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Mandar T Naik, Mooseok Kang, Chun-Chen Ho, Pei-Hsin Liao, Yung-Lin Hsieh, Nandita M Naik, Szu-Huan Wang, Iksoo Chang, Hsiu-Ming Shih, Tai-Huang Huang
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March 19, 2018: Scientific Reports
Julián Esteban Sáez, Cristian Arredondo, Carlos Rivera, María Estela Andrés
CoREST family of transcriptional corepressors regulates gene expression and cell fate determination during development. CoREST corepressors recruit with different affinity the histone demethylase LSD1 (KDM1A) and the deacetylases HDAC1/2 to repress with variable strength the expression of target genes. CoREST protein levels are differentially regulated during cell fate decisions and in mature tissues. However, regulatory mechanisms of CoREST corepressors at the protein level have not been studied. Here, we report that CoREST (CoREST1, RCOR1) and its homologs CoREST2 (RCOR2) and CoREST3 (RCOR3) interact with PIASγ, a SUMO-E3 ligase...
March 19, 2018: Biochemical Journal
Mohamed Ali Maroui, Ghizlane Maarifi, Francis P McManus, Frederic Lamoliatte, Pierre Thibault, Mounira K Chelbi-Alix
We report that interferon (IFN) a treatment at short and long periods increases the global cellular SUMOylation and requires the presence of the SUMO E3 ligase promyelocytic leukemia protein (PML), the organizer of PML nuclear bodies (NBs). Several PML isoforms (PMLI-PMLVII) derived from a single PML gene by alternative splicing, share the same N-terminal region but differ in their C-terminal sequences. Introducing each of the human PML isoform in PML-negative cells revealed that enhanced SUMOylation in response to IFN is orchestrated by PMLIII and PMLIV...
March 13, 2018: Molecular & Cellular Proteomics: MCP
Xiaowei Hu, Lijing Zhang, Shuzhen Nan, Xiumei Miao, Pengfang Yang, Guoqin Duan, Hua Fu
Artemisia sphaerocephala, a dicotyledonous perennial semi-shrub belonging to the Artemisia genus of the Compositae family, is widely distributed in northwestern China. This shrub is one of the most important pioneer plants which is capable of protecting rangelands from wind erosion. It therefore plays a vital role in maintaining desert ecosystem stability. In addition, to its use as a forage grass, it has excellent prospective applications as a source of plant oil and as a plant-based fuel. The use of internal genes is the basis for accurately assessing Real time quantitative PCR...
March 2, 2018: Gene
Hayeon Baik, Mathias Boulanger, Moshen Hosseini, Julie Kowalczyk, Sonia Zaghdoudi, Tamara Salem, Jean Emmanuel Sarry, Yosr Hicheri, Guillaume Cartron, Marc Piechaczyk, Guillaume Bossis
Differentiation therapies using all-trans retinoic acid (ATRA) are highly efficient at treating acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia (AML). However, their efficacy, if any, is limited in the case of non-APL AML. We report here that inhibition of SUMOylation, a post-translational modification related to ubiquitination, restores the pro-differentiation and anti-proliferative activities of retinoids in non-APL AML. Controlled inhibition of SUMOylation with pharmacological inhibitors 2-D08 or anacardic acid, or via overexpression of SENP deSUMOylases, enhanced the ATRA-induced expression of key genes involved in differentiation, proliferation, and apoptosis in non-APL AML cells...
February 27, 2018: Cancer Research
Jörn Karhausen, Joshua D Bernstock, Kory R Johnson, Huaxin Sheng, Qing Ma, Yuntian Shen, Wei Yang, John M Hallenbeck, Wulf Paschen
The intestinal epithelium constitutes a crucial defense to the potentially life-threatening effects of gut microbiota. However, due to a complex underlying vasculature, hypoperfusion and resultant tissue ischemia pose a particular risk to function and integrity of the epithelium. The small ubiquitin-like modifier (SUMO) conjugation pathway critically regulates adaptive responses to metabolic stress and is of particular significance in the gut, as inducible knockout of the SUMO-conjugating enzyme Ubc9 results in rapid intestinal epithelial disintegration...
February 22, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Wan-Shan Yang, Mel Campbell, Hsing-Jien Kung, Pei-Ching Chang
Small ubiquitin-like modifier (SUMO) modification is an important post-translational modification (PTM) that mediates signal transduction primarily through modulating protein-protein interactions. Similar to ubiquitin modification, SUMOylation is directed by a sequential enzyme cascade including E1-activating enzyme (SAE1/SAE2), E2-conjugation enzyme (Ubc9), and E3-ligase (i.e., PIAS family, RanBP2, and Pc2). However, different from ubiquitination, an E3 ligase is non-essential for the reaction but does provide precision and efficacy for SUMO conjugation...
January 29, 2018: Journal of Visualized Experiments: JoVE
Maria Lauda Tomasi, Komal Ramani, Minjung Ryoo, Carla Cossu, Andrea Floris, Ben J Murray, Ainhoa Iglesias-Ara, Ylenia Spissu, Nirmala Mavila
Alcohol acts through numerous pathways leading to alcoholic liver disease (ALD). Cytochrome P450 (CYP2E1), an ethanol-inducible enzyme, metabolizes ethanol-producing toxic reactive oxygen species (ROS) and is regulated at the posttranslational level. Small ubiquitin-like modifier (SUMO)ylation is a posttranslational modification that involves the addition of SUMOs, which modulate protein stability, activity, and localization. We demonstrated that ubiquitin-conjugation enzyme 9, the SUMO-conjugating enzyme, is induced in the livers of an intragastric ethanol mouse model...
January 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
E Ficulle, M D Shah Sufian, C Tinelli, M Corbo, M Feligioni
Protein activities and mechanisms related to aging has become a growing interest nowadays. Since SUMOylation is implicated in several cellular processes, its investigation related to senescence, aging and frailty is of high interest. In our study, wild type mice cortical lysates, synaptosomes and plasma have been processed to evaluate SUMOylation and SUMO machinery expression (Ubc9 and SENP1 enzymes) profile at different ages. In cortical lysates, SUMO-1ylation reached a peak at 6 months followed by a decrease; while in synaptosomes, it progressively increased till 18 months...
January 8, 2018: Neuroscience Letters
Xiaoyu He, Qiaohong Lai, Cai Chen, Na Li, Fei Sun, Wenting Huang, Shu Zhang, Qilin Yu, Ping Yang, Fei Xiong, Zhishui Chen, Quan Gong, Boxu Ren, Jianping Weng, Décio L Eizirik, Zhiguang Zhou, Cong-Yi Wang
AIMS/HYPOTHESIS: Post-translational attachment of a small ubiquitin-like modifier (SUMO) to the lysine (K) residue(s) of target proteins (SUMOylation) is an evolutionary conserved regulatory mechanism. This modification has previously been demonstrated to be implicated in the control of a remarkably versatile regulatory mechanism of cellular processes. However, the exact regulatory role and biological actions of the E2 SUMO-conjugating enzyme (UBC9)-mediated SUMOylation function in pancreatic beta cells has remained elusive...
January 3, 2018: Diabetologia
L Yuan, Z M Jiang, X H Chen, X Y Bian, Y X Li, X F Ma, X Z Liu
Objective: To reduce the stemness maintenance ability of endometrial cancer stem cell and increase its sensitivity to chemotherapy by inducing hypoxia inducible factor 1α (HIF-1α) protein deSUMOylation. Methods: Lentiviral plasmid mediated ubiquitin carrier protein 9 (Ubc9) gene silencing was transgened into KLE endometrial carcinoma cells. The expression of Ubc9, small ubiquitin-related modifier 1(SUMO1) and HIF-1α protein was detected by Western blotting. Then tumor stem cells clones were cultured in 96 well plates, and these clone balls diameter were calculated...
December 5, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Cong Wang, Nanfang Zeng, Siyu Liu, Qi Miao, Lei Zhou, Xinna Ge, Jun Han, Xin Guo, Hanchun Yang
SUMOylation is a reversible post-translational modification that regulates the function of target protein. In this study, we first predicted by software that the multiple proteins of porcine reproductive and respiratory syndrome virus (PRRSV) could be sumoylated. Next, we confirmed that Nsp1β, Nsp4, Nsp9, Nsp10 and nucleocapsid (N) protein of PRRSV could interact with the sole SUMO E2 conjugating enzyme Ubc9, and Ubc9 could be co-localized with Nsp1β, Nsp4, Nsp9 and Nsp10 in the cytoplasm, while with N protein in both the cytoplasm and nucleus...
2017: PloS One
Mandar T Naik, Mooseok Kang, Chun-Chen Ho, Pei-Hsin Liao, Yung-Lin Hsieh, Nandita M Naik, Szu-Huan Wang, Iksoo Chang, Hsiu-Ming Shih, Tai-Huang Huang
The negatively charged amino acid-dependent sumoylation motif (NDSM) carries an additional stretch of acidic residues downstream of the consensus Ψ-K-x-E/D sumoylation motif. We have previously shown that acetylation of the SUMO E2 conjugase enzyme, Ubc9, at K65 downregulates its binding to the NDSM and renders a selective decrease in sumoylation of substrates with the NDSM motif. Here, we provide detailed structural, thermodynamic, and kinetics results of the interactions between Ubc9 and its K65 acetylated variant (Ac-Ubc9K65 ) with three NDSMs derived from Elk1, CBP, and Calpain2 to rationalize the mechanism beneath this reduced binding...
December 12, 2017: Scientific Reports
Ramesh Kumar, Román González-Prieto, Zhenyu Xiao, Matty Verlaan-de Vries, Alfred C O Vertegaal
SUMO-targeted ubiquitin ligases (STUbLs) mediate the ubiquitylation of SUMOylated proteins to modulate their functions. In search of direct targets for the STUbL RNF4, we have developed TULIP (targets for ubiquitin ligases identified by proteomics) to covalently trap targets for ubiquitin E3 ligases. TULIP methodology could be widely employed to delineate E3 substrate wiring. Here we report that the single SUMO E2 Ubc9 and the SUMO E3 ligases PIAS1, PIAS2, PIAS3, ZNF451, and NSMCE2 are direct RNF4 targets. We confirm PIAS1 as a key RNF4 substrate...
November 27, 2017: Nature Communications
Donghua Wen, Jianguo Wu, Lei Wang, Zheng Fu
As a pivotal mitotic regulator, polo-like kinase 1 (PLK1) is under highly coordinated and multi-layered regulation. However, the pathways that control PLK1's activity and function have just begun to be elucidated. PLK1 has recently been shown to be functionally modulated by post-translational modifications (PTMs), including phosphorylation and ubiquitination. Herein, we report that SUMOylation plays an essential role in regulating PLK1's mitotic function. We found that Ubc9 was recruited to PLK1 upon initial phosphorylation and activation by CDK1/cyclin B...
November 21, 2017: Cell Reports
F Sheng, Y M Shen, Q H Wan, Y X Li, X F Ma, Z M Jiang, D Y Zhang, X Z Liu, W H Wu
Objective: To investigate the effect of AKT1 deSUMOylation induced by Ubc9 silencing on the proliferation and metastasis of hepatocellular carcinoma (HCC) cells. Methods: The Ubc9 gene was silenced using RNA interference, and the expression levels of Ubc9, SUMO1 and AKT1 protein were detected by Western blot. Cell proliferation and cell cycle was analyzed by MTT and flow cytometry. Wound healing and transwell assays were used to detect the cell migration ability. Furthermore, the xenograft model was established, and tumor growth curves were drawn...
November 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
Jiaoli Hu, Pengcheng Xue, Xinbang Mao, Lin Xie, Guodong Li, Zhipeng You
Diabetic retinopathy (DR) is an increasing global health concern that causes vision loss and blindness. Reactive oxygen species (ROS) are considered to be a principal cause of DR. An important source of ROS is the oxidization of NADPH. In the present study, NADPH oxidase 1 (Nox1)‑expressing human retinal epithelial cell (HREC) lines were generated and infected with small ubiquitin‑like modifier 1 (SUMO1) and/or ubiquitin conjugating enzyme E2 I (UBC9) lentiviral pGMLV constructs. The viabilities, apoptotic capacities and ROS production levels of the HREC lines were quantified using Hoechst 33258, annexin V/propidium iodide and dichlorodihydrofluorescein diacetate assays, respectively...
January 2018: Molecular Medicine Reports
Zhiqing Li, Qixin Cui, Jian Xu, Daojun Cheng, Xiaoyan Wang, Bingqian Li, Jae Man Lee, Qingyou Xia, Takahiro Kusakabe, Ping Zhao
Polo-like kinase 1 (Plk1) is a crucial cell cycle regulator by its specific localization and activity during cell cycle. It has been shown that the phosphorylation and ubiquitylation of Plk1 are required for its own activation and localization. Here, we report that SUMOylation regulates the activity of Plk1 in the lepidopteran insect of Bombyx mori. In the absence of SUMOylation, it causes the lost localization of Plk1 on centrosomes and kinetochores, as well as an uneven distribution in midzone. We further identify that the putative SUMOylation site of Bombyx Plk1 at lysine 466 is required for its localization on centrosomes, and K466 mutation in Plk1 could influence its interaction with Smt3/Ubc9 complex...
November 14, 2017: Scientific Reports
Yiwei Xiong, Chengjin Ye, Naiqi Yang, Madanqi Li, Hebin Liu
Although the immune adaptor adhesion and degranulation-promoting adaptor protein (ADAP) acts as a key mediator of integrin inside-out signaling leading to T cell adhesion, the regulation of this adaptor during integrin activation and clustering remains unclear. We now identify Ubc9, the sole small ubiquitin-related modifier E2 conjugase, as an essential regulator of ADAP where it is required for TCR-induced membrane recruitment of the small GTPase Rap1 and its effector protein RapL and for activation of the small GTPase Rac1 in T cell adhesion...
December 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
Manish Thiruvalluvan, Paul G Barghouth, Assaf Tsur, Limor Broday, Néstor J Oviedo
Mechanisms underlying anteroposterior body axis differences during adult tissue maintenance and regeneration are poorly understood. Here, we identify that post-translational modifications through the SUMO (Small Ubiquitin-like Modifier) machinery are evolutionarily conserved in the Lophotrocozoan Schmidtea mediterranea. Disruption of SUMOylation in adult animals by RNA-interference of the only SUMO E2 conjugating enzyme Ubc9 leads to a systemic increase in DNA damage and a remarkable regional defect characterized by increased cell death and loss of the posterior half of the body...
November 2, 2017: Cellular and Molecular Life Sciences: CMLS
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