The Experts below are selected from a list of 54 Experts worldwide ranked by ideXlab platform
Stephen J Elledge - One of the best experts on this subject based on the ideXlab platform.
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the SUMO 1 isopeptidase smt4 is linked to centromeric cohesion through SUMO 1 modification of dna topoisomerase ii
Molecular Cell, 2002Co-Authors: Jeff Bachant, Annette A Alcasabas, Yuval Blat, Nancy Kleckner, Stephen J ElledgeAbstract:In S. cerevisiae, posttranslational modification by the ubiquitin-like Smt3/SUMO-1 Protein is essential for survival, but functions and cellular targets for this modification are largely unknown. We find that one function associated with the Smt3/SUMO-1 isopeptidase Smt4 is to control chromosome cohesion at centromeric regions and that a key Smt3/SUMO-1 substrate underlying this function is Top2, DNA Topoisomerase II. Top2 modification by Smt3/SUMO-1 is misregulated in smt4 strains, and top2 mutants resistant to Smt3/SUMO-1 modification suppress the smt4 cohesion defect. top2 mutants display aberrant chromatid stretching at the centromere in response to mitotic spindle tension and altered chromatid reassociation following microtubule depolymerization. These results suggest Top2 modification by Smt3/SUMO-1 regulates a component of chromatin structure or topology required for centromeric cohesion.
Markus Engstler - One of the best experts on this subject based on the ideXlab platform.
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the dna topoisomerase i binding Protein topors as a novel cellular target for SUMO 1 modification characterization of domains necessary for subcellular localization and SUMOlation
Experimental Cell Research, 2003Co-Authors: Stefan Weger, Eva Hammer, Markus EngstlerAbstract:Abstract Over the past years, modification by covalent attachment of SUMO (small ubiquitin-like modifier) has been demonstrated for of a number of cellular and viral Proteins. While increasing evidence suggests a role for SUMO modification in the regulation of Protein–Protein interactions and/or subcellular localization, most SUMO targets are still at large. In this report we show that Topors, a Topoisomerase I and p53 interacting Protein of hitherto unknown function, presents a novel cellular target for SUMO-1 modification. In a yeast two-hybrid system, Topors interacted with both SUMO-1 and the SUMO-1 conjugating enzyme UBC9. Multiple SUMO-1 modified forms of Topors could be detected after cotransfection of exogenous SUMO-1 and Topors induced the colocalization of a YFP tagged SUMO-1 Protein in a speckled pattern in the nucleus. A subset of these Topors' nuclear speckles were closely associated with the PML nuclear bodies (POD, ND10). A central domain comprising Topors residues 437 to 574 was sufficient for both SUMOlation and localization to nuclear speckles. One SUMO-1 acceptor site at lysine residue 560 could be identified within this region. However, SUMOlation-deficient Topors mutants showed that SUMOlation obviously is not required for localization to nuclear speckles.
Anne Dejean - One of the best experts on this subject based on the ideXlab platform.
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viral immediate early Proteins abrogate the modification by SUMO 1 of pml and sp100 Proteins correlating with nuclear body disruption
Journal of Virology, 1999Co-Authors: Stefan Muller, Anne DejeanAbstract:PML nuclear bodies (NBs) are subnuclear structures whose integrity is compromised in certain human diseases, including leukemia and neurodegenerative disorders. Infection by a number of DNA viruses similarly triggers the reorganization of these structures, suggesting an important role for the NBs in the viral infection process. While expression of the adenovirus E4 ORF3 Protein leads to only a moderate redistribution of PML to filamentous structures, the herpes simplex virus (HSV) ICP0 Protein and the cytomegalovirus (CMV) IE1 Protein both induce a complete disruption of the NB structure. Recently, we and others have shown that the NB Proteins PML and Sp100 are posttranslationally modified by covalent linkage with the ubiquitin-related SUMO-1 Protein and that this modification may promote the assembly of these structures. Here we show that the HSV ICP0 and CMV IE1 Proteins specifically abrogate the SUMO-1 modification of PML and Sp100, whereas the adenovirus E4 ORF3 Protein does not affect this process. The potential of ICP0 and IE1 to alter SUMO-1 modification is directly linked to their capacity to disassemble NBs, thus strengthening the role for SUMO-1 conjugation in maintenance of the structural integrity of the NBs. This observation supports a model in which ICP0 and IE1 disrupt the NBs either by preventing the formation or by degrading of the SUMO-1-modified PML and Sp100 Protein species. Finally, we show that the IE1 Protein itself is a substrate for SUMO-1 modification, thus representing the first viral Protein found to undergo this new type of posttranslational modification.
Oleg Melnyk - One of the best experts on this subject based on the ideXlab platform.
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a central cysteine residue is essential for the thermal stability and function of SUMO 1 Protein and SUMO 1 peptide Protein conjugates
Bioconjugate Chemistry, 2016Co-Authors: Herve Drobecq, Emmanuelle Boll, Magalie Senechal, Remi Desmet, Jeanmichel Saliou, Jeanjacques Lacapere, Alexandra Mougel, Jerome Vicogne, Oleg MelnykAbstract:SUMOylation constitutes a major post-translational modification (PTM) used by the eukaryote cellular machinery to modulate Protein interactions of the targeted Proteins. The small ubiquitin-like modifier-1 (SUMO-1) features a central and conserved cysteine residue (Cys52) that is located in the hydrophobic core of the Protein and in tight contact with Phe65, suggesting the occurrence of an S/π interaction. To investigate the importance of Cys52 on SUMO-1 thermal stability and biochemical properties, we produced by total chemical synthesis SUMO-1 or SUMO-1 Cys52Ala peptide-Protein conjugates featuring a native isopeptidic bond between SUMO-1 and a peptide derived from p53 tumor suppressor Protein. The Cys52Ala modification perturbed SUMO-1 secondary structure and resulted in a dramatic loss of Protein thermal stability. Moreover, the cleavage of the isopeptidic bond by the deconjugating enzyme Upl1 was significantly less efficient than for the wild-type conjugate. Similarly, the in vitro SUMOylation of RanGap1 by E1/E2 conjugating enzymes was significantly less efficient with the SUMO-1 C52A analog compared to wild-type SUMO-1. These data demonstrate the critical role of Cys52 in maintaining SUMO-1 conformation and function and the importance of keeping this cysteine intact for the study of SUMO-1 Protein conjugates.
Stefan Weger - One of the best experts on this subject based on the ideXlab platform.
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the dna topoisomerase i binding Protein topors as a novel cellular target for SUMO 1 modification characterization of domains necessary for subcellular localization and SUMOlation
Experimental Cell Research, 2003Co-Authors: Stefan Weger, Eva Hammer, Markus EngstlerAbstract:Abstract Over the past years, modification by covalent attachment of SUMO (small ubiquitin-like modifier) has been demonstrated for of a number of cellular and viral Proteins. While increasing evidence suggests a role for SUMO modification in the regulation of Protein–Protein interactions and/or subcellular localization, most SUMO targets are still at large. In this report we show that Topors, a Topoisomerase I and p53 interacting Protein of hitherto unknown function, presents a novel cellular target for SUMO-1 modification. In a yeast two-hybrid system, Topors interacted with both SUMO-1 and the SUMO-1 conjugating enzyme UBC9. Multiple SUMO-1 modified forms of Topors could be detected after cotransfection of exogenous SUMO-1 and Topors induced the colocalization of a YFP tagged SUMO-1 Protein in a speckled pattern in the nucleus. A subset of these Topors' nuclear speckles were closely associated with the PML nuclear bodies (POD, ND10). A central domain comprising Topors residues 437 to 574 was sufficient for both SUMOlation and localization to nuclear speckles. One SUMO-1 acceptor site at lysine residue 560 could be identified within this region. However, SUMOlation-deficient Topors mutants showed that SUMOlation obviously is not required for localization to nuclear speckles.
