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https://www.readbyqxmd.com/read/29128362/senp1-attenuates-the-liver-fibrosis-through-down-regulating-the-expression-of-smad2
#1
Lin-Shi Wu, Wei-Qing Qiu, Jian-Hua Sun, Jian Wang
To investigate whether SENP1 could play a regulating role in the liver fibrosis process, the Sprague-Dawley (SD) rats were used to establish the liver fibrosis rat models by intraperitoneally injecting with 1 ml/kg of 10% CCl4, while the control normal rats were injected with olive oil. Then confirmation experiments to verify the successful establishment of these models were conducted by detecting the cellular and lobular architecture, and liver function indexes using hematoxylin-eosin staining, Masson's trichrome staining and microplate method, respectively...
November 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29029226/new-insights-into-the-genetic-basis-of-monge-s-disease-and-adaptation-to-high-altitude
#2
Tsering Stobdan, Ali Akbari, Priti Azad, Dan Zhou, Orit Poulsen, Otto Appenzeller, Gustavo F Gonzales, Amalio Telenti, Emily H M Wong, Shubham Saini, Ewen F Kirkness, J Craig Venter, Vineet Bafna, Gabriel G Haddad
Human high-altitude (HA) adaptation or mal-adaptation is explored to understand the physiology, pathophysiology and molecular mechanisms that underlie long-term exposure to hypoxia. Here we report the results of an analysis of the largest whole-genome-sequencing of Chronic Mountain Sickness (CMS) and non-CMS individuals, identified candidate genes and functionally validated these candidates in a genetic model system (Drosophila). We used PreCIOSS algorithm that uses Haplotype Allele Frequency score to separate haplotypes carrying the favored allele from the non-carriers and accordingly prioritize genes associated with the CMS or non-CMS phenotype...
September 19, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28951950/high-altitude-adaptation-in-humans-from-genomics-to-integrative-physiology
#3
REVIEW
Priti Azad, Tsering Stobdan, Dan Zhou, Iain Hartley, Ali Akbari, Vineet Bafna, Gabriel G Haddad
About 1.2 to 33% of high-altitude populations suffer from Monge's disease or chronic mountain sickness (CMS). Number of factors such as age, sex, and population of origin (older, male, Andean) contribute to the percentage reported from a variety of samples. It is estimated that there are around 83 million people who live at altitudes > 2500 m worldwide and are at risk for CMS. In this review, we focus on a human "experiment in nature" in various high-altitude locations in the world-namely, Andean, Tibetan, and Ethiopian populations that have lived under chronic hypoxia conditions for thousands of years...
September 26, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28947497/gain-of-function-mutant-p53-activates-small-gtpase-rac1-through-sumoylation-to-promote-tumor-progression
#4
Xuetian Yue, Cen Zhang, Yuhan Zhao, Juan Liu, Alan W Lin, Victor M Tan, Justin M Drake, Lianxin Liu, Michael N Boateng, Jun Li, Zhaohui Feng, Wenwei Hu
Tumor suppressor p53 is frequently mutated in human cancer. Mutant p53 often promotes tumor progression through gain-of-function (GOF) mechanisms. However, the mechanisms underlying mutant p53 GOF are not well understood. In this study, we found that mutant p53 activates small GTPase Rac1 as a critical mechanism for mutant p53 GOF to promote tumor progression. Mechanistically, mutant p53 interacts with Rac1 and inhibits its interaction with SUMO-specific protease 1 (SENP1), which in turn inhibits SENP1-mediated de-SUMOylation of Rac1 to activate Rac1...
August 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28938454/11%C3%AE-hsd2-sumoylation-modulates-cortisol-induced-mineralocorticoid-receptor-nuclear-translocation-independently-of-effects-on-transactivation
#5
Rubén Jiménez-Canino, Fabián Lorenzo-Díaz, Alex Odermatt, Matthew A Bailey, Dawn E W Livingstone, Frederic Jaisser, Nicolette Farman, Diego Alvarez de la Rosa
The enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) has an essential role in aldosterone target tissues, conferring aldosterone selectivity for the mineralocorticoid receptor (MR) by converting 11β-hydroxyglucocorticoids to inactive 11-ketosteroids. Congenital deficiency of 11β-HSD2 causes a form of salt-sensitive hypertension known as the syndrome of apparent mineralocorticoid excess. The disease phenotype, which ranges from mild to severe, correlates well with reduction in enzyme activity. Furthermore, polymorphisms in the 11β-HSD2 coding gene (HSD11B2) have been linked to high blood pressure and salt sensitivity, major cardiovascular risk factors...
November 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28884683/characterisation-of-the-biflavonoid-hinokiflavone-as-a-pre-mrna-splicing-modulator-that-inhibits-senp
#6
Andrea Pawellek, Ursula Ryder, Triin Tammsalu, Lewis J King, Helmi Kreinin, Tony Ly, Ronald T Hay, Richard C Hartley, Angus I Lamond
We have identified the plant biflavonoid hinokiflavone as an inhibitor of splicing in vitro and modulator of alternative splicing in cells. Chemical synthesis confirms hinokiflavone is the active molecule. Hinokiflavone inhibits splicing in vitro by blocking spliceosome assembly, preventing formation of the B complex. Cells treated with hinokiflavone show altered subnuclear organization specifically of splicing factors required for A complex formation, which relocalize together with SUMO1 and SUMO2 into enlarged nuclear speckles containing polyadenylated RNA...
September 8, 2017: ELife
https://www.readbyqxmd.com/read/28796315/senp1-hif-1%C3%AE-feedback-loop-modulates-hypoxia-induced-cell-proliferation-invasion-and-emt-in-human-osteosarcoma-cells
#7
Xiaowei Wang, Xiaoju Liang, Huan Liang, Bing Wang
Hypoxia is an element intrinsic to most solid-tumor microenvironments, including that of osteosarcoma (OS), and is associated with resistance to therapy, poor survival, and a malignant phenotype. The purpose of the present study was to investigate the role and underlying mechanism of SUMO-specific protease 1 (SENP1)/hypoxia-inducible factor-1α (HIF-1α) feedback loop in hypoxic microenvironment of OS. We observed that the expression of SENP1 was remarkably upregulated in OS cells. Additionally, there was a concomitant high expression of HIF-1α and SENP1 in MG-63 cells under a hypoxic microenvironment...
August 10, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28770041/stromal-senp1-promotes-mouse-early-folliculogenesis-by-regulating-bmp4-expression
#8
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
#9
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 (neurogenic locus notch homolog protein) signaling pathway functions as a key cell-cell interaction mechanism controlling cell fate and tissue patterning, whereas 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 its signal transduction. Our previous study indicated the potential role of post-translational SUMO (small ubiquitin-like modifier) modification (SUMOylation) in vascular disorders...
September 1, 2017: Circulation Research
https://www.readbyqxmd.com/read/28748780/mir-133a-3p-targets-sumo-specific-protease-1-to-inhibit-cell-proliferation-and-cell-cycle-progress-in-colorectal-cancer
#10
Guo-Qiang Zhou, Fu Han, Zhi-Liang Shi, Liang Yu, Xue-Feng Li, Cheng Yu, Cheng-Long Shen, Dai-Wei Wan, Xin-Quo Zhu, Rui Li, Song-Bing He
Dysregulation of SUMO-specific protease 1(SENP1) expression has been reported in several kinds of cancer, including human colorectal and prostate cancers, proposing SENP1 as a oncogene with a critical role in cancer progression. MiR-133a-3p has been reported as a tumor suppressor in several malignant neoplasias. However, the precise molecular mechanisms underlying its role in colorectal cancer remain largely unknown. The aim of this work is to investigate the relationship between miR-133a-3p and SENP1 in colorectal cancer cells...
July 26, 2017: Oncology Research
https://www.readbyqxmd.com/read/28630282/desumoylation-of-gli1-by-senp1-attenuates-sonic-hedgehog-signaling
#11
Huaize Liu, Sen Yan, Jie Ding, Ting-Ting Yu, Steven Y Cheng
The transcriptional output of the Sonic Hedgehog morphogenic pathway is orchestrated by three Krüppel family transcription factors, Gli1 to -3, which undergo extensive posttranslational modifications, including ubiquitination and SUMOylation. Here, we report that the sentrin-specific peptidase SENP1 is the specific deSUMOylation enzyme for Gli1. We show that SUMOylation stabilizes Gli1 by competing with ubiquitination at conserved lysine residues and that SUMOylated Gli1 is enriched in the nucleus, suggesting that SUMOylation is a nuclear localization signal for Gli1...
September 15, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28622293/sumo-triggered-ubiquitination-of-nr4a1-controls-macrophage-cell-death
#12
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...
September 2017: Cell Death and Differentiation
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
#13
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 (also known as TP53BP1), a mediator of the DNA damage response. Here, we provide evidence that loss of Nup153 compromises 53BP1 sumoylation, a 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...
July 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28569748/the-critical-role-of-senp1-mediated-gata2-desumoylation-in-promoting-endothelial-activation-in-graft-arteriosclerosis
#14
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/28550686/microrna-186-suppresses-cell-proliferation-and-metastasis-through-targeting-sentrin-specific-protease-1-in-renal-cell-carcinoma
#15
Dan Jiao, Man Wu, Lei Ji, Feng Liu, Yingying Liu
Recent evidence suggests that dysregulation of microRNAs are associated with the development of multiple malignancies.miR-186 has been reported as a critical cancer regulator in several types of cancers. However, its functional significance and molecular mechanism underlying renal cell carcinoma (RCC) remains unknown. In this study, our results showed that miR-186 expression was dramatically downregulated in RCC tissues and cell lines compared to that in adjacent normal tissues and cell lines. Overexpression of miR-186 significantly inhibited cell growth, colony formation, cell invasion, caused cell cycle arrest at G0/G1 phase, and induced cell apoptosis as detected by MTT, colony formation, Transwell assay, and flow cytometry assays in RCC cells...
May 21, 2017: Oncology Research
https://www.readbyqxmd.com/read/28510446/modularly-constructed-synthetic-granzyme-b-molecule-enables-interrogation-of-intracellular-proteases-for-targeted-cytotoxicity
#16
Patrick Ho, Christopher Ede, Yvonne Y Chen
Targeted therapies promise to increase the safety and efficacy of treatments against diseases ranging from cancer to viral infections. However, the vast majority of targeted therapeutics relies on the recognition of extracellular biomarkers, which are rarely restricted to diseased cells and are thus prone to severe and sometimes-fatal off-target toxicities. In contrast, intracellular antigens present a diverse yet underutilized repertoire of disease markers. Here, we report a protein-based therapeutic platform-termed Cytoplasmic Oncoprotein VErifier and Response Trigger (COVERT)-which enables the interrogation of intracellular proteases to trigger targeted cytotoxicity...
August 18, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28417919/sumo-specific-cysteine-protease-1-promotes-epithelial-mesenchymal-transition-of-prostate-cancer-cells-via-regulating-smad4-desumoylation
#17
Xiaoyan Zhang, Hao Wang, Hua Wang, Fengjun Xiao, Prem Seth, Weidong Xu, Qinghua Jia, Chutse Wu, Yuefeng Yang, Lisheng Wang
In advanced prostate cancer, small ubiquitin-like modifier (SUMO)-specific cysteine protease 1 (SENP1) is up-regulated. However, the role of SENP1 in regulating deSUMOylation of TGF-β/SMADs signaling is unknown. In this study, we developed a lentiviral vector, PLKO.1-shSENP1, to silence SENP1 in prostate cancer cells with high metastatic characteristics (PC3M). Likewise, we also created an adenovirus vector, Ad5/F11p-SENP1 to over-express SENP1 in prostate cancer cells with low metastatic potential (LNCaP)...
April 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28411196/correction-senp1-desumoylates-and-regulates-pin1-protein-activity-and-cellular-function
#18
(no author information available yet)
No abstract text is available yet for this article.
April 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28408385/senp1-activity-sustains-cancer-stem-cell-in-hypoxic-hcc
#19
Alice Conigliaro, Marco Tripodi, Maurizio Parola
No abstract text is available yet for this article.
April 13, 2017: Gut
https://www.readbyqxmd.com/read/28258134/senp1-promotes-hypoxia-induced-cancer-stemness-by-hif-1%C3%AE-desumoylation-and-senp1-hif-1%C3%AE-positive-feedback-loop
#20
Chun-Ping Cui, Carmen Chak-Lui Wong, Alan Ka-Lun Kai, Daniel Wai-Hung Ho, Eunice Yuen-Ting Lau, Yu-Man Tsui, Lo-Kong Chan, Tan-To Cheung, Kenneth Siu-Ho Chok, Albert C Y Chan, Regina Cheuk-Lam Lo, Joyce Man-Fong Lee, Terence Kin-Wah Lee, Irene Oi Lin Ng
OBJECTIVE: We investigated the effect and mechanism of hypoxic microenvironment and hypoxia-inducible factors (HIFs) on hepatocellular carcinoma (HCC) cancer stemness. DESIGN: HCC cancer stemness was analysed by self-renewal ability, chemoresistance, expression of stemness-related genes and cancer stem cell (CSC) marker-positive cell population. Specific small ubiquitin-like modifier (SUMO) proteases 1 (SENP1) mRNA level was examined with quantitative PCR in human paired HCCs...
March 3, 2017: Gut
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