scholarly journals The Membrane Associated RING-CH Proteins: A Family of E3 Ligases with Diverse Roles through the Cell

2014 ◽  
Vol 2014 ◽  
pp. 1-23 ◽  
Author(s):  
Tasleem Samji ◽  
Soonwook Hong ◽  
Robert E. Means
Keyword(s):  
Signal Transduction ◽  
Dna Repair ◽  
Essential Role ◽  
Proteolytic Degradation ◽  
Diverse Range ◽  
E3 Ligases ◽  
Cellular Processes ◽  
Range Of Functions ◽  
Membrane Bound ◽  
Lines Of Evidence

Since the discovery that conjugation of ubiquitin to proteins can drive proteolytic degradation, ubiquitination has been shown to perform a diverse range of functions in the cell. It plays an important role in endocytosis, signal transduction, trafficking of vesicles inside the cell, and even DNA repair. The process of ubiquitination-mediated control has turned out to be remarkably complex, involving a diverse array of proteins and many levels of control. This review focuses on a family of structurally related E3 ligases termed the membrane-associated RING-CH (MARCH) ubiquitin ligases, which were originally discovered as structural homologs to the virals E3s, K3, and K5 from Kaposi’s sarcoma-associated herpesvirus (KSHV). These proteins contain a catalytic RING-CH finger and are typically membrane-bound, with some having up to 14 putative transmembrane domains. Despite several lines of evidence showing that the MARCH proteins play a complex and essential role in several cellular processes, this family remains understudied.

Snake Venom Disintegrins: An Overview of their Interaction with Integrins

2019 ◽  
Vol 20 (4) ◽  
pp. 465-477 ◽  
Author(s):  
Pedro Henrique Souza Cesar ◽  
Mariana Aparecida Braga ◽  
Marcus Vinicius Cardoso Trento ◽  
Danilo Luccas Menaldo ◽  
Silvana Marcussi
Keyword(s):  
Signal Transduction ◽  
Cell Surface ◽  
Essential Role ◽  
Antitumor Agents ◽  
Structural Models ◽  
New Drugs ◽  
Snake Venoms ◽  
Cellular Processes ◽  
Pharmacological Potential ◽  
Direct Use

Disintegrins are non-enzymatic proteins that interfere on cell–cell interactions and signal transduction, contributing to the toxicity of snake venoms and play an essential role in envenomations. Most of their pharmacological and toxic effects are the result of the interaction of these molecules with cell surface ligands, which has been widely described and studied. These proteins may act on platelets, leading to hemorrhage, and may also induce apoptosis and cytotoxicity, which highlights a high pharmacological potential for the development of thrombolytic and antitumor agents. Additionally, these molecules interfere with the functions of integrins by altering various cellular processes such as migration, adhesion and proliferation. This review gathers information on functional characteristics of disintegrins isolated from snake venoms, emphasizing a comprehensive view of the possibility of direct use of these molecules in the development of new drugs, or even indirectly as structural models.

scholarly journals Distribution of disease-causing germline mutations in coiled-coils suggests essential role of their N-terminal region

2020 ◽  
Author(s):  
Zsofia E. Kalman ◽  
Bálint Mészáros ◽  
Zoltán Gáspári ◽  
Laszlo Dobson
Keyword(s):  
Essential Role ◽  
Coiled Coil ◽  
Germline Mutations ◽  
Coiled Coils ◽  
Helical Structures ◽  
Diverse Range ◽  
Human Proteins ◽  
Range Of Functions ◽  
Functional Explanations

AbstractNext-generation sequencing resulted in the identification of a huge number of naturally occurring variations in human proteins. The correct interpretation of the functional effects of these variations necessitates the understanding of how they modulate protein structure. Coiled-coils are α-helical structures responsible for a diverse range of functions, but most importantly, they facilitate the structural organization of macromolecular scaffolds via oligomerization. In this study, we analyzed a comprehensive set of disease-associated germline mutations in coiled-coil structures. Our results highlight the essential role of residues near the N-terminal part of coiled-coil regions, possibly critical for superhelix assembly and folding in some cases. We also show that coiled-coils of different oligomerization states exhibit characteristically distinct patterns of disease-causing mutations. Our study provides structural and functional explanations on how disease emerges through the mutation of these structural motifs.

Some Aspects of the Polyhexamethyleneguanidine Salts Effect on Cell Cultures

2014 ◽  
Vol 1 (1) ◽  
pp. 62-67 ◽  
Author(s):  
M. Mandygra ◽  
A. Lysytsia
Keyword(s):  
Proliferative Activity ◽  
Cell Monolayer ◽  
Eukaryotic Cell ◽  
Culture Methods ◽  
Cellular Processes ◽  
Negative Effect ◽  
Membrane Bound ◽  
Membrane Bound Enzymes ◽  
Anion Type ◽  
Cell Culture Methods

Aim. To investigate the effect of polyhexamethyleneguanidine (PHMG) to eukaryotic cell culture. Methods. The passaged bovine tracheal cells culture (TCC) and primary culture of chicken embryo fi broblasts (FCE) were used in the experiments. TCC and FCE monolayers were treated with aqueous solutions of PHMG chloride or succinate. The method of PHMG polycation adsorption to the cells’ plasma membrane together with microscopy were applied. Results. The dependence of PHMG effect on the eukaryotic cells on the agent concentration, duration of exposure and the anion type has been fi xed. The PHMG concentration of 10 –5 per cent (0.1 μg/ml) never causes degradation of the previously formed cell monolayer, while the higher concentrations damage it. The conditions of the PHMG chloride and succinate’s negative effect on cell proliferation and inhibition of monolayer formation were determined. The hypothesis that under certain conditions PHMG stimulates the proliferative activity of the cells has been confi rmed. Stimulation may be associated with non-specifi c stress adaptation of cells. In this case, it is due to modifi cations of the cell membrane after PHMG adsorption to it. Conclusions. PHMG polycation binds with the membrane’s phosphoglycerides fi rmly and irreversibly. A portion of the lipids are removed from participation in the normal cellular processes at that. At the same time, the synthesis of new lipids and membrane-bound enzymes is probably accelerated. The phospholip ids’ neogenesis acceleration can stimulate mitosis under certain conditions. The obtained results can be used in the biotechnologies.

scholarly journals The Multifaceted Roles of USP15 in Signal Transduction

2021 ◽  
Vol 22 (9) ◽  
pp. 4728
Author(s):  
Tanuza Das ◽  
Eun Joo Song ◽  
Eunice EunKyeong Kim
Keyword(s):  
Signal Transduction ◽  
Signaling Pathways ◽  
Cellular Networks ◽  
Clinical Applications ◽  
Regulatory Mechanisms ◽  
Signaling Networks ◽  
Post Translational Modification ◽  
Comprehensive Overview ◽  
E3 Ligases ◽  
Disease Markers

Ubiquitination and deubiquitination are protein post-translational modification processes that have been recognized as crucial mediators of many complex cellular networks, including maintaining ubiquitin homeostasis, controlling protein stability, and regulating several signaling pathways. Therefore, some of the enzymes involved in ubiquitination and deubiquitination, particularly E3 ligases and deubiquitinases, have attracted attention for drug discovery. Here, we review recent findings on USP15, one of the deubiquitinases, which regulates diverse signaling pathways by deubiquitinating vital target proteins. Even though several basic previous studies have uncovered the versatile roles of USP15 in different signaling networks, those have not yet been systematically and specifically reviewed, which can provide important information about possible disease markers and clinical applications. This review will provide a comprehensive overview of our current understanding of the regulatory mechanisms of USP15 on different signaling pathways for which dynamic reverse ubiquitination is a key regulator.

scholarly journals Targeting DNA Repair and Chromatin Crosstalk in Cancer Therapy

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 381
Author(s):  
Danielle P. Johnson ◽  
Mahesh B. Chandrasekharan ◽  
Marie Dutreix ◽  
Srividya Bhaskara
Keyword(s):  
Dna Repair ◽  
Cancer Therapy ◽  
Therapeutic Intervention ◽  
Synthetic Lethality ◽  
Checkpoint Proteins ◽  
Cellular Processes ◽  
Repair Pathways ◽  
Made In

Aberrant DNA repair pathways that underlie developmental diseases and cancers are potential targets for therapeutic intervention. Targeting DNA repair signal effectors, modulators and checkpoint proteins, and utilizing the synthetic lethality phenomena has led to seminal discoveries. Efforts to efficiently translate the basic findings to the clinic are currently underway. Chromatin modulation is an integral part of DNA repair cascades and an emerging field of investigation. Here, we discuss some of the key advancements made in DNA repair-based therapeutics and what is known regarding crosstalk between chromatin and repair pathways during various cellular processes, with an emphasis on cancer.

scholarly journals Crosstalk between Different DNA Repair Pathways Contributes to Neurodegenerative Diseases

Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 163
Author(s):  
Swapnil Gupta ◽  
Panpan You ◽  
Tanima SenGupta ◽  
Hilde Nilsen ◽  
Kulbhushan Sharma
Keyword(s):  
Dna Repair ◽  
Neurodegenerative Diseases ◽  
3D Models ◽  
Model Systems ◽  
Spinocerebellar Ataxias ◽  
C Elegans ◽  
Cellular Processes ◽  
Age Related ◽  
Damage Response ◽  
Lateral Sclerosis

Genomic integrity is maintained by DNA repair and the DNA damage response (DDR). Defects in certain DNA repair genes give rise to many rare progressive neurodegenerative diseases (NDDs), such as ocular motor ataxia, Huntington disease (HD), and spinocerebellar ataxias (SCA). Dysregulation or dysfunction of DDR is also proposed to contribute to more common NDDs, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and Amyotrophic Lateral Sclerosis (ALS). Here, we present mechanisms that link DDR with neurodegeneration in rare NDDs caused by defects in the DDR and discuss the relevance for more common age-related neurodegenerative diseases. Moreover, we highlight recent insight into the crosstalk between the DDR and other cellular processes known to be disturbed during NDDs. We compare the strengths and limitations of established model systems to model human NDDs, ranging from C. elegans and mouse models towards advanced stem cell-based 3D models.

GSK-3 Inhibitors in Regulation and Controlling of Colon Carcinoma

2021 ◽  
Vol 22 ◽  
Author(s):  
Sitansu Sekhar Nanda ◽  
Md Imran Hossain ◽  
Heongkyu Ju ◽  
Dong Kee Yi
Keyword(s):  
Colon Carcinoma ◽  
Clinical Studies ◽  
Glycogen Synthesis ◽  
Morphological Examination ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Cellular Processes ◽  
Adenocarcinoma Cells ◽  
Membrane Bound

Background: GSK-3 inhibitors became a novel therapeutic agent treating cancer. There are so many uses of GSK-3 inhibitor for treating cancer like breast cancer, lung cancer, gastric cancer, and no pathological changes are shown by the morphological examination of GSK-3. Objectives: This review describes the recent affairs using GSK-3 inhibitors, mainly treating in colon carcinoma. The authorsAuthors have also shown the different mechanisms of different GSK-3 inhibitors for treating various cancers and proposed some mechanisms that can be useful for further research by GSK-3 inhibitors for various cancerscancer including colon carcinoma. Results: The majority of the cancers and pre-cancerous lesions are stimulated by the transformation of membrane-bound arachidonic acid (AA) to eicosanoids for the viability, proliferation, and spread of cancer. GSK-3 inhibitors can reinstate hostility to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) responsiveness in gastric adenocarcinoma cells. GSK-3, the final enzyme in glycogen synthesis, is a serine/threonine kinase that phosphorylates varied sequences that are more than a hundred in number, within proteins in an array of heterogeneous pathways. It is an essential module of an exceptionally huge number of cellular processes, a fundamental role in many metabolic processes and diseases. Many patients achieve long term remission with outstanding survival diagnosed with colon cancer through it. Conclusion: Before the extensive application of these proposed mechanisms of GSK-3 inhibitor, further evaluation and clinical studies are needed. After doing the appropriate clinical studies and morphological examination, it can be appropriate for extensive application.

scholarly journals Hanks-Type Serine/Threonine Protein Kinases and Phosphatases in Bacteria: Roles in Signaling and Adaptation to Various Environments

2018 ◽  
Vol 19 (10) ◽  
pp. 2872 ◽  
Author(s):  
Monika Janczarek ◽  
José-María Vinardell ◽  
Paulina Lipa ◽  
Magdalena Karaś
Keyword(s):  
Dna Binding ◽  
Essential Role ◽  
Current Knowledge ◽  
Response Regulator ◽  
Protein Targets ◽  
Regulatory Pathways ◽  
Translational Machinery ◽  
Signaling Systems ◽  
Cellular Processes ◽  
Division Cell

Reversible phosphorylation is a key mechanism that regulates many cellular processes in prokaryotes and eukaryotes. In prokaryotes, signal transduction includes two-component signaling systems, which involve a membrane sensor histidine kinase and a cognate DNA-binding response regulator. Several recent studies indicate that alternative regulatory pathways controlled by Hanks-type serine/threonine kinases (STKs) and serine/threonine phosphatases (STPs) also play an essential role in regulation of many different processes in bacteria, such as growth and cell division, cell wall biosynthesis, sporulation, biofilm formation, stress response, metabolic and developmental processes, as well as interactions (either pathogenic or symbiotic) with higher host organisms. Since these enzymes are not DNA-binding proteins, they exert the regulatory role via post-translational modifications of their protein targets. In this review, we summarize the current knowledge of STKs and STPs, and discuss how these enzymes mediate gene expression in prokaryotes. Many studies indicate that regulatory systems based on Hanks-type STKs and STPs play an essential role in the regulation of various cellular processes, by reversibly phosphorylating many protein targets, among them several regulatory proteins of other signaling cascades. These data show high complexity of bacterial regulatory network, in which the crosstalk between STK/STP signaling enzymes, components of TCSs, and the translational machinery occurs. In this regulation, the STK/STP systems have been proved to play important roles.

scholarly journals Aberrant Expression of Proteins Involved in Signal Transduction and DNA Repair Pathways in Lung Cancer and Their Association with Clinical Parameters

PLoS ONE ◽  
2012 ◽  
Vol 7 (2) ◽  
pp. e31087 ◽  
Author(s):  
Yong He ◽  
Zhen Zhou ◽  
Wayne L. Hofstetter ◽  
Yanbin Zhou ◽  
Wenxian Hu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Signal Transduction ◽  
Dna Repair ◽  
Clinical Parameters ◽  
Aberrant Expression ◽  
Repair Pathways
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