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Samah Matmati, Mélina Vaurs, José M Escandell, Laetitia Maestroni, Toru M Nakamura, Miguel G Ferreira, Vincent Géli, Stéphane Coulon
Mammalian CST (CTC1-STN1-TEN1) complex fulfills numerous functions including rescue of the stalled replication forks and termination of telomerase action. In fission yeast lacking the CTC1 ortholog, the Stn1-Ten1 complex restricts telomerase action via its sumoylation-mediated interaction with Tpz1TPP1 . We identify a small ubiquitin-like modifier (SUMO)-interacting motif (SIM) in the carboxyl-terminal part of Stn1 and show that this domain is crucial for SUMO and Tpz1-SUMO interactions. Point mutations in the SIM (Stn1-226) lead to telomere elongation, impair Stn1-Ten1 recruitment to telomeres, and enhance telomerase binding, revealing that Stn1 SIM domain contributes to the inhibition of telomerase activity at chromosome ends...
May 2018: Science Advances
Francis P McManus, Véronique Bourdeau, Mariana Acevedo, Stéphane Lopes-Paciencia, Lian Mignacca, Frédéric Lamoliatte, John W Rojas Pino, Gerardo Ferbeyre, Pierre Thibault
Several regulators of SUMOylation have been previously linked to senescence but most targets of this modification in senescent cells remain unidentified. Using a two-step purification of a modified SUMO3, we profiled the SUMO proteome of senescent cells in a site-specific manner. We identified 25 SUMO sites on 23 proteins that were significantly regulated during senescence. Of note, most of these proteins were PML nuclear body (PML-NB) associated, which correlates with the increased number and size of PML-NBs observed in senescent cells...
May 17, 2018: Scientific Reports
Monique Priscilla Catharina Mulder, Remco Merkx, Katharina Witting, Dharjath Hameed, Dris El Atmioui, Lindsey Lelieveld, Frauke Liebelt, Jacques Neefjes, Ilana Berlin, Alfred Vertegaal, Huib Ovaa
SUMO, a post-translational modifier critical for cell cycle progression and genome stability, plays a role in tumorigenesis rendering SUMO-specific enzymes as potential pharmacological targets. However, systematic generation of tools for activity profiling of SUMO-specific enzymes has proven challenging, leading us to develop a diversifiable synthetic platform for a SUMO toolbox using a direct linear synthesis protocol, permitting N- and C-terminal labeling strategies to incorporate dyes and reactive warheads, respectively...
May 17, 2018: Angewandte Chemie
Nathalia Varejão, Eva Ibars, Jara Lascorz, Neus Colomina, Jordi Torres-Rosell, David Reverter
Modification of chromosomal proteins by conjugation to SUMO is a key step to cope with DNA damage and to maintain the integrity of the genome. The recruitment of SUMO E3 ligases to chromatin may represent one layer of control on protein sumoylation. However, we currently do not understand how cells upregulate the activity of E3 ligases on chromatin. Here we show that the Nse2 SUMO E3 in the Smc5/6 complex, a critical player during recombinational DNA repair, is directly stimulated by binding to DNA Activation of sumoylation requires the electrostatic interaction between DNA and a positively charged patch in the ARM domain of Smc5, which acts as a DNA sensor that subsequently promotes a stimulatory activation of the E3 activity in Nse2...
May 16, 2018: EMBO Journal
Yue Zhu, Hong-Yan Lu, Xiao-Bo Hao, Ming Chang, Qiu-Xia Wang, Feng-Yun Wan, Xue-Qing Wan
OBJECTIVE: To study the expression of SUMO-modified CCAAT enhancer binding protein α (C/EBPα) in preterm rat model of bronchopulmonary dysplasisa (BPD) induced by hyperoxia exposure and its role. METHODS: Eighteen preterm rats were randomly divided into an air group and a hyperoxia group (n=9 each). The model of BPD was prepared in preterm rats exposed to hyperoxia. The rats from the two groups were sacrificed on postnatal days 4, 7 and 14 respectively (3 rats at each time) and lung tissues were harvested...
May 2018: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
Bin Chen, Jie Luo, Yirui Zhou, Xu Xin, Rong Cai, Chunhua Ling
GATA2 regulated transcriptional network has been validated requisite for RAS oncogene-driven non-small cell lung cancer (NSCLC). GATA2 has been reported as a SUMOylated protein. In endothelial cells, its transcriptional activity is attenuated by SUMO-2 conjugation, which is specifically catalyzed by its E3 ligase PIASy. In this study, we found a decreased expression of PIASy in RAS mutant NSCLC cell lines and specimens with RAS mutations. Forced expression of PIASy in NSCLC cells inhibits their viability in vitro , as well as tumorigenesis and growth in vivo ...
2018: Journal of Cancer
Yi Ding, Masako Kaido, Elena Llano, Alberto M Pendas, Tomoya S Kitajima
The production of haploid gametes requires the maintenance of centromeric cohesion between sister chromatids through the transition between two successive meiotic divisions, meiosis I and meiosis II. One mechanism for the cohesion maintenance is shugoshin-dependent protection of centromeric cohesin at anaphase I onset [1-3]. However, how centromeric cohesion is maintained during late anaphase I and telophase I, when centromeric shugoshin is undetectable [1-3], remains largely unexplored. Here we show that the centromeric small ubiquitin-related modifier (SUMO) pathway is critical for the maintenance of centromeric cohesion during post-anaphase-I periods in mouse oocytes...
May 3, 2018: Current Biology: CB
Hongjing Cheng, Xun Sun, Ji Li, Ping He, Wanqi Liu, Xiangwei Meng
Colorectal cancer is a serious threat to human health, and has a high mortality rate. There is currently no effective therapy for end-stage colorectal cancer. In recent years, molecular targeted therapy has received increasing attention for cancer treatment. In particular, the role of Uba2, a vital component of SUMO-activating enzyme, has been highlighted, which plays important roles in the progression of certain cancers; however, its role in colorectal cancer remains unclear. Accordingly, the aim of this study was to evaluate the relationship between Uba2 and colorectal cancer...
May 10, 2018: Journal of Cellular Biochemistry
Myoung Kyu Lee, Ye Ji Kim, Young-Eui Kim, Tae-Hee Han, Jens Milbradt, Manfred Marschall, Jin-Hyun Ahn
Interferon-stimulated gene (ISG) 15 encodes a ubiquitin-like protein that can be conjugated to proteins via an enzymatic cascade involving the E1, E2, and E3 enzymes. ISG15 expression and protein ISGylation modulate viral infection; however, the viral mechanisms regulating the function of ISG15 and ISGylation are not well understood. We recently showed that ISGylation suppresses the growth of human cytomegalovirus (HCMV) at multiple steps of the virus life cycle, and that the virus-encoded pUL26 protein inhibits protein ISGylation...
May 9, 2018: Journal of Virology
Jordan R Becker, David Gallo, Wendy Leung, Taylor Croissant, Yee Mon Thu, Hai Dang Nguyen, Timothy K Starr, Grant W Brown, Anja-Katrin Bielinsky
Overexpression of the flap endonuclease FEN1 has been observed in a variety of cancer types and is a marker for poor prognosis. To better understand the cellular consequences of FEN1 overexpression we utilized a model of its Saccharomyces cerevisiae homolog, RAD27. In this system, we discovered that flap endonuclease overexpression impedes replication fork progression and leads to an accumulation of cells in mid-S phase. This was accompanied by increased phosphorylation of the checkpoint kinase Rad53 and histone H2A-S129...
May 7, 2018: Nucleic Acids Research
Berta Pozzi, Pablo Mammi, Laureano Bragado, Luciana E Giono, Anabella Srebrow
Spliceosomal proteins have been revealed as SUMO conjugation targets. Moreover, we have reported that many of these are in a SUMO-conjugated form when bound to a pre-mRNA substrate during a splicing reaction. We demonstrated that SUMOylation of Prp3 (PRPF3), a component of the U4/U6 di-snRNP, is required for U4/U6•U5 tri-snRNP formation and/or recruitment to active spliceosomes. Expanding upon our previous results, we have shown that the splicing factor SRSF1 stimulates SUMO conjugation to several spliceosomal proteins...
May 9, 2018: RNA Biology
Wrenetha A Julion, Jen'nea Sumo, Dawn T Bounds
Many studies have examined factors influencing African-American (AA) participation in research studies. But none inform the recruitment of AA men into fatherhood intervention research. Our purpose is to describe the recruitment and enrollment framework of the Dedicated African American Dad (DAAD) Study, a randomized controlled trial (RCT) designed to test a fatherhood intervention against a financial literacy comparison condition. AA nonresident (AANR) fathers are fathers who do not reside with their child on a full-time basis...
May 9, 2018: Public Health Nursing
Zhihua Hua, Paymon Doroodian, William Vu
Ubiquitin (Ub) and Ub-like proteins, collectively forming the ubiquiton family, regulate nearly all aspects of cellular processes via posttranslational modifications. Studies devoted to specific members suggested a large expansion of this family in plants. However, lack of its systematic analysis hinders the comparison of individual members at both evolutionary history and functional divergence levels, which may provide new insight into biological functions. In this work, we first retrieved in total 5,856 members of 17 known ubiquiton subfamilies in 50 plant genomes by searching both prior annotations and missing loci in each genome...
May 8, 2018: Plant Journal: for Cell and Molecular Biology
Ismail Koyuncu, Abdurrahman Kocyigit, Ahmet Ozer, Sahabettin Selek, Adnan Kirmit, Hasan Karsen
Serologic tests for brucellosis aim to detect antibodies produced against membranous lipopolysaccharide of bacteria. Diagnostic use of this method is limited due to false positiveness. This study evaluates an alternative antigen to lipopolysaccharides (LPS), outer membrane 28-precursor-protein, of Brucella melitensis Rev1 for its diagnostic value. Omp28 precursor of B. melitensis Rev1 was cloned, expressed, and purified. 6-His and sumo epitope tags were used to tag the protein at N-termini. Omp28 gene was amplified based on the ORF sequence and cloned into a pETSUMO vector...
2018: Central-European Journal of Immunology
Junyi Chen, Kamila Kalinowska, Benedikt Müller, Julia Mergner, Rainer Deutzmann, Claus Schwechheimer, Ulrich Z Hammes, Thomas Dresselhaus
Embryogenesis in flowering plants is initiated by an asymmetric zygote division, generating two daughter cells that are the precursors of different cell lineages. Little is known about the molecular players regulating activation and progression of zygote development, establishment of asymmetry, and the plant-specific process of cell-plate formation. Here, we report the function of the ubiquitin-like modifier DiSUMO-LIKE (DSUL) for early embryo development in maize. Introducing a DSUL-RNAi construct by sperm cells affects cytokinesis generating non-separated zygotic daughter nuclei or multinucleate embryonic cells lacking cell plates...
April 26, 2018: Current Biology: CB
Matt Greenlee, Annabel Alonso, Maliha Rahman, Nida Meednu, Kayla Davis, Victoria Tabb, River Cook, Rita K Miller
Stu2p is the yeast member of the XMAP215/Dis1/ch-TOG family of microtubule-associated proteins that promote microtubule polymerization. However, the factors that regulate its activity are not clearly understood. Here we report that Stu2p in the budding yeast Saccharomyces cerevisiae interacts with SUMO by covalent and non-covalent mechanisms. Stu2p interacted by two-hybrid analysis with the yeast SUMO Smt3p, its E2 Ubc9p, and the E3 Nfi1p. A region of Stu2p containing the dimerization domain was both necessary and sufficient for interaction with SUMO and Ubc9p...
May 5, 2018: Cytoskeleton
Valérie Lallemand-Breitenbach, Hugues de Thé
PML nuclear bodies are nucleated by the PML protein, which polymerizes into spherical shells where it concentrates many unrelated partner proteins. Emerging data has connected PML bodies to post-translational control, notably conjugation by SUMOs. High concentrations of SUMO-bound proteins were proposed to condense into liquid-like droplets and such phase transition may occur within NBs. Many stress pathways modulate NB formation and recent findings have directly implicated PML in oxidative stress response in vivo...
April 30, 2018: Current Opinion in Cell Biology
Hua-Rong Luo, Ying Liu, Xiao-Dong Wan, Jun-Liang Li, Min Wu, Qi-Min Zhang, Deng-Long Wu, Xin Zhao, Tian-Ru Wang
BACKGROUND/AIMS: SUMOylation is a dynamic process and reversed by the activity of SUMO-specific proteases (SENPs) family. SENP1, a member of this family, is highly expressed and plays oncogenic roles in diverse cancers including prostate cancer. However, the SENP1-transgenic mice exhibit aberrant transformation of the mouse prostate gland but do not develop cancer. Cellular Stress Response 1 (CSR1) is a tumor suppressor gene and frequently deleted in prostate cancers. Overexpression of CSR1 in prostate cancer cells inhibits colony formation, anchorage-independent growth and induces cell death...
April 25, 2018: Cellular Physiology and Biochemistry
Taishi Midorikawa, Megumi Ohta, Suguru Torii, Shizuo Sakamoto
It is difficult to precisely and easily estimate the changes in skeletal muscle mass (SMM) following exercise training. We aimed to assess whether the change in lean soft tissue mass measured using dual-energy X-ray absorptiometry (DXA) reflects the change in SMM measured using magnetic resonance imaging (MRI) following exercise training in both the leg and trunk regions. Anthropometry, DXA, and MRI measurements of the trunk and leg regions were obtained in 10 male college sumo wrestlers before and after exercise training (mean duration between measurements: ~2 yr)...
April 4, 2018: Journal of Clinical Densitometry
Liu-Zhong Jin, Ji-Shou Lu, Jian-Wen Gao
Objective: Intervertebral disc degeneration (IDD), as a common cause of back pain, is related to the promotion of cellular senescence and reduction in proliferation. Based on recent studies, small ubiquitin-related modifier (SUMO) proteins have been implicated in various biological functions. Therefore, in the present study, we investigated the effects of SUMO2 on proliferation and senescence of nucleus pulposus cells (NPCs) via mediation of p53 signaling pathway in rat models of IDD. Methods: After the establishment of the rat models of IDD for the measurement of positive expression of SUMO2/3 protein, the mRNA and protein levels of SUMO2, molecular phenotype (MMP-2 and HIF-1α) and p53 signaling pathway-related genes (p21, MDM2, GADD45a, CDK2/4 and CyclinB1) were determined, followed by the detection of cell proliferation, cell cycle, apoptosis, and cell senescence...
April 26, 2018: Bioscience Reports
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