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SUMOylation

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https://www.readbyqxmd.com/read/28806398/lysine-52-stabilizes-the-myc-oncoprotein-through-an-scf-fbxw7-independent-mechanism
#1
J De Melo, S S Kim, C Lourenco, L Z Penn
The oncogenic transcription factor c-MYC (MYC) is deregulated and often overexpressed in more than 50% of cancers. MYC deregulation is associated with poor prognosis and aggressive disease, suggesting that the development of therapeutic inhibitors targeting MYC would markedly impact patient outcome. MYC is highly regulated, with a protein and mRNA half-life of ~30 min. The most extensively studied pathway regulating MYC protein stability involves ubiquitylation and proteasomal degradation mediated by the E3-ligase, SCF(Fbxw7)...
August 14, 2017: Oncogene
https://www.readbyqxmd.com/read/28791404/betulinic-acid-increases-radiosensitization-of-oral-squamous-cell-carcinoma-through-inducing-sp1-sumoylation-and-pten-expression
#2
Dao-Ying Yuan, Zhen Meng, Kai Xu, Qiao-Feng Li, Cheng Chen, Ke-Yi Li, Bin Zhang
Radiotherapy is one of the most effective non-surgical treatments for oral squamous cell carcinoma. However, radioresistance remains a major impediment to radiotherapy. Although BetA (Betulinic acid) can induce radiosensitization, the underlying mechanism and whether it could induce radiosensitization in oral squamous cell carcinoma are not fully understood. In this study, we showed that BetA increased radiosensitization in CAL-27 and Tca-83 cells. Radiation-triggered Sp1 overexpression was responsible for radioresistance of OSCC (oral squamous cell carcinoma) cells...
August 3, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28770041/stromal-senp1-promotes-mouse-early-folliculogenesis-by-regulating-bmp4-expression
#3
Shu Tan, Boya Feng, Mingzhu Yin, Huanjiao Jenny Zhou, Ge Lou, Weidong Ji, Yonghao Li, Wang Min
BACKGROUND: Mammalian folliculogenesis, maturation of the ovarian follicles, require both growth factors derived from oocyte and surrounding cells, including stromal cells. However, the mechanism by which stromal cells and derived factors regulate oocyte development remains unclear. RESULTS: We observed that SENP1, a small ubiquitin-related modifier (SUMO)-specific isopeptidase, was expressed in sm22α-positive stromal cells of mouse ovary. The sm22α-positive stromal cells tightly associated with follicle maturation...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28760777/sumoylation-negatively-regulates-angiogenesis-by-targeting-endothelial-notch-signaling
#4
Xiaolong Zhu, Sha Ding, Cong Qiu, Yanna Shi, Lin Song, Yueyue Wang, Yuewen Wang, Jinying Li, Yiran Wang, Yi Sun, Lingfeng Qin, Jun Chen, Michael Simons, Wang Min, Luyang Yu
Rationale: The highly conserved NOTCH signaling pathway functions as a key cell-cell interaction mechanism controlling cell-fate and tissue patterning, while its dysregulation is implicated in a variety of developmental disorders and cancers. The pivotal role of endothelial NOTCH in regulation of angiogenesis is widely appreciated; however, little is known about what controls it signal transduction. Our previous study indicated the potential role of post-translational small ubiquitin-like modifier (SUMO) modification (SUMOylation) in vascular disorders...
July 31, 2017: Circulation Research
https://www.readbyqxmd.com/read/28754290/molecular-epigenetic-targets-for-liver-diseases-current-challenges-and-future-prospects
#5
REVIEW
Robert Zeidler, Bruno Leonardo de Freitas Soares, Augustinus Bader, Shibashish Giri
Advanced chemotherapy fails to treat liver cancer but recent progress in understanding epigenetic modifications have witnessed promising clinical outcomes. Epigenetic alteration is the alteration of epigenomes (surrounding histone proteins) without changing the DNA sequence. Such epigenetic mechanisms include histone modifications such as methylation, acetylation, phosphorylation and sumoylation followed by changes in the genomic architecture. Current studies involving the understanding of small RNA molecules such as noncoding RNA and microRNA in modulating the chromatin architecture are explained in depth here, along with effects of some novel compounds from recent preclinical and clinical evidence...
July 25, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28747610/retraction-protective-effect-of-senp3-mediated-sumoylation-against-cadmium-toxicity
#6
Hongquan Zhu
[This retracts the article DOI: 10.2131/jts.42.233.].
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28747609/increased-sumo-2-3-ylation-mediated-by-senp3-degradation-is-protective-against-cadmium-induced-caspase-3-dependent-cytotoxicity
#7
Jia Luo, Sonam Gurung, Laura Lee, Jeremy M Henley, Kevin A Wilkinson, Chun Guo
Increased post-translational modification of proteins by SUMO-2/3 is a cytoprotective response against cell stress induced by ischaemia and reperfusion. However, it is still unclear what other cell stressors trigger protein SUMOylation, what mechanisms enhance and maintain the enhanced SUMOylation, and if it is a general protective mediator against other cytotoxic stresses. Here, we show increased levels of SUMOylation and decreased levels of the SUMO deconjugating enzyme SENP3 in PC12 cells treated with the toxic heavy metal cadmium...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28744851/post-translational-regulation-of-antiviral-innate-signaling
#8
REVIEW
Yilong Zhou, Chenxi He, Wang Lin, Baoxue Ge
The innate immune system initiates immune responses by pattern-recognition receptors (PRR). Virus-derived nucleic acids are sensed by the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family and the toll-like receptor (TLR) family as well as the DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS). These receptors activate IRF3/7 and NF-κB signaling pathways to induce the expression of type I interferons (IFNs) and other cytokines firing antiviral responses within the cell. However, to achieve a favorable outcome for the host, a balanced production of IFNs and activation of antiviral responses is required...
July 26, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28743749/sumoylation-determines-the-voltage-required-to-activate-cardiac-iks-channels
#9
Dazhi Xiong, Tian Li, Hui Dai, Anthony F Arena, Leigh D Plant, Steve A N Goldstein
IKs channels open in response to depolarization of the membrane voltage during the cardiac action potential, passing potassium ions outward to repolarize ventricular myocytes and end each beat. Here, we show that the voltage required to activate IKs channels depends on their covalent modification by small ubiquitin-like modifier (SUMO) proteins. IKs channels are comprised of four KCNQ1 pore-forming subunits, two KCNE1 accessory subunits, and up to four SUMOs, one on Lys424 of each KCNQ1 subunit. Each SUMO shifts the half-maximal activation voltage (V1/2) of IKs ∼ +8 mV, producing a maximal +34-mV shift in neonatal mouse cardiac myocytes or Chinese hamster ovary (CHO) cells expressing the mouse or human subunits...
July 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28743452/transcriptional-profiles-for-distinct-aggregation-states-of-mutant-huntingtin-exon-1-protein-unmask-new-huntington-s-disease-pathways
#10
Nagaraj S Moily, Angelique R Ormsby, Aleksandar Stojilovic, Yasmin M Ramdzan, Jeannine Diesch, Ross D Hannan, Michelle S Zajac, Anthony J Hannan, Alicia Oshlack, Danny M Hatters
Huntington's disease is caused by polyglutamine (polyQ)-expansion mutations in the CAG tandem repeat of the Huntingtin gene. The central feature of Huntington's disease pathology is the aggregation of mutant Huntingtin (Htt) protein into micrometer-sized inclusion bodies. Soluble mutant Htt states are most proteotoxic and trigger an enhanced risk of death whereas inclusions confer different changes to cellular health, and may even provide adaptive responses to stress. Yet the molecular mechanisms underpinning these changes remain unclear...
July 23, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28740167/dna-end-resection-requires-constitutive-sumoylation-of-ctip-by-cbx4
#11
Isabel Soria-Bretones, Cristina Cepeda-García, Cintia Checa-Rodriguez, Vincent Heyer, Bernardo Reina-San-Martin, Evi Soutoglou, Pablo Huertas
DNA breaks are complex DNA lesions that can be repaired by two alternative mechanisms: non-homologous end-joining and homologous recombination. The decision between them depends on the activation of the DNA resection machinery, which blocks non-homologous end-joining and stimulates recombination. On the other hand, post-translational modifications play a critical role in DNA repair. We have found that the SUMO E3 ligase CBX4 controls resection through the key factor CtIP. Indeed, CBX4 depletion impairs CtIP constitutive sumoylation and DNA end processing...
July 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28732762/effect-of-class-ii-hdac-inhibition-on-glutamate-transporter-expression-and-survival-in-sod1-als-mice
#12
Andrea Lapucci, Leonardo Cavone, Daniela Buonvicino, Roberta Felici, Elisabetta Gerace, Clemens Zwergel, Sergio Valente, Antonello Mai, Alberto Chiarugi
Transcriptional deregulation emerges as a key pathogenetic mechanism in ALS pathogenesis, and non-class-specific histone deacetylase (HDACs) inhibitors proved of therapeutic efficacy in preclinical models of ALS. When tested in patients, however, these drugs failed, probably because of a lack of selectivity toward pathogenetic HDACs. Here, we studied the effects of MC1568, an inhibitor of Class-II HDACs which have been reported to contribute to ALS pathogenesis. We focused on transcriptional regulation of glutamate transporter EAAT2, whose reduced expression may contribute to motor neuron degeneration in ALS...
July 19, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28726589/proteomic-study-of-sumoylation-during-solanum-tuberosum-phytophthora-infestans-in-compatible-interactions
#13
Bertrand Colignon, Marc Dieu, Catherine Demazy, Edouard Delaive, Yordan Muhovski, Martine Raes, Sergio Mauro
Invasive plant pathogens have developed the ability to modify the metabolism of their host, promoting metabolic processes which facilitate the growth of the pathogen; at the general expense of the host. The particular enzymatic process SUMOylation which performs post-translational modification of target proteins, leading to changes in many aspects of protein activity and hence metabolism has been demonstrated to be active in many eukaryotic organisms, both animals and plants. Here we provide experimental evidence which indicates that in leaves of Solanum tuberosum which have been infected by Phytophthora infestans, the SUMO pathway enzymes of the host are partially under transcriptional control exerted by the oomycete...
July 20, 2017: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/28724604/a-simple-toolset-to-identify-endogenous-post-translational-modifications-for-a-target-protein-a-snapshot-of-the-egfr-signaling-pathway
#14
Henrick Horita, Andy Law, Soonjin Hong, Kim Middleton
Identification of a novel post-translational modification (PTM) for a target protein, defining its physiologic role, and studying its potential crosstalk with other PTMs is a challenging process. A set of highly sensitive tools termed Signal-Seeker kits was developed, which enables rapid and simple detection of post-translational modifications on any target protein.  The methodology for these tools utilizes affinity purification of modified proteins from a cell or tissue lysate and immunoblot analysis. These tools utilize a single lysis system that is effective at identifying endogenous, dynamic PTM changes, as well as the potential crosstalk between PTMs...
July 19, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28720507/formation-and-degradation-of-nitrogen-mustard-induced-mgmt-dna-crosslinking-in-16hbe-cells
#15
Jin Cheng, Feng Ye, Guorong Dan, Yuanpeng Zhao, Jiqing Zhao, Zhongmin Zou
N-methyl-2,2-di(chloroethyl)amine (HN2) is a kind of bifunctional alkyltating agent, which can react with nucleophilic groups in DNA and/or protein to form HN2-bridged crosslinking of target molecules, such as DNA-protein crosslinkings (DPC). O(6)-methylguanine-DNA methyltransferase (MGMT) is a DNA damage repair enzyme which solely repairs alkyl adduct on DNA directly. However, MGMT was detected to act as a protein cross-linked with DNA via alkylation in presence of HN2, and unexpectedly turned into a DNA damage enhancer in the form of MGMT-DNA cross-link (mDPC)...
July 15, 2017: Toxicology
https://www.readbyqxmd.com/read/28711876/nup153-orchestrates-sumoylation-for-dna-repair
#16
(no author information available yet)
No abstract text is available yet for this article.
July 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28705221/viral-manipulation-of-the-cellular-sumoylation-machinery
#17
REVIEW
Angela J Lowrey, Wyatt Cramblet, Gretchen L Bentz
Viruses exploit various cellular processes for their own benefit, including counteracting anti-viral responses and regulating viral replication and propagation. In the past 20 years, protein sumoylation has emerged as an important post-translational modification that is manipulated by viruses to modulate anti-viral responses, viral replication, and viral pathogenesis. The process of sumoylation is a multi-step cascade where a small ubiquitin-like modifier (SUMO) is covalently attached to a conserved ΨKxD/E motif within a target protein, altering the function of the modified protein...
July 14, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28695742/the-human-regulatory-protein-ki-1-57-is-a-target-of-sumoylation-and-affects-pml-nuclear-body-formation
#18
Ângela Saito, Edmarcia E de Souza, Fernanda C Costa, Gabriela V Meirelles, Kaliandra de Almeida Gonçalves, Marcos T Santos, Gustavo C Bressan, Mark E McComb, Catherine E Costello, Stephen A Whelan, Jörg Kobarg
Ki-1/57 is a nuclear and cytoplasmic regulatory protein first identified in malignant cells from Hodgkin's lymphoma. It is involved in gene expression regulation on both transcriptional and mRNA metabolism levels. Ki-1/57 belongs to the family of intrinsically unstructured proteins, undergoes phosphorylation by PKC and methylation by PRMT1. Previous characterization of its protein interaction profile by yeast two-hybrid screening showed that Ki- 1/57 interacts with proteins of the SUMOylation machinery: the SUMO E2 conjugating enzyme UBC9 and the SUMO E3 ligase PIAS3, which suggested that Ki-1/57 could be involved with this process...
July 11, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28692047/androgen-induces-g3bp2-and-sumo-mediated-p53-nuclear-export-in-prostate-cancer
#19
D Ashikari, K Takayama, T Tanaka, Y Suzuki, D Obinata, T Fujimura, T Urano, S Takahashi, S Inoue
The androgen receptor (AR) has a central role in prostate cancer progression, particularly treatment-resistance disease including castration-resistant prostate cancer. Loss of the p53 tumor suppressor, a nuclear transcription factor, is also known to contribute to prostate malignancy. Here we report that p53 is translocated to the cytoplasm by androgen-mediated induction of G3BP2, a newly described direct target gene of AR. G3BP2 induces both cell cycle progression and blocks apoptosis. Translocation of p53 is regulated by androgen-dependent sumoylation mediated by the G3BP2-interacting SUMO-E3 ligase, RanBP2...
July 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28680483/drosophila-cp190-and-dctcf-mediated-enhancer-blocking-is-augmented-by-sumoylation
#20
Theresa Jox, Melanie K Buxa, Dorte Bohla, Ikram Ullah, Igor Mačinković, Alexander Brehm, Marek Bartkuhn, Rainer Renkawitz
BACKGROUND: Chromatin insulators shield promoters and chromatin domains from neighboring enhancers or chromatin regions with opposing activities. Insulator-binding proteins and their cofactors mediate the boundary function. In general, covalent modification of proteins by the small ubiquitin-like modifier (SUMO) is an important mechanism to control the interaction of proteins within complexes. RESULTS: Here we addressed the impact of dSUMO in respect of insulator function, chromatin binding of insulator factors and formation of insulator speckles in Drosophila...
2017: Epigenetics & Chromatin
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