP1-Tg to enhance prostate epithelial cell apoptosis...
November 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27849047/regulation-of-ebola-virus-vp40-matrix-protein-by-sumo
#15
Maite Baz-Martínez, Ahmed El Motiam, Paula Ruibal, Gabriela N Condezo, Carlos F de la Cruz-Herrera, Valerie Lang, Manuel Collado, Carmen San Martín, Manuel S Rodríguez, Cesar Muñoz-Fontela, Carmen Rivas
The matrix protein of Ebola virus (EBOV) VP40 regulates viral budding, nucleocapsid recruitment, virus structure and stability, viral genome replication and transcription, and has an intrinsic ability to form virus-like particles. The elucidation of the regulation of VP40 functions is essential to identify mechanisms to inhibit viral replication and spread. Post-translational modifications of proteins with ubiquitin-like family members are common mechanisms for the regulation of host and virus multifunctional proteins...
November 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27847303/sumoylation-of-large-tumor-suppressor-1-at-lys751-attenuates-its-kinase-activity-and-tumor-suppressor-functions
#16
Liu Mei, Lianwen Yuan, Wei Shi, Shihao Fan, Chao Tang, Xueying Fan, Wanlei Yang, Yu Qian, Musaddique Hussain, Ximei Wu
Large tumor suppressor (Lats) plays a critical role in maintaining cellular homeostasis and is the core to mediate Hippo growth-inhibitory signaling pathway. SUMOylation is a reversible and dynamic process that regulates a variety of cell functions. Here, we show that SUMOylation of Lats1 affects its kinase activity specifically towards Hippo signaling. Small ubiquitin-like modifier (SUMO) 1 interacts with and directly SUMOylates Lats1, whereas loss of SUMOylation pathway function disrupts Lats1 SUMOylation...
November 12, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27843805/impaired-repressor-function-in-sumoylation-defective-thyroid-hormone-receptor-isoforms
#17
Joachim M Weitzel
BACKGROUND: Many nuclear receptors are modified by posttranslational modifications. OBJECTIVES: The transcriptional activity of thyroid hormone receptors (TRs) is modified by the influence of its ligand (thyroid hormones T3 and T4), but is also affected by posttranslational modifications. This study focuses on the SUMOylation of TR isoforms and the consequences on transcriptional activity and promoter occupancy. METHODS: SUMOylation of TR wild-type as well as isoform-specific point mutations have been studied in vitro...
September 2016: European Thyroid Journal
https://www.readbyqxmd.com/read/27833854/human-promyelocytic-leukemia-protein-is-targeted-to-distinct-subnuclear-domains-in-plant-nuclei-and-colocalizes-with-nucleolar-constituents-in-a-sumo-dependent-manner
#18
Christian E Lamm, Myriam Scherer, Nina Reuter, Bushra Amin, Thomas Stamminger, Uwe Sonnewald
Eukaryotic nuclei are subdivided into subnuclear structures. Among the most prominent of these structures are the nucleolus and the PML nuclear bodies (PML-NBs). PML-NBs are spherical multiprotein aggregates of varying size localized in the interchromosomal area. PML-NB formation is dependent on the presence of the promyelocytic leukemia protein (PML) as well as on post-translational modification of core components by covalent attachment of the small ubiquitin-like modifier (SUMO). So far, PML-NBs as well as PML have been described in mammalian cells only, whereas no orthologs are known in the plant kingdom...
November 2016: FEBS Open Bio
https://www.readbyqxmd.com/read/27826860/analysis-of-sumoylation-in-the-rent-complex-by-fusion-to-a-sumo-specific-protease-domain
#19
Neus Colomina, Clàudia Guasch, Jordi Torres-Rosell
Protein sumoylation is a reversible posttranslational modification that controls multiple processes during cell cycle progression. Frequently, SUMO synergistically targets various subunits in a protein complex to modulate its function, leading to what has been defined as protein group sumoylation. Different subunits in the RENT (regulator of nucleolar silencing and telophase) complex, including Net1, Sir2, and Cdc14, can be coupled to SUMO, making it difficult to ascertain the role of this modification. Here we describe a method to downregulate sumoylation in RENT, consisting in the fusion of a catalytic domain of the Ulp1 SUMO protease (Ulp Domain; UD) to the C-terminus of members in the complex using epitope tags as linkers...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27819299/several-posttranslational-modifications-act-in-concert-to-regulate-gephyrin-scaffolding-and-gabaergic-transmission
#20
Himanish Ghosh, Luca Auguadri, Sereina Battaglia, Zahra Simone Thirouin, Khaled Zemoura, Simon Messner, Mario A Acuña, Hendrik Wildner, Gonzalo E Yévenes, Andrea Dieter, Hiroshi Kawasaki, Michael O Hottiger, Hanns Ulrich Zeilhofer, Jean-Marc Fritschy, Shiva K Tyagarajan
GABAA receptors (GABAARs) mediate the majority of fast inhibitory neurotransmission in the brain via synergistic association with the postsynaptic scaffolding protein gephyrin and its interaction partners. However, unlike their counterparts at glutamatergic synapses, gephyrin and its binding partners lack canonical protein interaction motifs; hence, the molecular basis for gephyrin scaffolding has remained unclear. In this study, we identify and characterize two new posttranslational modifications of gephyrin, SUMOylation and acetylation...
November 7, 2016: Nature Communications
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