oalib
Search Results: 1 - 10 of 100 matches for " "
All listed articles are free for downloading (OA Articles)
Page 1 /100
Display every page Item
SUMO-SIM Interactions Regulate the Activity of RGSZ2 Proteins  [PDF]
Javier Garzón, María Rodríguez-Mu?oz, Ana Vicente-Sánchez, María ángeles García-López, Ricardo Martínez-Murillo, Thierry Fischer, Pilar Sánchez-Blázquez
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0028557
Abstract: The RGSZ2 gene, a regulator of G protein signaling, has been implicated in cognition, Alzheimer's disease, panic disorder, schizophrenia and several human cancers. This 210 amino acid protein is a GTPase accelerating protein (GAP) on Gαi/o/z subunits, binds to the N terminal of neural nitric oxide synthase (nNOS) negatively regulating the production of nitric oxide, and binds to the histidine triad nucleotide-binding protein 1 at the C terminus of different G protein-coupled receptors (GPCRs). We now describe a novel regulatory mechanism of RGS GAP function through the covalent incorporation of Small Ubiquitin-like MOdifiers (SUMO) into RGSZ2 RGS box (RH) and the SUMO non covalent binding with SUMO-interacting motifs (SIM): one upstream of the RH and a second within this region. The covalent attachment of SUMO does not affect RGSZ2 binding to GPCR-activated GαGTP subunits but abolishes its GAP activity. By contrast, non-covalent binding of SUMO with RH SIM impedes RGSZ2 from interacting with GαGTP subunits. Binding of SUMO to the RGSZ2 SIM that lies outside the RH does not affect GαGTP binding or GAP activity, but it could lead to regulatory interactions with sumoylated proteins. Thus, sumoylation and SUMO-SIM interactions constitute a new regulatory mechanism of RGS GAP function and therefore of GPCR cell signaling as well.
SUMO-1 possesses DNA binding activity
Sebastian Eilebrecht, Caroline Smet-Nocca, Jean-Michel Wieruszeski, Arndt Benecke
BMC Research Notes , 2010, DOI: 10.1186/1756-0500-3-146
Abstract: Using NMR spectroscopy and protein-DNA cross-linking experiments, we demonstrate here that SUMO-1 can specifically interact with dsDNA in a sequence-independent fashion. We also show that SUMO-1 binding to DNA can compete with other protein-DNA interactions at the example of the regulatory domain of Thymine-DNA Glycosylase and, based on these competition studies, estimate the DNA binding constant of SUMO1 in the range 1 mM.This finding provides an important insight into how SUMO-1 might exert its activity. SUMO-1 might play a general role in destabilizing DNA bound protein complexes thereby operating in a bottle-opener way of fashion, explaining its pivotal role in regulating the activity of many central transcription and DNA repair complexes.Ubiquitin and small ubiquitin-like modifiers (SUMOs) form a family of structurally related proteins that often become covalently attached to other cellular factors. This post-translational modification of proteins, usually on lysine residues, with ubiquitin and SUMOs changes the functional properties of their targets [1-15]. Both, the regulation of the target's enzymatic activity and the modification of interaction patterns with third partners such as proteins and DNA have been described. Thereby, sumoylation apparently also provides a means to recruit SUMO interacting proteins via their SUMO binding motifs (SBMs) to the sumoylated target [16]. Furthermore, sumoylation and SUMO association have been found to influence other post-translational modifications such as phosphorylation. Sumoylation is an energy-dependent process carried out by a dedicated enzymatic machinery which is similar in composition and activity to the ubiquitination apparatus [2-7,9,10]. SUMO-specific proteases (SENPs) can reverse the process of sumoylation. Sumoylation has an essential role in most organisms. Deletion or inactivation of SUMOs or enzymes involved in the sumoylation process lead to severe growth defects in yeast or embryonic lethality in mice
Global SUMO Proteome Responses Guide Gene Regulation, mRNA Biogenesis, and Plant Stress Responses  [PDF]
Magdalena J. Mazur,Harrold A. van den Burg
Frontiers in Plant Science , 2012, DOI: 10.3389/fpls.2012.00215
Abstract: Small Ubiquitin-like MOdifier (SUMO) is a key regulator of abiotic stress, disease resistance, and development in plants. The identification of >350 plant SUMO targets has revealed many processes modulated by SUMO and potential consequences of SUMO on its targets. Importantly, highly related proteins are SUMO-modified in plants, yeast, and metazoans. Overlapping SUMO targets include heat-shock proteins (HSPs), transcription regulators, histones, histone-modifying enzymes, proteins involved in DNA damage repair, but also proteins involved in mRNA biogenesis and nucleo-cytoplasmic transport. Proteomics studies indicate key roles for SUMO in gene repression by controlling histone (de)acetylation activity at genomic loci. The responsible heavily sumoylated transcriptional repressor complexes are recruited by plant transcription factors (TFs) containing an (ERF)-associated Amphiphilic Repression (EAR) motif. These TFs are not necessarily themselves a SUMO target. Conversely, SUMO acetylation (Ac) prevents binding of downstream partners by blocking binding of their SUMO-interaction peptide motifs to Ac-SUMO. In addition, SUMO acetylation has emerged as a mechanism to recruit specifically bromodomains. Bromodomains are generally linked with gene activation. These findings strengthen the idea of a bi-directional sumo-acetylation switch in gene regulation. Quantitative proteomics has highlighted that global sumoylation provides a dynamic response to protein damage involving SUMO chain-mediated protein degradation, but also SUMO E3 ligase-dependent transcription of HSP genes. With these insights in SUMO function and novel technical advancements, we can now study SUMO dynamics in responses to (a)biotic stress in plants.
A Non-Coding RNA Promotes Bacterial Persistence and Decreases Virulence by Regulating a Regulator in Staphylococcus aureus  [PDF]
Cédric Romilly equal contributor,Claire Lays equal contributor,Arnaud Tomasini,Isabelle Caldelari,Yvonne Benito,Philippe Hammann,Thomas Geissmann,Sandrine Boisset,Pascale Romby ,Fran?ois Vandenesch
PLOS Pathogens , 2014, DOI: doi/10.1371/journal.ppat.1003979
Abstract: Staphylococcus aureus produces a high number of RNAs for which the functions are poorly understood. Several non-coding RNAs carry a C-rich sequence suggesting that they regulate mRNAs at the post-transcriptional level. We demonstrate that the Sigma B-dependent RsaA RNA represses the synthesis of the global transcriptional regulator MgrA by forming an imperfect duplex with the Shine and Dalgarno sequence and a loop-loop interaction within the coding region of the target mRNA. These two recognition sites are required for translation repression. Consequently, RsaA causes enhanced production of biofilm and a decreased synthesis of capsule formation in several strain backgrounds. These phenotypes led to a decreased protection of S. aureus against opsonophagocytic killing by polymorphonuclear leukocytes compared to the mutant strains lacking RsaA. Mice animal models showed that RsaA attenuates the severity of acute systemic infections and enhances chronic catheter infection. RsaA takes part in a regulatory network that contributes to the complex interactions of S. aureus with the host immune system to moderate invasiveness and favour chronic infections. It is the first example of a conserved small RNA in S. aureus functioning as a virulence suppressor of acute infections. Because S. aureus is essentially a human commensal, we propose that RsaA has been positively selected through evolution to support commensalism and saprophytic interactions with the host.
Regulation of cel Genes of C. cellulolyticum: Identification of GlyR2, a Transcriptional Regulator Regulating cel5D Gene Expression  [PDF]
Imen Fendri, Laetitia Abdou, Valentine Trotter, Luc Dedieu, Hédia Maamar, Nigel P. Minton, Chantal Tardif
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0044708
Abstract: Transcription and expression regulation of some individual cel genes (cel5A, cel5I, cel5D and cel44O) of Clostridium cellulolyticum were investigated. Unlike the cip-cel operon, these genes are transcribed as monocistronic units of transcription, except cel5D. The location of the transcription initiation sites was determined using RT-PCR and the mRNA 5′-end extremities were detected using primer extension experiments. Similarly to the cip-cel operon, cel5A and cel5I expressions are regulated by a carbon catabolite repression mechanism, whereas cel44O and cel5D expressions do not seem to be submitted to this regulation. The role of the putative transcriptional regulator GlyR2 in the regulation of cel5D expression was investigated. The recombinant protein GlyR2 was produced and was shown to bind in vitro to the cel5D and glyR2 promoter regions, suggesting that besides regulating its own expression, GlyR2 may regulate cel5D expression. To test this hypothesis in vivo, an insertional glyR2 mutant was generated and the effect of this disruption on cel5D expression was evaluated. Levels of cel5D mRNAs in the mutant were 16 fold lower than that of the wild-type strain suggesting that GlyR2 acts as an activator of cel5D expression.
SUMO Wrestles with Recombination  [PDF]
Veronika Altmannová,Peter Kolesár,Lumír Krej?í
Biomolecules , 2012, DOI: 10.3390/biom2030350
Abstract: DNA double-strand breaks (DSBs) comprise one of the most toxic DNA lesions, as the failure to repair a single DSB has detrimental consequences on the cell. Homologous recombination (HR) constitutes an error-free repair pathway for the repair of DSBs. On the other hand, when uncontrolled, HR can lead to genome rearrangements and needs to be tightly regulated. In recent years, several proteins involved in different steps of HR have been shown to undergo modification by small ubiquitin-like modifier (SUMO) peptide and it has been suggested that deficient sumoylation impairs the progression of HR. This review addresses specific effects of sumoylation on the properties of various HR proteins and describes its importance for the homeostasis of DNA repetitive sequences. The article further illustrates the role of sumoylation in meiotic recombination and the interplay between SUMO and other post-translational modifications.
Emerging roles of the SUMO pathway in mitosis
Mary Dasso
Cell Division , 2008, DOI: 10.1186/1747-1028-3-5
Abstract: SUMO proteins are small ubiquitin-like modifiers that become covalently conjugated to cellular proteins. In budding yeast, proteomic experiments indicate that 300 or more proteins may be SUMOylation targets [1-4]. This post-translational modification controls multiple events, including transcription, DNA repair, DNA recombination and mitotic chromosome segregation. The three former processes were covered within recent reviews [5-11], and will not be discussed here. Rather, I will focus on evidence that SUMOylation plays a critical role in mitotic chromosome structure and segregation, and on how this pathway may be regulated during mitosis.There is one SUMO protein in S. cerevisiae (Smt3p) and S. pombe (Pmt3), but mammalian cells typically express three SUMO paralogues (SUMO1-3) [12]. Like ubiquitin, newly translated SUMOs require cleavage to reveal C-terminal diglycine motifs (Figure 1, Step 1). After maturation, SUMO1 is ~45% identical to SUMO2 or 3, while SUMO2 and 3 are ~95% identical to each other. Where they cannot be distinguished, I will refer to SUMO2 and 3 collectively as SUMO2/3. Proteases of the Ubiquitin like protein protease/Sentrin specific proteases (Ulp/SENPs) family catalyze SUMO processing [13]. S. cerevisiae has two Ulp/SENPs (Ulp1p and Ulp2p/Smt4p). Ulp1p associates with the nuclear envelope [14], and is important for Smt3p maturation [15]. S. pombe likewise has two Ulp/SENPs (also called Ulp1 and Ulp2), while mammals have six (SENP1, 2, 3, 5, 6 and 7) [13].Conjugation of mature SUMOs occurs through a cascade (Figure 1, Steps 2–4) containing a heterodimeric activating enzyme (E1 enzyme. Uba2/Aos1), a conjugating enzyme (E2 enzyme. Ubc9) and usually a SUMO ligase (E3 enzyme) [12]. Nomenclature of SUMO pathway enzymes in yeast and vertebrates are given in Table 1. The result of these reactions is an isopeptide linkage between the SUMO C-terminal glycine and an ε-amino group of a lysine within the target protein. The biochemistry of SUMO and ubiquit
At the crossroads of SUMO and NF-κB
Martin P Kracklauer, Christian Schmidt
Molecular Cancer , 2003, DOI: 10.1186/1476-4598-2-39
Abstract: SUMO-IκBα localizes in the nucleus. The nuclear SUMO-IκBα pool may be dynamic. SUMO-IκBα functions as synergy control factor.Immunoprecipitation from cellular fractions, 35S methionine pulse-chase, and FRET assays should reveal the localization of SUMO-IκBα and the dynamics of the pool. Expression of SUMOylation defective IκBα in an IκBα -/- background should yield insights into the function of SUMO-IκBα.IκBα contains the required SUMOylation motif but IκBβ does not. The suggested study would provide evidence whether or not IκBα and IκBβ can substitute each other. In addition, the suggested assays would reveal a possible redundancy in controlling transcriptional activity of NF-κB.For nearly two decades, the NF-κB activation pathway has been the focus of experimental investigation. This pathway is highly conserved among metazoans and plays key roles in immune responses [1], cell proliferation [2], inflammation [3], apoptosis [4], early embryonic development [5], and many other processes.Five members of mammalian NF-κB are described: NF-κB1 (p50 and its precursor p105), NF-κB2 (p52 and its precursor p100), c-Rel, RelA (p65) and RelB [6-9], each of which has a 300-residue Rel homology domain (RHD) [1,10-14]. The C-terminal domains are responsible for dimerization with other Rel proteins, but sequence-specific interactions come primarily from loops in the N-terminal domain [15].Interaction of c-Rel, RelA and RelB with its inhibitors, referred to as IκB, results in inactive complexes in the cytoplasm by masking the nuclear localization signal, which is located at the C terminal end of the Rel homology domain [1,10-14]. Currently, the inhibitor proteins IκBα, IκBβ, IκBγ, IκBε, Bcl-3, and the Drosophila protein Cactus are described and characterized [1,10-14].In most cell types, NF-κB proteins are sequestered in the cytoplasm in an inactive form through their non-covalent association with the inhibitor IκB [7]. This association masks the nuclear localization signal of NF-κ
Sumo-dependent substrate targeting of the SUMO protease Ulp1
Zachary C Elmore, Megan Donaher, Brooke C Matson, Helen Murphy, Jason W Westerbeck, Oliver Kerscher
BMC Biology , 2011, DOI: 10.1186/1741-7007-9-74
Abstract: Using a structure/function approach, we set out to elucidate features of Ulp1 that are required for substrate targeting. To aid our studies, we took advantage of a catalytically inactive mutant of Ulp1 that is greatly enriched at the septin ring of dividing yeast cells. We found that the localization of Ulp1 to the septins requires both SUMO and specific structural features of Ulp1's catalytic domain. Our analysis identified a 218-amino acid, substrate-trapping mutant of the catalytic domain of Ulp1, Ulp1(3)(C580S), that is necessary and sufficient for septin localization. We also used the targeting and SUMO-binding properties of Ulp1(3)(C580S) to purify Smt3-modified proteins from cell extracts.Our study provides novel insights into how the Ulp1 SUMO protease is actively targeted to its substrates in vivo and in vitro. Furthermore, we found that a substrate-trapping Ulp1(3)(C580S) interacts robustly with human SUMO1, SUMO2 and SUMO2 chains, making it a potentially useful tool for the analysis and purification of SUMO-modified proteins.Cell division is a fundamental feature of all life and involves the controlled duplication and faithful segregation of an organism's genetic material from one cell to the next. In eukaryotes, each cell division cycle is therefore executed as a tightly regulated, stepwise program that relies on intact chromosomes. In humans, the consequences of faulty chromosome segregation and the inability to repair DNA damage have been implicated in cancer, aging and congenital birth defects.Ubiquitin and small ubiquitin-like modifier (SUMO), two small proteins that can become attached to other cellular proteins in a reversible manner [1], control important aspects of the cell division program. Ubiquitin is best known for its role in the targeted, proteasome-mediated destruction of proteins, including key cell-cycle regulators, but also holds nonproteolytic functions [2]. Sumoylation, on the other hand, does not directly target proteins for degradat
植物SUMO化修饰及其生物学功能  [PDF]
徐庞连;曾棉炜;黄丽霞;阳成伟*
植物学报 , 2008,
Abstract: ?SUMO化修饰是细胞内蛋白质功能调节的重要方式之一。植物中的SUMO化修饰途径由SUMO分子和SUMO化酶系组成。SUMO化修饰是一个可逆的动态过程。SUMO前体蛋白在SUMO特异性蛋白酶的作用下成熟,随后通过SUMO活化酶、SUMO结合酶和SUMO连接酶将靶蛋白SUMO化,最后SUMO特异性蛋白酶将SUMO与靶蛋白分离,重新进入SUMO化循环。初步研究表明,植物SUMO化修饰参与植物花期调控、激素信号转导、抗病防御以及逆境应答等生理过程。
Page 1 /100
Display every page Item


Home
Copyright © 2008-2017 Open Access Library. All rights reserved.