Sumoylation ppt to pdf

Download fulltext pdf download fulltext pdf pml, sumoylation, and senescence article pdf available in frontiers in oncology 3. Several nuclear receptor nr superfamily members are known to be the molecular target of either the small ubiquitinrelated modifier sumo or ubiquitinsignaling pathways. Sumoylationmediated regulation of cell cycle progression. The regulatory role of sumoylation, the attachment of a small ubiquitinrelated modifier to a target protein, has been.

Sumoylation and human disease pathogenesis sciencedirect. Sumoylation increases the expression of genes linked with adaptation to hypoxia cluster i and ii, while reducing genes that act as activators of cellular functions cluster iii. In many cases, sumoylation of transcriptional regulators correlates with inhibition of transcription. Sumoylation is a posttranslational modification involved in various cellular processes, such as nuclearcytosolic transport, transcriptional regulation, apoptosis, protein stability, response to stress, and. Attachment of sumo to target proteins occurs via a number of specific activating and. Desumoylation and aggregation are two crucial steps required for the translation of the mrna targets of cpeb3 and for dendritic filopodia formation. Ulps are also required for generating mature sumo from the sumo precursor, which contains a short peptide blocking its c terminus. Nov, 2014 protein sumoylation plays an important role in regulation of many cellular processes. Global protein sumoylation and expression of components in sumoylation pathway were recently found to be altered in the process of organismal aging. Download figure open in new tab download powerpoint. The posttranslational addition of small ubiquitinlike modifiers sumos to other intracellular proteins has been implicated in a variety of eukaryotic functions, including modifying cytoplasmic signal transduction, nuclear import and subnuclear compartmentalization, dna repair, and transcription regulation.

Small ubiquitinrelated modifier sumo is a protein moiety that is ligated to. Sumoylation pathway is required to maintain the basal. The sumo e3 protein pias3 protein inhibitor of activated stat3 is upregulated in a number of different cancer. Small ubiquitinrelated modifier sumo proteins are members of ubiquitinlike superfamily proteins that can be covalently. In cancer, myc overexpression is often associated with aggressive disease, which is in part due to the destruction of select targets by the ubiquitinproteasome system eg, scf skp2directed destruction of the cdk inhibitor p27 kip1. The identification of sumoylation sites and sumointeraction. Structural analysis suggests that the phd finger and the bromodomain cooperate as an integrated unit to recruit ubc9 and facilitate sumoylation zeng et al. Gestational trophoplastic tumors list of high impact. Protein sumoylation regulates multiple processes involved in the differentiation and maturation of cells and tissues during development. A chemical and enzymatic approach to study sitespecific. Largescale analysis of lysine sumoylation by sumo remnant.

Sumoylation is directed by an enzymatic cascade analogous to that involved in ubiquitination. We applied this method to analyze the autosumoylation of the e1 enzyme in. Clarke as, lowell je, jacobson sj, pillus l 1999 esa1p is an essential histone acetyltransferase required for cell cycle progression. Sumoylation is an essential ubiquitin like modification involved in important biological processes in eukaryotic cells. The modification involves the covalent attachment of a 12kda sumo small ubiquitinlike. The molecular and biochemical mechanisms involved in sumoylation have been the subject of intense interest in recent years. Lectures notes in bioinformatics, volume 52652008, pp 2840, springer prib 2008. The performance under these three thresholds was presented. It presents information on the history, evolution and mechanis. In contrast to ubiquitination, however, sumoylation does not promote. Lkb1 sumoylation is augmented in preclinical mouse models and clinical hcc, being a hallmark of more aggressive hcc tumors. Sumoylation and desumoylation at a glance journal of cell science.

Sumoylation is one of the posttranslational modifications commonly seen in proteins this involves the covalent binding of a peptide called sumo to specific sites on the proteins made up of lysine amino acids sumoylation occurs in three stages and involves 2 to 3 catalytic enzymes maturation. Histone modification table cell signaling technology. Sumoylation at chromatin governs coordinated repression of a transcriptional program essential for cell growth and proliferation by neyret kahn et al, 20 presntation as course requirement for molecular biology course bs2002 university of east london and presented by girma berhanu, saron woldemichael and vera ezenwa. Myc oncogenic transcription factors cmyc, nmyc, and lmyc coordinate the control of cell growth, division, and metabolism. In addition, key factors controlling cellular senescence are known to be sumoylated. All the spaces, line breaks will be automatically removed. Mycinduced sumoylation is a therapeutic vulnerability for.

People can view the slides even if they dont have powerpoint, but they cant make changes to it. A posttranslational modification targeting cytoskeletal proteins related publications. Protein sumoylation modification and its associations with disease. A sumoylationdependent transcriptional subprogram is. The dynamic sumoylation pattern observed throughout the cell cycle is ensured via distinct spatial and temporal regulation of the sumo machinery. Sumoylation in neurodegenerative diseases abstract. Mar 11, 2009 covalent modification by sumo polypeptides, or sumoylation, is an important regulator of the functional properties of many proteins.

The sumoylation pathway is dysregulated in multiple. Pdf converter is a online webbased document to pdf converter software. Charts depicting the percentage of different types of proteins targeted for sumoylation as determined by proteomic analyses. Sumoylation in cellular senescence and aging volume.

This poster article discusses the enzymes that mediate sumoylation and desumoylation, concentrating on their. For plants, in particular, both genetic analyses and the rapid accumulation of. Here we monitor the expression of key sumo pathway proteins and levels of substrate protein sumoylation in. Interplay between phosphorylation and sumoylation events.

Sumoylation sitesim prediction bioinformatics tools omicx. This volume, edited and written by leading international experts, is the first book to be devoted to sumoylation. Among these are several proteins implicated in human diseases including cancer, huntingtons, alzheimers, and parkinsons diseases, as well as spinocerebellar ataxia 1 and amyotrophic lateral sclerosis. Sumoylation of target proteins in vivo has been shown to cause a number of different outcomes, including altered localization and binding partners. Sumoylation is a reversible posttranslational modification that. Kimura a, horikoshi m 1998 tip60 acetylates six lysines of a specific class in core histones in vitro. Further supporting the importance of sumoylation are studies that have implicated a role for small ubiquitinlike modifier sumo modification in human diseases. Sumoylation regulates the functional properties of a large number of proteins and thereby plays a very important role in the normal functions of cells. The other major cytoskeletal protein targeted by sumos is tubulin.

Biochemical and biophysical research communications. Sumoylation in gene regulation and cardiac disease. Protein sumoylation plays an important role in regulation of many cellular processes. By covalently modifying specific lysine residues in protein substrates, or by noncovalently interacting with proteins, small ubiquitinlike modifiers sumos play an essential role in the regulation of a variety of biological processes, including gene expression, dna repair, chromosome assembly, and cellular signaling geissfriedlander and melchior, 2007. The atr atm ataxia telangiectasiamutated and rad3related checkpoint is a crucial dna damage signaling pathway. The subsequent deconjugation of sumo from target proteins is conducted by a class of enzymes termed sumo proteases. Sumoylation of dnmt1 was first observed as specific shifts in molecular weight as determined by western blot after incubation in a cellfree sumoylation assay, or following coexpression with ubc9 and sumo1 a small ubiquitinlike modifier that is conjugated to its substrate upon catalysis.

Sumoylation promotes survival and integration of neural. Xiao z, chang jg, hendriks ia, sigurethsson jo, olsen jv, vertegaal ac 2015 systemwide analysis of sumoylation dynamics in response to replication stress reveals novel small ubiquitinlike modified target proteins and acceptor lysines relevant for genome stability. Genes cells 312, 789800 schiltz rl, mizzen ca, vassilev a, cook rg, allis cd, nakatani y 1999 overlapping but. Developmental profiles of sumoylation pathway proteins in. The role of sumoylation in the auxin response pathway. Download ppt lkb1 is an upstream activator of ampk promoting the phosphorylation of ampk thr172 in the. Sumoylation regulates lkb1 localization and its oncogenic. Sumoylation of atrip potentiates dna damage signaling by.

Sumoylation is an essential ubiquitinlike modification involved in important biological processes in eukaryotic cells. Listeria monocytogenes impairs sumoylation for efficient. Thus, inhibition of sumoylation may merit investigation as a possible therapy for mycdriven human cancers. However, little is currently known regarding how these two posttranslational modifications interact to control nr biology. Mapping both sumoconjugation sites and sims is required to study the. Recent reports reveal two new examples of human disease. After neuronal stimulation, cpeb3 becomes desumoylated and more aggregated. The development of sumoylation inhibitorsa novel approach to.

Sumoylation is a dynamic process that is mediated by activating e1, conjugating e2, and ligating e3 enzymes and readily reversed by a family of u biquitinl ike proteinspecific p roteases ulp in yeast and sen trinsumospecific p roteases senp in human. Methods plasmids for the nterminal in situtap tag, a part of the tbsumo open reading frame orf was ampli. Interactions in the human and plasmodium falciparum sumo conjugation. Gestational trophoblastic disease gtd is a gathering of uncommon tumors that include unusual development of cells inside a ladys uterus. Covalent modification by sumo polypeptides, or sumoylation, is an important regulator of the functional properties of many proteins. Sumoylation proteins in breast cancer springerlink. The small ubiquitinrelated modifier, sumo1, is a ubiquitinlike family member that is conjugated to its substrates through three discrete enzymatic steps see the figure on the right.

Sumoylation in cellular senescence and aging bentham science. For example, increased ubc9 levels are found in a number of human cancers, and ubc9 overexpression can increase cancer cell growth 25, 26. Myc is an oncogenic transcription factor frequently dysregulated in human cancer. Despite this, relatively little is known about the spatial and temporal regulation of proteins that mediate sumoylation and desumoylation in the cns. Herein, we show that sumoylation of the tfap2a transcription factor is required to maintain the basal breast cancer phenotype. Sumoylation in cellular senescence and aging research. Lamoliatte et e a monoclonal antibody specific for sumo3 tryptic peptides to enhance proteomic. From the evaluation, three thresholds with high, medium and low stringency were chosen for gpssumo. Lee, mingta program in cellular regulation and metabolism, national institute of child health and human development, national institutes of health, bethesda, maryland dasso, mary program in cellular regulation and metabolism, national institute of child health and human development, national institutes of health, bethesda, maryland. Sumoylation of cpeb3 is a constitutive, reversible process in the cell, mediating a physiological function. It is hypothesised that sumo contributes to the aggressive nature of breast cancer. You have also helped to develop and improve my presentation.

Gtd does not create from cells of the uterus like cervical tumor or endometrial uterine coating malignancy do. This effect on sumoylation may support efficient infection by listeria. Sumo proteins are conjugated to a protein substrate, creating an interface for the recruitment of cofactors harboring sumointeracting motifs sims. Inhibiting the sumoylation pathway may be an effective treatment strategy for basal breast cancer. Save powerpoint presentations as pdf files office support. It is becoming apparent that dysregulated sumo contribute to carcinogenesis by affecting posttranscriptional modification of key proteins. Sumoylation is an inhibitory constraint that regulates the. Sumoylation are important for the functions of csb in. The small ubiquitinlike modifier 1 sumo1 protein is a stressinducible posttranslational modification present in all eukaryotic organisms.

There are striking similarities between the machinery that attaches sumo to substrate proteins and the enzymes that participate in ubiquitination fig. A proline90 residue unique to sumo4 prevents maturation and sumoylation. Sumoylation is an essential eukaryotic posttranslational modification that functions in many, predominantly nuclear, cellular processes, such as dna repair and transcription, by regulating target protein localization, stability, or interactions with other proteins or with chromatin 15. Sumoylation is a highly transient posttranslational protein modification. Posttranslational modification by the small ubiquitinlike modifier sumo proteins, a process termed sumoylation, is involved in many fundamental cellular processes. Numerous targets of the sumoylation pathway have been identified downstream from ube2i and pias1, specifically, stat family members, p53 and cjun. Oct 29, 2008 the citation of the corresponding paper. Sumoylation plays critical roles during cell cycle progression. Sumoylation and desumoylation at a glance journal of. Sumoylation stabilizes the association of the bromodomain with the chromatin modifiers, thus promoting the establishment of gene silencing. Apr 08, 2010 numerous targets of the sumoylation pathway have been identified downstream from ube2i and pias1, specifically, stat family members, p53 and cjun. You could input one primary sequence or multiple proteins sequences in fasta format after gpssumo predictor model was welltrained, we performed an evaluation on this model. Ubiquitin and sumo are each covalently attached to substrate proteins via an isopeptide bond between a cterminal glycine in the ubl and a lysine residue in the substrate. Mapping of sumo sites and analysis of sumoylation changes.

Sep 25, 2014 myc oncogenic transcription factors cmyc, nmyc, and lmyc coordinate the control of cell growth, division, and metabolism. Sumoylation of rac1, a rho family gtpase, is mediated by the sumo e3 ligase, pias3, and is necessary for increases in rac1. Click create pdf xps document, then click create pdf xps. Small ubiquitinlike modifier proteins or sumo modify the function of protein substrates involved in various cellular processes including dna damage response ddr. Conjugation of this modifier to a target protein results in the alteration of target protein function. Sumoylation, much of a similar process like ubiquitination catches attention across various research groups as a potential therapeutic target to fight various infectious and cancerous diseases.

Convert and create pdf from various types of files like word doc, excel xls, powerpoint ppt. To identify pathways supporting the myc oncogenic program, we used a genomewide rna interference screen to search for mycsynthetic lethal genes and uncovered a role for the sumoactivating enzyme sae12. Altogether, these genetic and metabolic changes lead to increased resistance to ogdrog in both undifferentiated and differentiated ubc9 nscs in vitro, as well as a. We show that sumo and ubiquitin circuitry coordinately modifies the pregnane x receptor pxr. In the publish as pdf or xps dialog box, choose a location to save the file to. Our data suggest that pol2 sumoylation occurs during replication. Many important cell cycle regulators, including many oncogenes and tumor suppressors, are functionally regulated via sumoylation. During infection, pathogenic bacteria manipulate the host cell in various ways to allow their own replication, propagation. Sumoylation of ephb1 suppresses neuroblastoma tumorigenesis. Sumo enzymatic cascade catalyzes the dynamic posttranslational modification process of sumoylation i. Epiquik in vivo universal protein sumoylation assay kit. Small ubiquitinlike modifier or sumo proteins are a family of small proteins that are covalently attached to and detached from other proteins in cells to modify their function. The cterminal region and sumoylation of cockayne syndrome.

Sumoylation at chromatin represses cell growth and. Sumoylation pathway accessscience from mcgrawhill education. While the atr pathway is known to transmit dna damage signals through the atrchk1 kinase cascade, whether posttranslational modifications other than phosphorylation are important for this pathway remains largely unknown. When you save presentation as a pdf file it freezes the formatting and layout. Sumoylation of alphatubulin has been confirmed in vitro, while betatubulin has been identified as a putative sumo1 and sumo3 target 19. Like ubiquitin, sumo has been found to be covalently attached to certain lysine residues of specific target proteins. Sumoylation and ubiquitylation circuitry controls pregnane. Interplay between phosphorylation and sumoylation events determines cesta protein fate in brassinosteroid signalling. Small ubiquitinlike modifier sumo 1 is a protein of 97 amino acids that is structurally similar to ubiquitin and has been called by other names including smt3p, pmt2p, pic1, gmp1, ubl1, and sentrin.