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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
Ijeoma Uzoma, Jianfei Hu, Eric Cox, Shuli Xia, Jianying Zhou, Hee-Sool Rho, Catherine Guzzo, Corry Paul, Olutobi Ajala, C Rory Goodwin, Junseop Jeong, Cedric Moore, Hui Zhang, Pamela Meluh, Seth Blackshaw, Michael Matunis, Jiang Qian, Heng Zhu
Proteomics studies have revealed that SUMOylation is widely used posttranslational modification (PTM) in eukaryotes. However, how SUMO E1/2/3 complexes use different SUMO isoforms and recognize substrates remains largely unknown.  Using a human proteome microarray-based activity screen, we identified over 2,500 proteins that undergo SUMO E3-dependent SUMOylation.  We next constructed a SUMO isoform- and E3 ligase-dependent enzyme-substrate relationship network. Protein kinases were significantly enriched among SUMOylation substrates, suggesting crosstalk between tyrosine phosphorylation and SUMOylation...
February 8, 2018: Molecular & Cellular Proteomics: MCP
Bo Wei, Chao Huang, Bin Liu, Yang Wang, Nansong Xia, Qiuju Fan, Guo-Qiang Chen, Jinke Cheng
Progression of mitotic cell cycle as well as chromosome condensation and segregation are controlled by posttranslational protein modifications such as phosphorylation and SUMOylation. However, how SUMO isopeptidases (SENP) regulate cell mitotic procession is largely unknown. Here we demonstrate that precise phosphorylation of SENP3 during mitosis suppresses SENP3 de-SUMOylation activity towards chromosome-associated proteins including Topoisomerase IIα (Topo IIα). Cyclin B-dependent kinases 1 (CDK1) and protein phosphatase 1α (PP1α) were identified as the kinase and phosphatase in control of mitotic SENP3 phosphorylation, respectively...
February 8, 2018: Cancer Research
Cyril Addi, Jian Bai, Arnaud Echard
Cytokinesis is the process by which a mother cell is physically cleaved into two daughter cells. In animal cells, cytokinesis begins with the contraction of a plasma membrane-associated actomyosin ring that is responsible for the ingression of a cleavage furrow. However, the post-furrowing steps of cytokinesis are less understood. Here, we highlight key recent findings that reveal a profound remodeling of several classes of cytoskeletal elements and cytoplasmic filaments (septins, microtubules, actin and ESCRT) in the late steps of cytokinesis...
February 10, 2018: Current Opinion in Cell Biology
Chen-Xing Ji, Yang-Hua Fan, Fan Xu, Shi-Gang Lv, Min-Hua Ye, Miao-Jing Wu, Xin-Gen Zhu, Lei Wu
Derived from brain glial cells, gliomas are currently the most common primary tumours in the central nervous system and are characterised by a high recurrence rate and poor prognosis. RWDD3 (RWD domain-containing sumoylation enhancer, also termed RSUME), which can be induced by cellular stress, such as CoCl2, heat shock and hypoxia, may play a crucial role in tumour angiogenesis, growth and metastasis. MicroRNAs (miRNAs) have been demonstrated to act as negative regulators of post-transcriptional gene expression and are involved in tumour growth and metastasis...
February 13, 2018: Oncology Reports
Byeong Hyeok Choi, Changyan Chen, Mark Philips, Wei Dai
RAS proteins are GTPases that participate in multiple signal cascades, regulating crucial cellular processes including cell survival, proliferation, differentiation, and autophagy. Mutations or deregulated activities of RAS are frequently the driving force for oncogenic transformation and tumorigenesis. Given the important roles of the small ubiquitin-related modifier (SUMO) pathway in controlling the stability, activity, or subcellular localization of key cellular regulators, we investigated here whether RAS proteins are posttranslationally modified (i...
January 12, 2018: Oncotarget
Kentaro Ohkuni, Reuben Levy-Myers, Jack Warren, Wei-Chun Au, Yoshimitsu Takahashi, Richard E Baker, Munira A Basrai
Stringent regulation of cellular levels of evolutionarily conserved centromeric histone H3 variant (CENP-A in humans, CID in flies, Cse4 in yeast) prevents its mislocalization to non-centromeric chromatin. Overexpression and mislocalization of CENP-A has been observed in cancers and leads to aneuploidy in yeast, flies, and human cells. Ubiquitin-mediated proteolysis of Cse4 by E3 ligases such as Psh1 and Sumo-Targeted Ubiquitin Ligase (STUbL) Slx5 prevent mislocalization of Cse4. Previously, we identified Siz1 and Siz2 as the major E3 ligases for sumoylation of Cse4...
February 5, 2018: G3: Genes—Genomes—Genetics
Emanuele Buratti
Nuclear factor TDP-43 is a ubiquitously expressed RNA binding protein that plays a key causative role in several neurodegenerative diseases, especially in the ALS/FTD spectrum. In addition, its aberrant aggregation and expression has been recently observed in other type of diseases, such as myopathies and Niemann-Pick C, a lysosomal storage disease. Areas Covered. This review aims to specifically cover the post-translational modifications (PTMs) that can affect TDP-43 function and cellular status both in health and disease...
February 10, 2018: Expert Opinion on Therapeutic Targets
Jifeng Zhang, Bo Zhao, Xiaonan Zhu, Jiong Li, Fengming Wu, Sumei Li, Xiaobing Gong, Caihui Cha, Guoqing Guo
The posttranslational modifications of CRMP2 play an important role in axon outgrowth, cell polarization and dendritic morphogenesis. However, whether CRMP2 and its posttranslational modifications are involved in dendritic spine development specifically is not completely clear. Here, we show that CRMP2 can promote the formation and maturation of dendritic spines in cultured hippocampal neurons. Overexpression of CRMP2 results in an increase in the density of spines especially the mushroom-shape spines. The amplitude and frequency of miniature excitatory postsynaptic currents (mEPSCs) are both enhanced and the intensity of PSD95 is strengthened in the neurons with CRMP2 overexpression...
February 6, 2018: Brain Research Bulletin
WanYing Lin, Jie Luo, Yin Sun, ChangYi Lin, Gonghui Li, Yuanjie Niu, Chawnshang Chang
Unlike the androgen-deprivation therapy (ADT) to either reduce the androgen biosynthesis (for example, Abiraterone) or to prevent binding of androgen to the androgen receptor (AR) (for example, Casodex or Enzalutamide), that may result in the decreasing the prostate cancer (PCa) cell growth yet may also increasing the PCa cell invasion, the recently identified AR degradation enhancer ASC-J9® may function via degrading the AR protein to simultaneously suppress the PCa cell proliferation and invasion. The details of this unique mechanism, however, remain unclear...
February 6, 2018: Cancer Letters
Yinping Du, Ping Liu, Tongda Xu, Defeng Pan, Hong Zhu, Nana Zhai, Yanbin Zhang, Dongye Li
BACKGROUND/AIMS: The myocardial sarcoplasmic reticulum calcium ATPase (SERCA2a) is a pivotal pump responsible for calcium cycling in cardiomyocytes. The present study investigated the effect of luteolin (Lut) on restoring SERCA2a protein level and stability reduced by myocardial ischemia/reperfusion (I/R) injury. We verified a hypothesis that Lut protected against myocardial I/R injury by regulating SERCA2a SUMOylation. METHODS: The hemodynamic data, myocardial infarct size of intact hearts, apoptotic analysis, mitochondrial membrane potential (ΔΨm), the level of SERCA2a SUMOylation, and the activity and expression of SERCA2a were examined in vivo and in vitro to clarify the cardioprotective effects of Lut after SUMO1 was knocked down or over-expressed...
February 2, 2018: Cellular Physiology and Biochemistry
Huadie Liu, Jianshuang Li, Di Lu, Jie Li, Minmin Liu, Yuanzheng He, Bart O Williams, Jiada Li, Tao Yang
Sumoylation is a post-translational modification process having an important influence in mesenchymal stem cell (MSC) differentiation. Thus, sumoylation-modulating chemicals might be used to control MSC differentiation for skeletal tissue engineering. In this work, we studied how the differentiation of mouse bone marrow stromal cells (mBMSCs) is affected by ginkgolic acid (GA), a potent sumoylation inhibitor also reported to inhibit histone acetylation transferase (HAT). Our results show that GA promoted the differentiation of mBMSCs into adipocytes when cultured in osteogenic medium...
February 7, 2018: Scientific Reports
Shweta Prasad, Pramod Kumar Pal
No abstract text is available yet for this article.
February 7, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
Andreia Lee, Oya CingÖz, Yosef Sabo, Stephen P Goff
Moloney Murine Leukemia Virus (M-MLV) proviral DNA is transcriptionally silenced in embryonic cells by a large repressor complex tethered to the provirus by two sequence-specific DNA binding proteins, ZFP809 and YY1. A central component of the complex is Trim28, a scaffold protein that regulates many target genes involved in cell cycle progression, DNA damage responses, and viral gene expression. The silencing activity of Trim28, and its interactions with corepressors are often regulated by post-translational modifications such as sumoylation and phosphorylation...
January 26, 2018: Virology
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
Eun Ju Lee, Injoo Hwang, Ji Yeon Lee, Jong Nam Park, Keun Cheon Kim, Gi-Hwan Kim, Chang-Mo Kang, Irene Kim, Seo-Yeon Lee, Hyo-Soo Kim
Human embryonic stem cell-derived mesenchymal stem cells (hE-MSCs) have greater proliferative capacity than other human mesenchymal stem cells (hMSCs), suggesting that they may have wider applications in regenerative cellular therapy. In this study, to uncover the anti-senescence mechanism in hE-MSCs, we compared hE-MSCs with adult bone marrow (hBM-MSCs) and found that hepatocyte growth factor (HGF) was more abundantly expressed in hE-MSCs than in hBM-MSCs and that it induced the transcription of RAD51 and facilitated its SUMOylation at K70...
December 19, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
Özge Karayel, Erdem Şanal, Sven H Giese, Zeynep Cansu Üretmen Kagıalı, Ayşe Nur Polat, Chi-Kuo Hu, Bernhard Y Renard, Nurcan Tuncbag, Nurhan Özlü
The successful completion of cytokinesis requires the coordinated activities of diverse cellular components including membranes, cytoskeletal elements and chromosomes that together form partly redundant pathways, depending on the cell type. The biochemical analysis of this process is challenging due to its dynamic and rapid nature. Here, we systematically compared monopolar and bipolar cytokinesis and demonstrated that monopolar cytokinesis is a good surrogate for cytokinesis and it is a well-suited system for global biochemical analysis in mammalian cells...
February 2, 2018: Scientific Reports
Yimeng Shen, Yanxia Li, Xiaofang Ma, Qiaohao Wan, Zhongmin Jiang, Yixin Liu, Dianying Zhang, Xiaozhi Liu, Wenhan Wu
Connexin 43 (Cx43) can be modified and regulated by small ubiquitin-like modifier (SUMO)1; however, its role in liver cancer stem cells is poorly understood. In this study, we found a significant difference in the expression of Cx43 and SUMO1 between cancer stem cells and non-cancer stem cells in liver cancer. In liver cancer stem cells, Cx43 was almost absent, although the level of SUMO1 was significantly higher than that in non-cancer stem cells. Further experiments confirmed that the conjugated site of Cx43 by SUMO1 was located in Lys-144 and Lys-237, both of which are highly conserved among species...
February 1, 2018: International Journal of Oncology
Ken-Ichi Takayama, Takashi Suzuki, Tomoaki Tanaka, Tetsuya Fujimura, Satoru Takahashi, Tomohiko Urano, Kazuhiro Ikeda, Satoshi Inoue
Prostate cancer growth is promoted by the gene regulatory action of androgen receptor (AR) and its downstream signals. The aberrant dysfunction of tumor suppressor p53 has an important role in the prognosis of cancer. We previously found that androgen treatments translocate p53 to the cytoplasm. The mechanism of this translocation depends on sumoylation of p53 by complex of SUMO E3 ligase RanBP2 with androgen-induced GTPase-activating protein-binding protein 2 (G3BP2). Here, we identified tripartite motif-containing protein 25 (TRIM25)/estrogen-responsive finger protein (Efp) as a novel interacting partner of G3BP2 protein complex...
January 30, 2018: Oncogene
Julien Sallais, Sruthi Alahari, Andrea Tagliaferro, Jayonta Bhattacharjee, Martin Post, Isabella Caniggia
Adaptations to changes in oxygen are critical to ensure proper placental development, and impairments in oxygen sensing mechanisms characterize placental pathologies such as preeclampsia. In this study, we examined the involvement of SUMOylation, a reversible posttranslational modification, in the regulation of the asparaginyl hydroxylase Factor Inhibiting Hypoxia Inducible Factor 1 (FIH1) in the human placenta in development and in disease status. FIH1 protein abundance and spatial distribution in the developing placenta directly correlated with oxygen tension in vivo...
December 26, 2017: Oncotarget
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