scholarly journals Open Biology: overview for special issue on dynamics of protein fatty acylation

Open Biology ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 210228
Author(s):  
Marilyn D. Resh
Keyword(s):  
Protein Modification ◽  
Egf Receptor ◽  
Immune Cell ◽  
Protein Localization ◽  
Intramolecular Interactions ◽  
Covalent Attachment ◽  
Signalling Pathways ◽  
Great Promise ◽  
Special Issue ◽  
Fatty Acylation

Fatty acylation is a widespread form of protein modification that occurs on specific intracellular and secreted proteins. Beyond increasing hydrophobicity and the affinity of the modified protein for lipid bilayers, covalent attachment of a fatty acid exerts effects on protein localization, inter- and intramolecular interactions and signal transduction. As such, research into protein fatty acylation has been embraced by an extensive community of biologists. This special issue highlights advances at the forefront of the field, by focusing on two families of enzymes that catalyse post-translational protein fatty acylation, zDHHC palmitoyl acyltransferases and membrane-bound O-acyl transferases, and signalling pathways regulated by their fatty acylated protein substrates. The collected contributions catalogue the tremendous progress that has been made in enzyme and substrate identification. In addition, articles in this special issue provide insights into the pivotal functions of fatty acylated proteins in immune cell, insulin and EGF receptor-mediated signalling pathways. As selective inhibitors of protein fatty acyltransferases are generated, the future holds great promise for therapeutic targeting of fatty acyltransferases that play key roles in human disease.

Site-Specific Protein Covalent Attachment to Nanotubes and Its Electronic Impact on Single Molecule Function

2019 ◽  
Author(s):  
Adam Beachey ◽  
Harley Worthy ◽  
William David Jamieson ◽  
Suzanne Thomas ◽  
Benjamin Bowen ◽  
...  
Keyword(s):  
Single Molecule ◽  
Fluorescent Protein ◽  
Functional Integration ◽  
Attachment Site ◽  
Covalent Attachment ◽  
Great Promise ◽  
Functional Coupling ◽  
Phenyl Azide ◽  
Electronic Impact ◽  
Protein Attachment

<p>Functional integration of proteins with carbon-based nanomaterials such as nanotubes holds great promise in emerging electronic and optoelectronic applications. Control over protein attachment poses a major challenge for consistent and useful device fabrication, especially when utilizing single/few molecule properties. Here, we exploit genetically encoded phenyl azide photochemistry to define the direct covalent attachment of three different proteins, including the fluorescent protein GFP, to carbon nanotube side walls. Single molecule fluorescence revealed that on attachment to SWCNTs GFP’s fluorescence changed in terms of intensity and improved resistance to photobleaching; essentially GFP is fluorescent for much longer on attachment. The site of attachment proved important in terms of electronic impact on GFP function, with the attachment site furthest from the functional center having the larger effect on fluorescence. Our approach provides a versatile and general method for generating intimate protein-CNT hybrid bioconjugates. It can be potentially applied easily to any protein of choice; attachment position and thus interface characteristics with the CNT can easily be changed by simply placing the phenyl azide chemistry at different residues by gene mutagenesis. Thus, our approach will allow consistent construction and modulate functional coupling through changing the protein attachment position.</p>

scholarly journals Platelets, immune cells and the coagulation cascade; friend or foe of the circulating tumour cell?

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Mark P. Ward ◽  
Laura E. Kane ◽  
Lucy A. Norris ◽  
Bashir M. Mohamed ◽  
Tanya Kelly ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Circulatory System ◽  
Morphological Characteristics ◽  
Metastatic Potential ◽  
Coagulation Cascade ◽  
Molecular Profile ◽  
Great Promise ◽  
Liquid Biopsies

AbstractCancer cells that transit from primary tumours into the circulatory system are known as circulating tumour cells (CTCs). These cancer cells have unique phenotypic and genotypic characteristics which allow them to survive within the circulation, subsequently extravasate and metastasise. CTCs have emerged as a useful diagnostic tool using “liquid biopsies” to report on the metastatic potential of cancers. However, CTCs by their nature interact with components of the blood circulatory system on a constant basis, influencing both their physical and morphological characteristics as well as metastatic capabilities. These properties and the associated molecular profile may provide critical diagnostic and prognostic capabilities in the clinic. Platelets interact with CTCs within minutes of their dissemination and are crucial in the formation of the initial metastatic niche. Platelets and coagulation proteins also alter the fate of a CTC by influencing EMT, promoting pro-survival signalling and aiding in evading immune cell destruction. CTCs have the capacity to directly hijack immune cells and utilise them to aid in CTC metastatic seeding processes. The disruption of CTC clusters may also offer a strategy for the treatment of advance staged cancers. Therapeutic disruption of these heterotypical interactions as well as direct CTC targeting hold great promise, especially with the advent of new immunotherapies and personalised medicines. Understanding the molecular role that platelets, immune cells and the coagulation cascade play in CTC biology will allow us to identify and characterise the most clinically relevant CTCs from patients. This will subsequently advance the clinical utility of CTCs in cancer diagnosis/prognosis.

scholarly journals Plasma Surface Engineering to Biofunctionalise Polymers for β-Cell Adhesion

Coatings ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1085
Author(s):  
Clara Tran ◽  
Nicole Hallahan ◽  
Elena Kosobrodova ◽  
Jason Tong ◽  
Peter Thorn ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Surface Engineering ◽  
Covalent Attachment ◽  
Great Promise ◽  
Β Cells ◽  
Β Cell ◽  
Surface Characterisation ◽  
Water Contact ◽  
Ecm Proteins ◽  
Aromatic Polymers

Implant devices containing insulin-secreting β-cells hold great promise for the treatment of diabetes. Using in vitro cell culture, long-term function and viability are enhanced when β-cells are cultured with extracellular matrix (ECM) proteins. Here, our goal is to engineer a favorable environment within implant devices, where ECM proteins are stably immobilized on polymer scaffolds, to better support β-cell adhesion. Four different polymer candidates (low-density polyethylene (LDPE), polystyrene (PS), polyethersulfone (PES) and polysulfone (PSU)) were treated using plasma immersion ion implantation (PIII) to enable the covalent attachment of laminin on their surfaces. Surface characterisation analysis shows the increased hydrophilicity, polar groups and radical density on all polymers after the treatment. Among the four polymers, PIII-treated LDPE has the highest water contact angle and the lowest radical density which correlate well with the non-significant protein binding improvement observed after 2 months of storage. The study found that the radical density created by PIII treatment of aromatic polymers was higher than that created by the treatment of aliphatic polymers. The higher radical density significantly improves laminin attachment to aromatic polymers, making them better substrates for β-cell adhesion.

scholarly journals Regulation of Energy Expenditure and Brown/Beige Thermogenic Activity by Interleukins: New Roles for Old Actors

2018 ◽  
Vol 19 (9) ◽  
pp. 2569 ◽  
Author(s):  
María García ◽  
Patricia Pazos ◽  
Luis Lima ◽  
Carlos Diéguez
Keyword(s):  
Energy Expenditure ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Molecular Switches ◽  
Metabolic Effects ◽  
Signalling Pathways ◽  
Functional Heterogeneity ◽  
Beige Adipocytes ◽  
The Central Nervous System ◽  
And Function

Obesity rates and the burden of metabolic associated diseases are escalating worldwide Energy burning brown and inducible beige adipocytes in human adipose tissues (ATs) have attracted considerable attention due to their therapeutic potential to counteract the deleterious metabolic effects of nutritional overload and overweight. Recent research has highlighted the relevance of resident and recruited ATs immune cell populations and their signalling mediators, cytokines, as modulators of the thermogenic activity of brown and beige ATs. In this review, we first provide an overview of the developmental, cellular and functional heterogeneity of the AT organ, as well as reported molecular switches of its heat-producing machinery. We also discuss the key contribution of various interleukins signalling pathways to energy and metabolic homeostasis and their roles in the biogenesis and function of brown and beige adipocytes. Besides local actions, attention is also drawn to their influence in the central nervous system (CNS) networks governing energy expenditure.

scholarly journals Development and retention of a primordial moonlighting pathway of protein modification in the absence of selection presents a puzzle

2018 ◽  
Vol 115 (4) ◽  
pp. 647-655 ◽  
Author(s):  
Xinyun Cao ◽  
Yaoqin Hong ◽  
Lei Zhu ◽  
Yuanyuan Hu ◽  
John E. Cronan
Keyword(s):  
Lipoic Acid ◽  
Protein Modification ◽  
Acid Synthesis ◽  
Covalent Attachment ◽  
Aquifex Aeolicus ◽  
Original Function ◽  
E Coli ◽  
Metabolism Enzymes ◽  
Glycine Cleavage ◽  
H Protein

Lipoic acid is synthesized by a remarkably atypical pathway in which the cofactor is assembled on its cognate proteins. An octanoyl moiety diverted from fatty acid synthesis is covalently attached to the acceptor protein, and sulfur insertion at carbons 6 and 8 of the octanoyl moiety form the lipoyl cofactor. Covalent attachment of this cofactor is required for function of several central metabolism enzymes, including the glycine cleavage H protein (GcvH). InBacillus subtilis, GcvH is the sole substrate for lipoate assembly. Hence lipoic acid-requiring 2-oxoacid dehydrogenase (OADH) proteins acquire the cofactor only by transfer from lipoylated GcvH. Lipoyl transfer has been argued to be the primordial pathway of OADH lipoylation. TheEscherichia colipathway where lipoate is directly assembled on both its GcvH and OADH proteins, is proposed to have arisen later. Because roughly 3 billion years separate the divergence of these bacteria, it is surprising thatE. coliGcvH functionally substitutes for theB. subtilisprotein in lipoyl transfer. Known and putative GcvHs from other bacteria and eukaryotes also substitute forB. subtilisGcvH in OADH modification. Because glycine cleavage is the primary GcvH role in ancestral bacteria that lack OADH enzymes, lipoyl transfer is a “moonlighting” function: that is, development of a new function while retaining the original function. This moonlighting has been conserved in the absence of selection by some, but not all, GcvH proteins. Moreover,Aquifex aeolicusencodes five putative GcvHs, two of which have the moonlighting function, whereas others function only in glycine cleavage.

Abstract P070: NEU3 Sialidase Overexpression Activates Cell Survival in Murine Skeletal Myoblasts C2C12 and Protects Them from Hypoxia

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Luigi Anastasia ◽  
Raffaella Scaringi ◽  
Nadia Papini ◽  
Andrea Garatti ◽  
Lorenzo Menicanti ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Egf Receptor ◽  
Day Treatment ◽  
Horse Serum ◽  
Critical Role ◽  
Cell Loss ◽  
Myoblast Differentiation ◽  
Signalling Pathways ◽  
Skeletal Myoblasts ◽  
Culturing Conditions

Membrane-bound sialidase NEU3 increase during skeletal muscle differentiation has been shown to protect myoblasts from apoptosis and drive the differentiation process [1]. Thus, the objective of this study was to assess whether up-regulation of NEU3 would enhance the ability of murine skeletal muscle cells to resist to hypoxia, ultimately opposing cell death. We found that C2C12 myoblasts overexpressing NEU3 (L-NEU3) became highly resistant to 1% oxygen or 200 mM deferoxamine induced hypoxia. Moreover, L-NEU3 myoblasts survived a seven-day treatment of combined hypoxia and low serum (2% horse serum used to induce myoblast differentiation), without any significant cell loss. On the contrary, wild type C2C12 could not resist to these culturing conditions and all died within 48h. Real Time PCR showed NEU3 expression increase during all hypoxic treatments both in C2C12 and L-NEU3 cells, suggesting an endogenous NEU3 activation under these conditions. Moreover, we found that NEU3 over-expression activated pro-survival signalling pathways through up-regulation and activation of EGF receptor. Overall, our data support the hypothesis that NEU3 may play a critical role in the response of skeletal myoblasts to hypoxia and the preservation of cell viability by activating pro-survival signalling pathways. [1] Anastasia L. et al. J.Biol.Chem. 2008, 283 (52): 36265–36271.

scholarly journals Recent Findings in the Posttranslational Modifications of PD-L1

2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Shu-Man Li ◽  
Jie Zhou ◽  
Yun Wang ◽  
Run-Cong Nie ◽  
Jie-Wei Chen ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Immune Checkpoint ◽  
Protein Modification ◽  
Immune Cell ◽  
Response Rate ◽  
Malignant Tumors ◽  
Objective Response ◽  
Cell Activity ◽  
Patients With Cancer ◽  
L1 Protein

Immune checkpoint therapy, such as the reactivation of T-cell activity by targeting programmed cell death 1 (PD-1) and its ligand PD-L1 (also called B7-H1 and CD274) has been found pivotal in changing the historically dim prognoses of malignant tumors by causing durable objective responses. However, the response rate of immune checkpoint therapy required huge improvements. It has been shown that the expression of PD-L1 on cancer cells and immune cell membranes is correlated with a more durable objective response rate to PD-L1 antibodies, which highlights the importance of deeply understanding how this protein is regulated. Posttranslational modifications such as phosphorylation, N-glycosylation, and ubiquitination of PD-L1 have emerged as important regulatory mechanisms that modulate immunosuppression in patients with cancer. In this review, we summarized the latest findings of PD-L1 protein modification and their clinical applications.

scholarly journals Mesenchymal Stem/Stromal Cells in Immunity and Disease: A Better Understanding for an Improved Use

2020 ◽  
Vol 9 (5) ◽  
pp. 1516 ◽  
Author(s):  
Makram Merimi ◽  
Laurence Lagneaux ◽  
Douâa Moussa Agha ◽  
Philippe Lewalle ◽  
Nathalie Meuleman ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Stromal Cells ◽  
State Of The Art ◽  
Basic Research ◽  
Research Articles ◽  
Great Promise ◽  
Special Issue ◽  
Tissue Microenvironment ◽  
Therapeutic Value ◽  
Immunomodulatory Properties

In this Special Issue, directed and supervised by Dr. Mehdi Najar, a collection of basic research articles and reviews, on the state of the art of Mesenchymal Stem/Stromal Cells (MSCs) immune biology, is presented. Among the major goals of this Special Issue is the presentation of an update about the immunomodulatory properties of MSCs and their capacity to respond to tissue microenvironment changes. MSCs hold great promise in the field of immunotherapy and regenerative medicine. Accordingly, a better understanding of MSC immune biology will improve their therapeutic value and use.

scholarly journals Obesity-associated cancer: an immunological perspective

2015 ◽  
Vol 75 (2) ◽  
pp. 125-138 ◽  
Author(s):  
Melissa J. Conroy ◽  
Margaret R. Dunne ◽  
Claire L. Donohoe ◽  
John V. Reynolds
Keyword(s):  
Immune Responses ◽  
Immune Cell ◽  
Inflammatory Cells ◽  
Epidemiological Studies ◽  
Signalling Pathways ◽  
Immune Balance ◽  
Immune Cell Subsets ◽  
Cancer Types ◽  
Endocrine Factors

Epidemiological studies have established an association between obesity, insulin resistance, type 2 diabetes and a number of cancer types. Research has focused predominantly on altered endocrine factors, growth factors and signalling pathways, with little known in man about the immune involvement in the relevant pathophysiological processes. Moreover, in an era of exciting new breakthroughs in cancer immunotherapy, there is also a need to study the safety and efficacy of immunotherapeutics in the complex setting of inflammatory-driven obesity-associated cancer. This review addresses key immune cell subsets underpinning obesity-associated inflammation and describes how such immune compartments might be targeted to prevent and treat obesity-associated cancer. We propose that the modulation, metabolism, migration and abundance of pro- and anti-inflammatory cells and tumour-specific T cells might be therapeutically altered to both restore immune balance, alleviating pathological inflammation, and to improve anti-tumour immune responses in obesity-associated cancer.

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