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SUMOylation

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https://www.readbyqxmd.com/read/27904679/tongxinluo-inhibits-neointimal-formation-by-regulating-the-expression-and-post-translational-modification-of-klf5-in-macrophages
#1
Wen Jiang, Bin Zheng, Xin-Hua Zhang, Ling-Yan Yue, Chan Liu, Dong Ma, Zhan Yang, Jin-Kun Wen
Neointimal hyperplasia is a common pathological characteristic in diverse vascular remodeling diseases. The inflammatory response that follows vascular injury plays an important role in intimal hyperplasia. Tongxinluo (TXL), a traditional Chinese medicine, can ameliorate neointimal formation via suppressing vascular inflammatory response induced by vascular injury. However, the mechanisms underlying anti-inflammatory and anti-intimal hyperplasia of TXL are still not fully understood. The aim of present study was to examine whether the expression and post-translational modification of KLF5 were involved in the vasoprotective effects of TXL...
2016: American Journal of Translational Research
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
#2
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/27897116/the-molecular-mechanisms-and-the-role-of-hnrnp-k-protein-post-translational-modification-in-dna-damage-repair
#3
Jing Lu, Feng-Hou Gao
DNA damage repair is a kind of cellular self-protection mechanism that some relevant proteins are activated when DNA damage response happens in order to maintain the intracellular function stability and structure integrity. Post-translational modifications (PTMs) of proteins can rapidly confers to them more complicated structure and sophisticated function by covalently combining with different small molecules with target proteins, which in turn plays an important regulatory role in DNA damage repair. It was reported that heterogeneous nuclear ribonucleoprotein K (hnRNP K) could be involved in DNA damage repair process under the regulation of its many post-translational modifications, including methylation, ubiquitination, sumoylation and phosphorylation...
November 29, 2016: Current Medicinal Chemistry
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
#4
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/27894240/sumoylation-regulation-of-retina-development-and-functions
#5
L Zhang, D W-C Li
The structure and developmental mechanisms of vertebrate retina are highly conserved. One of the most distinctive events during retinogenesis is the temporally and spatially generation of seven types of retinal cells from the multipotent retinal progenitor cells. The importance and prevalence of SUMOylation in regulation of this process through modulation of gene expression and protein function diversity have been increasingly appreciated. Here, we review the biological significance of SUMOylation in retina development, examine how SUMOylation balances the proliferation and cell cycle exit of retinal progenitor cells, and finally discuss the molecular mechanisms mediating the specification of different retina neurons and photoreceptors through modulation of various transcription factors...
November 28, 2016: Current Molecular Medicine
https://www.readbyqxmd.com/read/27892526/comprehensive-gene-expression-meta-analysis-and-integrated-bioinformatic-approaches-reveal-shared-signatures-between-thrombosis-and-myeloproliferative-disorders
#6
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
#7
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/27885874/post-translational-regulation-of-neuronal-nitric-oxide-synthase-implications-for-sympathoexcitatory-states
#8
Neeru M Sharma, Kaushik P Patel
Nitric oxide (NO) synthesized via neuronal nitric oxide synthase (nNOS) plays a significant role in regulation/modulation of autonomic control of circulation. Various pathological states are associated with diminished nNOS expression and blunted autonomic effects of NO in the central nervous system (CNS) including heart failure, hypertension, diabetes mellitus, chronic renal failure etc. Therefore, elucidation of the molecular mechanism/s involved in dysregulation of nNOS is essential to understand the pathogenesis of increased sympathoexcitation in these diseased states...
December 2, 2016: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/27885627/enzyme-complexes-important-for-the-glutamate-glutamine-cycle
#9
Mary C McKenna, Gustavo C Ferreira
Transient multienzyme and/or multiprotein complexes (metabolons) direct substrates toward specific pathways and can significantly influence the metabolism of glutamate and glutamine in the brain. Glutamate is the primary excitatory neurotransmitter in brain. This neurotransmitter has essential roles in normal brain function including learning and memory. Metabolism of glutamate involves the coordinated activity of astrocytes and neurons and high affinity transporter proteins that are selectively distributed on these cells...
2016: Advances in Neurobiology
https://www.readbyqxmd.com/read/27878232/involvement-of-bleomycin-hydrolase-and-poly-adp-ribose-polymerase-1-in-ubc9-mediated-resistance-to-chemotherapy-agents
#10
Yang Chen, Huixian Zhang, Qiyang He
Ubiquitin-conjugating protein 9 (Ubc9), the sole enzyme for sumoylation, plays critical roles in many physiological functions, such as DNA damage repair and genome integrity. Its overexpression led to poor prognosis and drug resistance in tumor chemotherapy. However, the underlying mechanism by which Ubc9 promotes tumor progress and influences the susceptibility to antitumor agents remains elusive. In this study, we used nine antitumor agents with distinct actions to explore Ubc9-mediated resistance in human breast carcinoma MCF-7 cells...
November 23, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27876557/targeting-nuclear-thymidylate-biosynthesis
#11
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/27875680/sumoylation-stabilizes-smoothened-to-promote-hedgehog-signaling
#12
Yun Qi, Han Liu, Xinhua Lin
The conserved Hedgehog signaling pathway is essential for embryonic development and tissue homeostasis and is tightly regulated. In this issue of Developmental Cell, Ma et al. (2016) demonstrate that sumoylation works in parallel with phosphorylation to stabilize Smoothened, antagonizing its ubiquitination and subsequent degradation, thus activating Hh target gene transcription.
November 21, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27875274/sirt1-inhibits-ev71-genome-replication-and-rna-translation-by-interfering-viral-polymerase-and-5-utr-rna
#13
Yang Han, Lvyin Wang, Jin Cui, Yu Song, Zhen Luo, Junbo Chen, Ying Xiong, Qi Zhang, Fang Liu, Wenzhe Ho, Yingle Liu, Kailang Wu, Jianguo Wu
Enterovirus 71 (EV71) possesses a single-stranded positive RNA genome that contains a single open reading frame (ORF) flanked by a 5'untranslated region (5'UTR) and a polyadenylated 3'UTR. Here, we demonstrated that EV71 activates the production of silent mating type information regulation 2 homolog 1 (SIRT1), a histone deacetylase (HDAC). EV71 further stimulates SIRT1 sumoylation and deacetylase activity, and enhances SIRT1 translocation from nuclear to cytoplasm. More interestingly, activated SIRT1 subsequently binds with EV71 3D protein (a viral RNA-dependent RNA polymerase, RdRp) to repress the acetylation and RdRp activity of 3D, resulting in the attenuation of viral genome replication...
November 14, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27872982/interplay-between-top1-and-mms21-nse2-mediated-sumoylation-in-stable-maintenance-of-long-chromosomes
#14
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
#15
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/27852949/transcriptional-gene-silencing-maintained-by-ots1-sumo-protease-requires-a-polymerase-v-dependent-pathway
#16
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
#17
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
#18
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
#19
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
#20
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
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