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SUMOylation

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https://www.readbyqxmd.com/read/28648619/nuclear-import-of-glucokinase-in-pancreatic-beta-cells-is-mediated-by-a-nuclear-localization-signal-and-modulated-by-sumoylation
#1
Bente Berg Johansson, Karianne Fjeld, Marie Holm Solheim, Jun Shirakawa, Enming Zhang, Magdalena Keindl, Jiang Hu, Andreas Lindqvist, Anne Døskeland, Gunnar Mellgren, Torgeir Flatmark, Pål Rasmus Njølstad, Rohit N Kulkarni, Nils Wierup, Ingvild Aukrust, Lise Bjørkhaug
The localization of glucokinase in pancreatic beta-cell nuclei is a controversial issue. Although previous reports suggest such a localization, the mechanism for its import has so far not been identified. Using immunofluorescence, subcellular fractionation and mass spectrometry, we here present evidence in support of glucokinase localization in beta-cell nuclei of human and mouse pancreatic sections, as well as in human and mouse isolated islets, and murine MIN6 cells. We have identified a conserved, seven-residue nuclear localization signal ((30)LKKVMRR(36)) in the human enzyme...
June 22, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28639696/modulation-of-global-sumoylation-by-kaposi-s-sarcoma-associated-herpesvirus-and-its-effects-on-viral-gene-expression
#2
Jinzhong Wang, Yuying Guo, Xu Wang, Rui Zhao, Ying Wang
Some viruses have evolved to exploit the host SUMOylation system to regulate their own replication. Kaposi's sarcoma-associated herpesvirus (KSHV) encodes K-bZIP, a SUMO E3 ligase catalyzing the SUMOylation of viral and host proteins. KSHV also encodes replication and transcriptional activator (RTA), a SUMO-targeted ubiquitin ligase catalyzing the ubiquitination of SUMOylated proteins and targeting them for degradation. Using chronic KSHV-infected TRE × BCBL-1 RTA cells, the expression kinetics of K-bZIP and RTA, and the global SUMOylation level were detected...
June 22, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28637749/cell-cycle-dependent-spatial-segregation-of-telomerase-from-sites-of-dna-damage
#3
Faissal Ouenzar, Maxime Lalonde, Hadrien Laprade, Geneviève Morin, Franck Gallardo, Samuel Tremblay-Belzile, Pascal Chartrand
Telomerase can generate a novel telomere at DNA double-strand breaks (DSBs), an event called de novo telomere addition. How this activity is suppressed remains unclear. Combining single-molecule imaging and deep sequencing, we show that the budding yeast telomerase RNA (TLC1 RNA) is spatially segregated to the nucleolus and excluded from sites of DNA repair in a cell cycle-dependent manner. Although TLC1 RNA accumulates in the nucleoplasm in G1/S, Pif1 activity promotes TLC1 RNA localization in the nucleolus in G2/M...
June 21, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28630323/role-of-the-cbp-catalytic-core-in-intramolecular-sumoylation-and-control-of-histone-h3-acetylation
#4
Sangho Park, Robyn L Stanfield, Maria A Martinez-Yamout, H Jane Dyson, Ian A Wilson, Peter E Wright
The histone acetyl transferases CREB-binding protein (CBP) and its paralog p300 play a critical role in numerous cellular processes. Dysregulation of their catalytic activity is associated with several human diseases. Previous work has elucidated the regulatory mechanisms of p300 acetyltransferase activity, but it is not known whether CBP activity is controlled similarly. Here, we present the crystal structure of the CBP catalytic core encompassing the bromodomain (BRD), CH2 (comprising PHD and RING), HAT, and ZZ domains at 2...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28630282/desumoylation-of-gli1-by-senp1-attenuates-sonic-hedgehog-signaling
#5
Huaize Liu, Sen Yan, Jie Ding, Ting-Ting Yu, Steven Y Cheng
Transcriptional output of the Sonic hedgehog morphogenic pathway is orchestrated by three Krüppel family transcription factors, Gli1-3, which undergo extensive post-translational modifications, including ubiquitination and SUMOylation. Here, we report that sentrin-specific peptidase SENP1 is the specific de-SUMOylation enzyme for Gli1. We show that SUMOylation stabilizes Gli1 by competing with ubiquitination at conserved lysine residues, and SUMOylated Gli1 is enriched in the nucleus, suggesting that SUMOylation is a nuclear localization signal for Gli1...
June 19, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28622293/sumo-triggered-ubiquitination-of-nr4a1-controls-macrophage-cell-death
#6
Long Zhang, Feng Xie, Juan Zhang, Peter Ten Dijke, Fangfang Zhou
Nuclear receptor NR4A1 has been implicated as a key regulator in a wide range of pathophysiological responses. As an immediate early response gene, NR4A1 can be rapidly and potently induced by a variety of stimuli. Its induction is followed by its rapid degradation, but the mechanism by which NR4A1 is degraded remains poorly understood. Here we show that nuclear receptor NR4A1 is sumoylated by SUMO2/3. Upon poly-SUMO modification, NR4A1 can be targeted by the SUMO-dependent E3 ubiquitin ligase RNF4 for polyubiquitination and subsequent degradation...
June 16, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28621413/the-sumo-system-in-caenorhabditis-elegans-development
#7
Limor Broday
SUMO, a small ubiquitin-like modifier, is a highly conserved post translational modification and a central regulatory system in eukaryotes. Sumoylation modulates the activities of multiple proteins, mainly in the nucleus, such as transcription factors, chromatin modifiers, and proteins involved in DNA replication and repair. However, SUMO also modifies substrates in the cytoplasm, mitochondria, plasma and ER membrane. This review summarizes our current knowledge on the functions of sumoylation in C. elegans development...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28620180/a-functional-sumo-motif-in-the-active-site-of-pim1-promotes-its-degradation-via-rnf4-and-stimulates-protein-kinase-activity
#8
R Sumanth Iyer, Lynsey Chatham, Roger Sleigh, David W Meek
The PIM1 serine/threonine protein kinase mediates growth factor and survival signalling, and cooperates potently with c-MYC during tumorigenesis. PIM1 is overexpressed in many human cancers and is a promising target for drug development. PIM1 levels are regulated mainly through cytokine-induced transcription and protein degradation, but mechanisms regulating its activity and levels remain largely unexplored. Here, we show that PIM1 is modified in vitro and in cultured cells by the Small ubiquitin-like modifier (SUMO) on two independent sites: K169, within a consensus SUMOylation motif (IK(169)DE(171)) in the active site of PIM1, and also at a second promiscuous site...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28615201/the-latency-associated-nuclear-antigen-of-kaposi-s-sarcoma-associated-herpesvirus-inhibits-expression-of-sumo-sentrin-specific-peptidase-6-to-facilitate-latency-establishment
#9
Xiaoxi Lin, Rui Sun, Fang Zhang, Yuan Gao, Lianghua Bin, Ke Lan
Kaposi's sarcoma-associated herpesvirus (KSHV), belonging to γ-herpesviridae, typically displays two different phases in its lifecycle, the latent phase and the lytic phase. Latent-associated nuclear antigen (LANA), the primary viral product during latency, has been reported to bind to a series of cellular gene promoters to modulate gene transcription. To systemically elucidate the cellular genes regulated by LANA, we identified genome-wide LANA binding sites by chromatin immunoprecipitation coupled with sequencing (ChIP-seq)...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28598330/analysis-of-sumo1-conjugation-at-synapses
#10
James A Daniel, Benjamin H Cooper, Jorma J Palvimo, Fu-Ping Zhang, Nils Brose, Marilyn Tirard
SUMO1-conjugation of proteins at neuronal synapses is considered to be a major post-translational regulatory process in nerve cell and synapse function, but the published evidence for SUMO1-conjugation at synapses is contradictory. We employed multiple genetic mouse models for stringently controlled biochemical and immunostaining analyses of synaptic SUMO1-conjugation. By using a knock-in reporter mouse line expressing tagged SUMO1, we could not detect SUMO1-conjugation of seven previously proposed synaptic SUMO1-targets in the brain...
June 9, 2017: ELife
https://www.readbyqxmd.com/read/28595951/sumoylation-regulates-the-transcriptional-activity-of-different-human-nfat-isoforms-in-neurons
#11
Hanna Vihma, Tõnis Timmusk
In the nervous system, four calcium/calcineurin-regulated members of the nuclear factor of activated T-cells (NFAT) family of transcription factors, NFATc1-c4, are involved in many developmental and functional processes, such as corticogenesis, synaptogenesis, synaptic plasticity and neurotransmission, that all need precise gene regulation. Therefore it is important to understand molecular events that contribute to the regulation of the transcriptional activity of specific NFAT isoforms. Previously, we have shown that there are a number of alternative splice variants of NFAT genes expressed in the brain and that neuronal activity leads to isoform-specific transactivation capacities of different human NFAT proteins...
June 10, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28589199/the-strategies-for-identification-and-quantification-of-sumoylation
#12
Yan Zhang, Yueying Li, Bo Tang, Chun-Yang Zhang
SUMOylation is a post-translational modification that plays critical roles in a multitude of cellular processes including transcription, cellular localization, DNA repair and cell cycle progression. Similar to ubiquitin, the small ubiquitin-like modifiers (SUMOs) are covalently attached to the epsilon amino group of lysine residues in the substrates. To understand the regulation and the dynamics of post-translational modifications (PTMs), the identification and quantification of SUMOylation is strictly needed...
June 7, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28588610/ubiquitination-and-sumoylation-in-telomere-maintenance-and-dysfunction
#13
REVIEW
Zeliha Yalçin, Carolin Selenz, Jacqueline J L Jacobs
Telomeres are essential nucleoprotein structures at linear chromosomes that maintain genome integrity by protecting chromosome ends from being recognized and processed as damaged DNA. In addition, they limit the cell's proliferative capacity, as progressive loss of telomeric DNA during successive rounds of cell division eventually causes a state of telomere dysfunction that prevents further cell division. When telomeres become critically short, the cell elicits a DNA damage response resulting in senescence, apoptosis or genomic instability, thereby impacting on aging and tumorigenesis...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28587922/molecular-basis-for-k63-linked-ubiquitination-processes-in-double-strand-dna-break-repair-a-focus-on-kinetics-and-dynamics
#14
REVIEW
Brian L Lee, Anamika, J N Mark Glover, Michael J Hendzel, Leo Spyracopoulos
Cells are exposed to thousands of DNA damage events on a daily basis. This damage must be repaired to preserve genetic information, and prevent development of disease. The most deleterious damage is a double strand break (DSB), which is detected and repaired by mechanisms known as non-homologous end joining (NHEJ), and homologous recombination (HR), components of the DNA damage response system. NHEJ is an error prone first line of defense, whereas HR invokes error free repair, and is the focus of this review...
June 3, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28582471/sumo-regulates-p21cip1-intracellular-distribution-and-with-p21cip1-facilitates-multiprotein-complex-formation-in-the-nucleolus-upon-dna-damage
#15
Sonia Brun, Neus Abella, Maria T Berciano, Olga Tapia, Montserrat Jaumot, Raimundo Freire, Miguel Lafarga, Neus Agell
We previously showed that p21Cip1 transits through the nucleolus on its way from the nucleus to the cytoplasm and that DNA damage inhibits this transit and induces the formation of p21Cip1-containing intranucleolar bodies (INoBs). Here, we demonstrate that these INoBs also contain SUMO-1 and UBC9, the E2 SUMO-conjugating enzyme. Furthermore, whereas wild type SUMO-1 localized in INoBs, a SUMO-1 mutant, which is unable to conjugate with proteins, does not, suggesting the presence of SUMOylated proteins at INoBs...
2017: PloS One
https://www.readbyqxmd.com/read/28576968/localisation-of-nup153-and-senp1-to-nuclear-pore-complexes-is-required-for-53bp1-mediated-dna-double-strand-break-repair
#16
Vincent Duheron, Nadine Nilles, Sylvia Pecenko, Valérie Martinelli, Birthe Fahrenkrog
The nuclear basket of nuclear pore complexes (NPCs) is composed of three nucleoporins: Nup153, Nup50 and Tpr. Nup153 has a role in DNA double-strand break (DSB) repair by promoting nuclear import of 53BP1, a mediator of DNA damage response. Here we provide evidence that loss of Nup153 compromises 53BP1 sumoylation, prerequisite for efficient accumulation of 53BP1 at DSBs. Depletion of Nup153 resulted in reduced SUMO1 modification of 53BP1 and the displacement of the SUMO protease SENP1 from NPCs. Artificial tethering of SENP1 to NPCs restored non-homologous end joining (NHEJ) in the absence of Nup153 and re-established 53BP1 sumoylation...
June 2, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28572537/down-regulation-of-ubc9-increases-the-sensitivity-of-hepatocellular-carcinoma-to-doxorubicin
#17
Sufen Fang, Junyao Qiu, Zheng Wu, Tao Bai, Wuhua Guo
UBC9 is an E2-conjugating enzyme that is required for SUMOylation and has been implicated in regulating several critical cellular pathways. UBC9 is overexpressed in certain tumors, such as lung adenocarcinoma, ovarian carcinoma and melanoma, which implies that it has special clinical significance. However, the role of UBC9 in Hepatocellular carcinoma (HCC) drug responsiveness is not clear. In this study, we investigated the clinicopathological significance of UBC9 in HCC and investigated the mechanism of UBC9-mediated chemosensitivity to doxorubicin (DOX) in hepatocellular carcinoma cells...
May 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28571744/kr-pok-zbtb7c-regulates-cancer-cell-proliferation-through-glutamine-metabolism
#18
Man-Wook Hur, Jae-Hyeon Yoon, Min-Young Kim, Hyeonseok Ko, Bu-Nam Jeon
Kr-POK (ZBTB7c) is a kidney cancer-related POK transcription factor that not only represses transcription of CDKN1A but also increases expression of FASN. However, precisely how Kr-POK affects cell metabolism by controlling gene expression in response to an energy source in rapidly proliferating cells remains unknown. In this study, we characterized the molecular and functional features of Kr-POK in the context of tumor growth and glutamine metabolism. We found that cells expressing Kr-POK shRNA exhibited more severe cell death than control cells in glucose-deprived medium, and that knockdown of Kr-POK decreased glutamine uptake...
May 30, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28569748/the-critical-role-of-senp1-mediated-gata2-desumoylation-in-promoting-endothelial-activation-in-graft-arteriosclerosis
#19
Cong Qiu, Yuewen Wang, Haige Zhao, Lingfeng Qin, Yanna Shi, Xiaolong Zhu, Lin Song, Xiaofei Zhou, Jian Chen, Hong Zhou, Haifeng Zhang, George Tellides, Wang Min, Luyang Yu
Data from clinical research and our previous study have suggested the potential involvement of SENP1, the major protease of post-translational SUMOylation, in cardiovascular disorders. Here, we investigate the role of SENP1-mediated SUMOylation in graft arteriosclerosis (GA), the major cause of allograft failure. We observe an endothelial-specific induction of SENP1 and GATA2 in clinical graft rejection specimens that show endothelial activation-mediated vascular remodelling. In mouse aorta transplantation GA models, endothelial-specific SENP1 knockout grafts demonstrate limited neointima formation with attenuated leukocyte recruitment, resulting from diminished induction of adhesion molecules in the graft endothelium due to increased GATA2 SUMOylation...
June 1, 2017: Nature Communications
https://www.readbyqxmd.com/read/28559058/structure-activity-relationships-for-flavone-interactions-with-amyloid-%C3%AE-reveal-a-novel-anti-aggregatory-and-neuroprotective-effect-of-2-3-4-trihydroxyflavone-2-d08
#20
Dylan T Marsh, Sukanya Das, Jessica Ridell, Scott D Smid
Naturally-occurring flavonoids have well documented anti-aggregatory and neuroprotective properties against the hallmark toxic protein in Alzheimer's disease, amyloid β (Aβ). However the extensive diversity of flavonoids has limited the insight into the precise structure-activity relationships that confer such bioactive properties against the Aβ protein. In the present study we have characterised the Aβ binding properties, anti-aggregatory and neuroprotective effects of a discreet set of flavones, including the recently described novel protein sumoylation inhibitor 2',3',4'-trihydroxyflavone (2-D08)...
May 19, 2017: Bioorganic & Medicinal Chemistry
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