Special Issue "Protein SUMOylation"

Guest Editor
Prof. Dr. Seth Blackshaw
The Solomon H. Snyder Department of Neuroscience, School of Medicine, Johns Hopkins University, 329 Broadway Research Building, 725 North Wolfe St., Baltimore, MD 21205, USA
Website: http://neuroscience.jhu.edu/SethBlackshaw.php
E-Mail: sblack@jhmi.edu
Phone: +1 443 287 5609
Fax: +1 410 614 9568
Interests: transcriptional control of neural and glial development; protein SUMOylation; noncoding RNAs; functional proteomics; chronobiology

Dear Colleagues,

SUMOylation has emerged as a reversible and widely used means of modulating the activity and localization of many different classes of protein. Originally thought to primarily regulate nuclear processes such as transcription and DNA repair, recent work has revealed that SUMOylation plays a critical role in such diverse functions as regulating kinase and G-protein activity, cytoskeletal structure and ion channel function. It is now appreciated that site-specific SUMOylation guides cellular differentiation, regulates neuronal activity, and is misregulated in a range of human diseases. This issue intends to both review recent findings and to showcase original research in this fast moving field.

We thus invite submission of research and review manuscripts that cover any aspect of the biochemistry, cell biology, genetics or pharmacology of SUMO, SUMOylation enzymes and their cellular substrates and effector molecules. Areas of particular interest include, but are not limited to, advances in SUMOylation-dependent regulation of transcription factor activity and chromatin structure, dynamic regulation of SUMOylation by intracellular signaling, novel functional classes of proteins regulated by SUMOylation, and the role of SUMOylation in embryonic development, cancer and neurodegeneration. Other potential topics include the biology of the growing number of E3 SUMO ligases, SUMO binding proteins, and new genetic and pharmacological techniques for modulating protein SUMOylation in vivo.

We look forward to reading your contributions,

Prof. Dr. Seth Blackshaw
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed Open Access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. For the first couple of issues the Article Processing Charge (APC) will be waived for well-prepared manuscripts. English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.

• SUMO and SUMOylation
• cytoskeleton
• neurodegeneration
• development and differentiation
• ion channel and synapse
• proteomics cell dynamics
• Transcription and gene expression
• protein transport stability and structure
• ubiquitin, acetylation,  phosphorylation, and post-translational modification
• protease
• chromatin and epigenetics
• signal transduction

Type of Paper: Review
Title: Post Translational Modifications of the Progesterone Receptors
Authors: Hany A. Abdel-Hafiz and Kathryn B. Horwitz
Affiliation: Department of Medicine, Division of Endocrinology, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado 80045; E-Mail: Hany.Abdel-Hafiz@ucdenver.edu (H.A.A.-H.)
Abstract: Progesterone plays a key role in the development, differentiation and maintenance of female reproductive tissue. Depending on the cell, hormonal environment, growth condition, and developmental stage, progesterone can either stimulate cell proliferation or inhibit growth and promote differentiation. Progesterone receptors belong to the steroid hormone receptor superfamily of ligand dependent transcription factors.  Posttranslational modifications (PTMs) such as phosphorylation, acetylation, ubiquitination and SUMOylation have been shown to play an important role in transcriptional regulation of nuclear receptors and provide an added complexity to NR action. PTMs are important tools that cells use to control the function of proteins by regulating their activity, stability, subcellular localization, protein-protein interaction and provide potential mechanisms for cell-or gene specific regulation. Our understanding of the impact of these PTMs on the function of PRs will help in the identification of chemotherapeutic agents for breast cancer treatment. In this review we discuss the effect of PTMs on PRs function and its implication in breast cancer treatment.

Type of Paper: Review
Title: Sumoylation at the Host-Pathogen Interface
Author: Van G. Wilson
Affiliation: Department of Microbial and Molecular Pathogenesis, College of Medicine, Texas A & M University System Health Science Center, College Station, Bryan, TX  77807-1359, USA; E-Mail: WILSON@medicine.tamhsc.edu
Abstract: Many viral proteins have been shown to be sumoylated with corresponding regulatory effects on their protein function, indicating that this host cell modification process is widely exploited by viral pathogens to control viral activity.  In addition to using sumoylation to regulate their own proteins, several viral pathogens have been shown to modulate overall host sumoylation levels. Given the large number of cellular targets for SUMO addition and the breadth of critical cellular processes that are regulated via sumoylation, viral modulation of overall sumoylation presumably alters the cellular environment to ensure that it is favorable for viral reproduction and/or persistence.  Like some viruses, certain bacterial plant pathogens also target the sumoylation system, usually decreasing sumoylation to disrupt host anti-pathogen responses. The recent demonstration that Listeria monocytogenes also disrupts host sumoylation, and that this is required for efficient infection, extends the plant pathogen observations to a human pathogen and suggests that pathogen modulation of host sumoylation may be more widespread than previously appreciated. This review will focus on recent aspects of how pathogens modulate the host sumoylation system and how this benefits the pathogen.

Type of Paper: Review
Title: Sumoylation in Drosophila Development
Author: Albert J. Courey
Affiliation: Department of Chemistry and Biochemistry, UCLA, Los Angeles, CA 90095, USA; E-Mail: courey@chem.ucla.edu
Abstract: Post-translational covalent conjugation of proteins to SUMO (small ubiquitin-like modifier) is widespread in eukaryotic biology. Numerous system-wide and protein-specific studies have revealed a requirement for SUMO in a variety of cellular and developmental processes, including embryonic pattern formation, cell-cycle regulation, and signal transduction. The involvement of the SUMO pathway in such a wide range of biological functions stems from the diverse effects of sumoylation on target protein function, including effects on intracellular targeting, protein stability, protein-protein interactions, and protein conformation. Significant insight into the in vivo role of sumoylation has been provided by studies in Drosophila that utilize genetic manipulation and SUMO proteomic analysis. This review discusses our current understanding of the diverse roles for SUMO in Drosophila development.

Type of Paper: Review
Title: SUMO Wrestling Recombination
Author: Lumir Krejci
Affiliation: Wellcome International Senior Research Fellow, National Centre for Biomolecular Research, and Department of Biology, Masaryk University, Kamenice 5/A4, Brno 625 00, Czech Republic; E-Mail: lkrejci@chemi.muni.cz
Abstract: Homologous recombination (HR) serves as an important pathway for error-free repair of DNA double-strand breaks (DSBs) resulting from replication fork collapse or damaged DNA by endogeneous or exogeneous agents. The failure to repair DSBs has detrimental consequences to the cells. The mechanism of HR comprises multi-step process involving DNA homology search and strand invasion to form a joint molecules between the recombining homologous DNA molecules followed by DNA synthesis and resolution. The HR mechanism proceeds through a series of reversible intermediates that have to be under tight regulation allowing the flexibility of recombination outcomes. In recent years, the increasing evidences suggest that SUMOylation can significantly influence HR and could represent one of the key regulatory components. The subset of HR proteins (such as Rad52, Rad59, RPA or Srs2) was found to be SUMOylated or interact with SUMO machinery (Rad51 recombinase). The specific effects of SUMOylation on the activities and dynamics of HR proteins will be addressed. SUMOylation has been also shown to play an important role in regulation of HR at ribosomal and telomeric DNA, during meiosis and replication-associated DNA repair processes. In particular, we will point out role of Smc5-Smc6 complex, Zip3 and Red1, and the interesting interplay between SUMO and ubiquitin modification of proliferating cell nuclear antigen (PCNA), which can regulate the error-free repair of damaged DNA or restart of blocked forks during replication. The boom in the field of SUMOylation in the recent years shows its comprehensive role during many recombination events in the cells. The detail understanding of molecular mechanism and the effects of SUMO modifications in the regulation of HR will be main research focus in this decade.

Type of Paper: Review
Title: DeSUMOylation Controls Insulin Exocytosis in Response to Metabolic Signals
Author: Elisa Vergari, XiaoQing Dai and Patrick E. MacDonald
Affiliation: Alberta Diabetes Institute and Department of Pharmacology, University of Alberta, Edmonton, Canada; E-Mail: pmacdonald@pmcol.ualberta.ca
Abstract: The secretion of insulin by pancreatic b-cells plays a pivotal role in glucose homeostasis and diabetes. SUMOylation might represent a novel and important mechanism regulating insulin secretion. While the control of b-cell transcription factors such as Pdx1 and MafA has been suggested, SUMOylation may also modulate the ion-channels and exocytotic mechanisms that mediate insulin release. Recent work implicates SUMO1 in the control of insulin exocytosis in rodents and humans. The SUMO-specific proteases (SENPs) both process the pre-forms of SUMO to their mature forms and cleave SUMO from modified substrates. SENP1, 2 and 6 are expressed in pancreatic b-cells. SUMO1 inhibits glucose dependent insulin release, while SENP1, acting in a glucose-dependent manner, is proposed to enhance insulin exocytosis by deSUMOylating the exocytotic Ca²⁺ sensor synaptotagmnin VII. The regulation of deSUMOylation by glucose may result from changes in cellular redox status and NADPH generation, both proposed as major metabolic coupling factors for insulin release. Indeed, we show SENP1 mediates the amplifying effect of NADPH on b-cell exocytosis, and the ability of SENP1 to affect insulin exocytosis is dramatically altered by cellular redox state. Taken together, we suggest that deSUMOylation at the site of exocytosis, mediated by SENP1 in response to metabolic signals, acts to amplify b-cells exocytotic responses and insulin secretion, suggesting an important role for acute (de)SUMOylation in insulin secretion.