We applied this method to analyze the autosumoylation of the e1 enzyme in. Developmental profiles of sumoylation pathway proteins in. Genes cells 312, 789800 schiltz rl, mizzen ca, vassilev a, cook rg, allis cd, nakatani y 1999 overlapping but. Gestational trophoblastic disease gtd is a gathering of uncommon tumors that include unusual development of cells inside a ladys uterus.
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. You have also helped to develop and improve my presentation. Here we monitor the expression of key sumo pathway proteins and levels of substrate protein sumoylation in. 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. Sumo enzymatic cascade catalyzes the dynamic posttranslational modification process of sumoylation i. Conjugation of this modifier to a target protein results in the alteration of target protein function. 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.
Histone modification table cell signaling technology. Epiquik in vivo universal protein sumoylation assay kit. Myc is an oncogenic transcription factor frequently dysregulated in human cancer. Sumoylation of target proteins in vivo has been shown to cause a number of different outcomes, including altered localization and binding partners. Sumoylation plays critical roles during cell cycle progression. Like ubiquitin, sumo has been found to be covalently attached to certain lysine residues of specific target proteins. 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. Gtd does not create from cells of the uterus like cervical tumor or endometrial uterine coating malignancy do. The other major cytoskeletal protein targeted by sumos is tubulin. Sumoylation is a highly transient posttranslational protein modification. 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. Sumoylation regulates the functional properties of a large number of proteins and thereby plays a very important role in the normal functions of cells.
Several nuclear receptor nr superfamily members are known to be the molecular target of either the small ubiquitinrelated modifier sumo or ubiquitinsignaling pathways. 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. In many cases, sumoylation of transcriptional regulators correlates with inhibition of transcription. The modification involves the covalent attachment of a 12kda sumo small ubiquitinlike. Apr 08, 2010 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. Sep 25, 2014 myc oncogenic transcription factors cmyc, nmyc, and lmyc coordinate the control of cell growth, division, and metabolism. 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.
For plants, in particular, both genetic analyses and the rapid accumulation of. In addition, key factors controlling cellular senescence are known to be sumoylated. Sumoylationmediated regulation of cell cycle progression. Attachment of sumo to target proteins occurs via a number of specific activating and. From the evaluation, three thresholds with high, medium and low stringency were chosen for gpssumo. The identification of sumoylation sites and sumointeraction. Sumoylation stabilizes the association of the bromodomain with the chromatin modifiers, thus promoting the establishment of gene silencing. Sumoylation and ubiquitylation circuitry controls pregnane. Further supporting the importance of sumoylation are studies that have implicated a role for small ubiquitinlike modifier sumo modification in human diseases. In the publish as pdf or xps dialog box, choose a location to save the file to. Despite this, relatively little is known about the spatial and temporal regulation of proteins that mediate sumoylation and desumoylation in the cns. Sumo proteins are conjugated to a protein substrate, creating an interface for the recruitment of cofactors harboring sumointeracting motifs sims.
Sumoylation pathway is required to maintain the basal. Mapping of sumo sites and analysis of sumoylation changes. During infection, pathogenic bacteria manipulate the host cell in various ways to allow their own replication, propagation. The dynamic sumoylation pattern observed throughout the cell cycle is ensured via distinct spatial and temporal regulation of the sumo machinery. In contrast to ubiquitination, however, sumoylation does not promote. Desumoylation and aggregation are two crucial steps required for the translation of the mrna targets of cpeb3 and for dendritic filopodia formation. Sumoylation of cpeb3 is a constitutive, reversible process in the cell, mediating a physiological function. The cterminal region and sumoylation of cockayne syndrome. Sumoylation in cellular senescence and aging bentham science. 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.
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. Sumoylation is a reversible posttranslational modification that. The sumo e3 protein pias3 protein inhibitor of activated stat3 is upregulated in a number of different cancer. Covalent modification by sumo polypeptides, or sumoylation, is an important regulator of the functional properties of many proteins. The development of sumoylation inhibitorsa novel approach to. The molecular and biochemical mechanisms involved in sumoylation have been the subject of intense interest in recent years.
A posttranslational modification targeting cytoskeletal proteins related publications. The atr atm ataxia telangiectasiamutated and rad3related checkpoint is a crucial dna damage signaling pathway. Clarke as, lowell je, jacobson sj, pillus l 1999 esa1p is an essential histone acetyltransferase required for cell cycle progression. The role of sumoylation in the auxin response pathway. A chemical and enzymatic approach to study sitespecific. Sumoylation is an inhibitory constraint that regulates the. Sumoylation are important for the functions of csb in. Sumoylation of alphatubulin has been confirmed in vitro, while betatubulin has been identified as a putative sumo1 and sumo3 target 19. 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.
Pdf converter is a online webbased document to pdf converter software. Mapping both sumoconjugation sites and sims is required to study the. 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. Herein, we show that sumoylation of the tfap2a transcription factor is required to maintain the basal breast cancer phenotype. Download figure open in new tab download powerpoint. All the spaces, line breaks will be automatically removed. Convert and create pdf from various types of files like word doc, excel xls, powerpoint ppt. Inhibiting the sumoylation pathway may be an effective treatment strategy for basal breast cancer. 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. 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. Myc oncogenic transcription factors cmyc, nmyc, and lmyc coordinate the control of cell growth, division, and metabolism. 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. We show that sumo and ubiquitin circuitry coordinately modifies the pregnane x receptor pxr. Interplay between phosphorylation and sumoylation events determines cesta protein fate in brassinosteroid signalling.
Methods plasmids for the nterminal in situtap tag, a part of the tbsumo open reading frame orf was ampli. Save powerpoint presentations as pdf files office support. It is hypothesised that sumo contributes to the aggressive nature of breast cancer. Sumoylation and desumoylation at a glance journal of cell science. Numerous targets of the sumoylation pathway have been identified downstream from ube2i and pias1, specifically, stat family members, p53 and cjun. Lamoliatte et e a monoclonal antibody specific for sumo3 tryptic peptides to enhance proteomic. Small ubiquitinlike modifier proteins or sumo modify the function of protein substrates involved in various cellular processes including dna damage response ddr.
This volume, edited and written by leading international experts, is the first book to be devoted to sumoylation. Posttranslational modification by the small ubiquitinlike modifier sumo proteins, a process termed sumoylation, is involved in many fundamental cellular processes. Many important cell cycle regulators, including many oncogenes and tumor suppressors, are functionally regulated via sumoylation. Sumoylation is directed by an enzymatic cascade analogous to that involved in ubiquitination. Sumoylation in cellular senescence and aging research. Global protein sumoylation and expression of components in sumoylation pathway were recently found to be altered in the process of organismal aging. Sumoylation of atrip potentiates dna damage signaling by. However, little is currently known regarding how these two posttranslational modifications interact to control nr biology. Sumoylation promotes survival and integration of neural. It presents information on the history, evolution and mechanis. Sumoylation is an essential ubiquitin like modification involved in important biological processes in eukaryotic cells. Interactions in the human and plasmodium falciparum sumo conjugation. 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. Sumoylation pathway accessscience from mcgrawhill education.
This effect on sumoylation may support efficient infection by listeria. Download fulltext pdf download fulltext pdf pml, sumoylation, and senescence article pdf available in frontiers in oncology 3. It is becoming apparent that dysregulated sumo contribute to carcinogenesis by affecting posttranscriptional modification of key proteins. Interplay between phosphorylation and sumoylation events. The performance under these three thresholds was presented. Protein sumoylation regulates multiple processes involved in the differentiation and maturation of cells and tissues during development. 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. A proline90 residue unique to sumo4 prevents maturation and sumoylation. When you save presentation as a pdf file it freezes the formatting and layout. Sumoylation regulates lkb1 localization and its oncogenic. A sumoylationdependent transcriptional subprogram is. Thus, inhibition of sumoylation may merit investigation as a possible therapy for mycdriven human cancers. Download ppt lkb1 is an upstream activator of ampk promoting the phosphorylation of ampk thr172 in the.
Sumoylation in gene regulation and cardiac disease. Sumoylation and human disease pathogenesis sciencedirect. Protein sumoylation modification and its associations with disease. Small ubiquitinrelated modifier sumo is a protein moiety that is ligated to. Nov, 2014 protein sumoylation plays an important role in regulation of many cellular processes. After neuronal stimulation, cpeb3 becomes desumoylated and more aggregated. Sumoylation proteins in breast cancer springerlink. Sumoylation in cellular senescence and aging volume. Mycinduced sumoylation is a therapeutic vulnerability for. There are striking similarities between the machinery that attaches sumo to substrate proteins and the enzymes that participate in ubiquitination fig. The regulatory role of sumoylation, the attachment of a small ubiquitinrelated modifier to a target protein, has been. Protein sumoylation plays an important role in regulation of many cellular processes.
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. People can view the slides even if they dont have powerpoint, but they cant make changes to it. Gestational trophoplastic tumors list of high impact. The sumoylation pathway is dysregulated in multiple. Lkb1 sumoylation is augmented in preclinical mouse models and clinical hcc, being a hallmark of more aggressive hcc tumors. Sumoylation in neurodegenerative diseases abstract. Largescale analysis of lysine sumoylation by sumo remnant. For example, increased ubc9 levels are found in a number of human cancers, and ubc9 overexpression can increase cancer cell growth 25, 26. Structural analysis suggests that the phd finger and the bromodomain cooperate as an integrated unit to recruit ubc9 and facilitate sumoylation zeng et al.
Listeria monocytogenes impairs sumoylation for efficient. Sumoylation of ephb1 suppresses neuroblastoma tumorigenesis. Charts depicting the percentage of different types of proteins targeted for sumoylation as determined by proteomic analyses. 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. Sumoylation and desumoylation at a glance journal of. Our data suggest that pol2 sumoylation occurs during replication. Recent reports reveal two new examples of human disease. Small ubiquitinrelated modifier sumo proteins are members of ubiquitinlike superfamily proteins that can be covalently. Ulps are also required for generating mature sumo from the sumo precursor, which contains a short peptide blocking its c terminus.
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. Biochemical and biophysical research communications. 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. This poster article discusses the enzymes that mediate sumoylation and desumoylation, concentrating on their. The subsequent deconjugation of sumo from target proteins is conducted by a class of enzymes termed sumo proteases. Sumoylation is an essential ubiquitinlike modification involved in important biological processes in eukaryotic cells. Kimura a, horikoshi m 1998 tip60 acetylates six lysines of a specific class in core histones in vitro. Sumoylation is a posttranslational modification involved in various cellular processes, such as nuclearcytosolic transport, transcriptional regulation, apoptosis, protein stability, response to stress, and. Mar 11, 2009 covalent modification by sumo polypeptides, or sumoylation, is an important regulator of the functional properties of many proteins. 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. 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. Sumoylation at chromatin represses cell growth and.
588 1282 544 1482 946 1160 1297 891 1079 1337 972 692 1127 44 1467 83 664 616 1473 1338 906 323 1171 991 1061 142 933 83 346 1076