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https://www.readbyqxmd.com/read/28630282/desumoylation-of-gli1-by-senp1-attenuates-sonic-hedgehog-signaling
#1
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
#2
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/28576968/localisation-of-nup153-and-senp1-to-nuclear-pore-complexes-is-required-for-53bp1-mediated-dna-double-strand-break-repair
#3
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/28569748/the-critical-role-of-senp1-mediated-gata2-desumoylation-in-promoting-endothelial-activation-in-graft-arteriosclerosis
#4
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
#5
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
#6
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...
May 22, 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
#7
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
#8
(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
#9
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
#10
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
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
#11
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/27882949/sumo-specific-protease-1-protects-neurons-from-apoptotic-death-during-transient-brain-ischemia-reperfusion
#12
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/27852060/senp1-regulates-pten-stability-to-dictate-prostate-cancer-development
#13
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...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/27821551/senp1-drives-hypoxia-induced-polycythemia-via-gata1-and-bcl-xl-in-subjects-with-monge-s-disease
#14
Priti Azad, Huiwen W Zhao, Pedro J Cabrales, Roy Ronen, Dan Zhou, Orit Poulsen, Otto Appenzeller, Yu Hsin Hsiao, Vineet Bafna, Gabriel G Haddad
In this study, because excessive polycythemia is a predominant trait in some high-altitude dwellers (chronic mountain sickness [CMS] or Monge's disease) but not others living at the same altitude in the Andes, we took advantage of this human experiment of nature and used a combination of induced pluripotent stem cell technology, genomics, and molecular biology in this unique population to understand the molecular basis for hypoxia-induced excessive polycythemia. As compared with sea-level controls and non-CMS subjects who responded to hypoxia by increasing their RBCs modestly or not at all, respectively, CMS cells increased theirs remarkably (up to 60-fold)...
November 14, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27741516/senp1-promotes-proliferation-of-clear-cell-renal-cell-carcinoma-through-activation-of-glycolysis
#15
Baijun Dong, Yujing Gao, Xunlei Kang, Hongchang Gao, Jin Zhang, Hua Guo, Mingjian J You, Wei Xue, Jinke Cheng, Yiran Huang
Metabolic shift toward aerobic glycolysis is a fundamental element contributing to the development and progression of clear cell renal cell carcinoma (ccRCC). We and others previously observed enhanced glycolysis and diminished tricarboxylic acid (TCA) cycle activity in ccRCC tissue. Here, by integrated gene expression and metabolomic analyses of 36 matched pairs of tumor and adjacent normal tissues, we showed that expression of Sentrin/SUMO-specific protease 1 (SENP1) is positively associated with glycolysis levels in ccRCC...
December 6, 2016: Oncotarget
https://www.readbyqxmd.com/read/27703003/sumo-modification-reverses-inhibitory-effects-of-smad-nuclear-interacting-protein-1-in-tgf-%C3%AE-responses
#16
Sisi Liu, Jianyin Long, Bo Yuan, Mingjie Zheng, Mu Xiao, Jianming Xu, Xia Lin, Xin-Hua Feng
SNIP1 (Smad nuclear interacting protein 1) is a transcription repressor for the TGF-β and NF-κB signaling pathways through disrupting the recruitment of co-activator p300. However, it is unclear how the functions of SNIP1 in the TGF-β signaling pathway are controlled. Our present studies show that SNIP1 is covalently modified by small ubiquitin-like modifier (SUMO) in vitro and in vivo at three lysine sites: Lys(5), Lys(30), and Lys(108), with Lys(30) being the major SUMO modification site. SUMOylation of SNIP1 is enhanced by SUMO E3 ligase PIAS proteins and inhibited by SUMO proteases SENP1/2...
November 18, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27702761/senp1-regulates-ifn-%C3%AE-stat1-signaling-through-stat3-socs3-negative-feedback-loop
#17
Tingting Yu, Yong Zuo, Rong Cai, Xian Huang, Shuai Wu, Chenxi Zhang, Y Eugene Chin, Dongdong Li, Zhenning Zhang, Nansong Xia, Qi Wang, Hao Shen, Xuebiao Yao, Zhong-Yin Zhang, Song Xue, Lei Shen, Jinke Cheng
Interferon-γ (IFN-γ) triggers macrophage for inflammation response by activating the intracellular JAK-STAT1 signaling. Suppressor of cytokine signaling 1 (SOCS1) and protein tyrosine phosphatases can negatively modulate IFN-γ signaling. Here, we identify a novel negative feedback loop mediated by STAT3-SOCS3, which is tightly controlled by SENP1 via de-SUMOylation of protein tyrosine phosphatase 1B (PTP1B), in IFN-γ signaling. SENP1-deficient macrophages show defects in IFN-γ signaling and M1 macrophage activation...
April 1, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27693211/inhibition-of-sumo-specific-protease-1-induces-apoptosis-of-astroglioma-cells-by-regulating-nf-%C3%AE%C2%BAb-akt-pathways
#18
Wenrong Xia, Hongwei Tian, Xin Cai, HaiBo Kong, Wenliang Fu, Weiwei Xing, Yuanyuan Wang, Minji Zou, Yuhua Hu, Donggang Xu
SUMO-specific protease 1 (SENP1) is an important regulation protease in the protein desumoylation, which was shown to have a prooncogenicrole in many types of cancer. However, the mechanism of action for SENP1 in astrocytoma is not yet clear. Astrocytoma is the most frequent one among various neurogliomas, of which a subtype known as glioblastoma multiforme (GBM) is the most malignant brain glioma and seriously influences the life quality of the patients. In this study, the expression of SENP1 was detected in 28 cases of various grades of astrocytoma and 6 cases of normal human tissues...
December 31, 2016: Gene
https://www.readbyqxmd.com/read/27659494/senp1-is-a-crucial-regulator-for-cell-senescence-through-desumoylation-of-bmi1
#19
Nansong Xia, Juan Cai, Feifei Wang, Baijun Dong, Song Liu, Fengling Chen, Jinke Cheng, Yong Zuo
Cell senescence can limit proliferative potential and prevent tumorigenesis. Bmi1 is a key regulator in cell senescence by suppressing the Ink4a/Arf locus. However, how to regulate Bmi1 activity in cell senescence is largely unknown. Here, we show that SENP1 plays an important role in cell senescence by regulating Bmi1 SUMOylation. Senp1(-/-) primary MEF cells show resistance to cell senescence induced by passaging or other senescence inducing signals. SENP1 deficiency also reduces oncogene H-Ras(V12)-induced senescence, and enhances H-Ras(V12)-induced cell transformation...
September 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27644314/senp2-expression-was-induced-by-chronic-glucose-stimulation-in-ins1-cells-and-it-was-required-for-the-associated-induction-of-ccnd1-and-mafa
#20
Hye Seung Jung, Yu Mi Kang, Ho Seon Park, Byung Yong Ahn, Hakmo Lee, Min Joo Kim, Jin Young Jang, Sun-Whe Kim
Post-translational modification by bonding of small ubiquitin-like modifier (SUMO) peptides influences various cellular functions, and is regulated by SUMO-specific proteases (SENPs). Several proteins have been suggested to have diverse impact on insulin synthesis and secretion through SUMO modification in β cells. However, the role of SUMO modification in β cell mass has not been established. Here, we examined the changes in expression of Senp in INS1 cells and pancreatic islets under diabetes-relevant stress conditions and associated changes in β cell mass...
November 2016: Islets
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