The GCN5: its biological functions and therapeutic potentials

2021 ◽  
Vol 135 (1) ◽  
pp. 231-257
Author(s):  
Md. Ezazul Haque ◽  
Md. Jakaria ◽  
Mahbuba Akther ◽  
Duk-Yeon Cho ◽  
In-Su Kim ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Cellular Proliferation ◽  
Chromatin Modification ◽  
Structural Features ◽  
Histone Acetyltransferases ◽  
Epigenetic Landscape ◽  
General Control ◽  
Wide Range ◽  
Lysine Acetyltransferase

Abstract General control non-depressible 5 (GCN5) or lysine acetyltransferase 2A (KAT2A) is one of the most highly studied histone acetyltransferases. It acts as both histone acetyltransferase (HAT) and lysine acetyltransferase (KAT). As an HAT it plays a pivotal role in the epigenetic landscape and chromatin modification. Besides, GCN5 regulates a wide range of biological events such as gene regulation, cellular proliferation, metabolism and inflammation. Imbalance in the GCN5 activity has been reported in many disorders such as cancer, metabolic disorders, autoimmune disorders and neurological disorders. Therefore, unravelling the role of GCN5 in different diseases progression is a prerequisite for both understanding and developing novel therapeutic agents of these diseases. In this review, we have discussed the structural features, the biological function of GCN5 and the mechanical link with the diseases associated with its imbalance. Moreover, the present GCN5 modulators and their limitations will be presented in a medicinal chemistry perspective.

The Jumonji family: past, present and future of histone demethylases in cancer

2014 ◽  
Vol 5 (3) ◽  
pp. 209-224 ◽  
Author(s):  
Gianluigi Franci ◽  
Alfonso Ciotta ◽  
Lucia Altucci
Keyword(s):  
Cardiac Disease ◽  
Neurological Disorders ◽  
Recent Literature ◽  
Tube Formation ◽  
Histone Demethylases ◽  
Post Translational Modifications ◽  
Biological Features ◽  
Wide Range ◽  
Expression Modulation

AbstractThe first Jumonji gene was cloned in 1995 by Takeuchi et al. [Takeuchi T, Yamazaki Y, Katoh-Fukui Y, Tsuchiya R, Kondo S, Motoyama J, Higashinakagawa T. Gene trap capture of a novel mouse gene, jumonji, required for neural tube formation. Genes Dev 1995; 9: 1211–22.]. Several genes sharing similar biological features have since been discovered, and are currently grouped into the JMJ family. Interestingly, their deregulation has been associated with cardiac disease, obesity, neurological disorders and cancer. One of the mechanisms underlying their function is gene expression modulation via histone post-translational modifications (PTMs). Increasing evidence of Jumonji deregulation in tumours such as colon, prostate, haematological and breast cancer is continually emerging, hence the need to acquire a better understanding. The Genesapiens.org database of patient arrays allows target expression levels to be investigated in a wide range of cancers, corroborating and extending the role of the JMJ family. Here, we provide an overview of the expression profile and regulation of JMJ family members in cancer, examining the most recent literature in the light of analyses drawn from this database.

Patent spotlight: small-molecule lysine acetyltransferase inhibitors (KATi)

2020 ◽  
Vol 9 (1) ◽  
pp. 17-28 ◽  
Author(s):  
James AL Brown
Keyword(s):  
Small Molecule ◽  
Neurological Disorders ◽  
Histone Acetyltransferases ◽  
Genome Maintenance ◽  
Multiple Cancer ◽  
Disease Treatment ◽  
Drug Classes ◽  
Patent Landscape ◽  
Cancer Types ◽  
Lysine Acetyltransferase

Lysine (or histone) acetyltransferases plays a key role in genome maintenance and gene regulation and dysregulation of acetylation is a recognized feature of many diseases, including several cancers. Here, the patent landscape surrounding lysine acetyltransferase inhibitors (KATi or HATi), with a focus on small-molecule compounds, is outlined and assessed. Overall, the 36 KATi-specific patents found were categorized into two distinct groups: specific small-molecule inhibitors (compounds and molecules) and patents applying KATi for targeted disease treatment. These patents recognize the emergent potential of KATi to significantly impact on the management of many diseases (including multiple cancer types, neurological disorders and immunological syndromes), improving the range of treatments (and drug classes) available for personalized medicine.

scholarly journals Human Parvoviruses May Affect the Development and Clinical Course of Meningitis and Meningoencephalitis

2020 ◽  
Vol 10 (6) ◽  
pp. 339
Author(s):  
Anda Vilmane ◽  
Anna Terentjeva ◽  
Paulius L. Tamosiunas ◽  
Normunds Suna ◽  
Inga Suna ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Clinical Course ◽  
Inflammatory Diseases ◽  
Parvovirus B19 ◽  
Clinical Manifestations ◽  
Human Parvovirus B19 ◽  
Routine Diagnostics ◽  
Wide Range ◽  
Infection Markers

Meningitis and meningoencephalitis are neurological inflammatory diseases, and although routine diagnostics include testing of a wide range of pathogens, still in many cases, no causative agent is detected. Human parvovirus B19 (B19V), human bocaviruses 1–4 (HBoV1–4), and human parvovirus 4 (hPARV4) are members of the Parvoviridae family and are associated with a wide range of clinical manifestations including neurological disorders. The main aim of this study was to determine whether human parvoviruses infection markers are present among patients with meningitis/meningoencephalitis in Latvia as well as to clarify the role of these viruses on the clinical course of the mentioned diseases. Our study revealed HBoV1–4 and B19V genomic sequences in 52.38% and 16.67% of patients, respectively. Furthermore, symptoms such as the presence of a headache and its severity, fatigue, disorientation, and difficulties to concentrate were significantly frequently present in patients with active parvovirus infection in comparison with parvoviruses negative patients, therefore we suggest that HBoV1–4 and B19V infection should be included in the diagnostics to reduce the number of meningitis/meningoencephalitis with unknown/unexplained etiology.

scholarly journals The Role of LncRNAs in Translation

2021 ◽  
Vol 7 (1) ◽  
pp. 16
Author(s):  
Didem Karakas ◽  
Bulent Ozpolat
Keyword(s):  
Transcriptional Activation ◽  
Chromatin Modification ◽  
Protein Translation ◽  
Cellular Functions ◽  
Protein Coding ◽  
Regulate Gene Expression ◽  
Translational Machinery ◽  
Wide Range ◽  
Non Coding Rnas

Long non-coding RNAs (lncRNAs), a group of non-protein coding RNAs with lengths of more than 200 nucleotides, exert their effects by binding to DNA, mRNA, microRNA, and proteins and regulate gene expression at the transcriptional, post-transcriptional, translational, and post-translational levels. Depending on cellular location, lncRNAs are involved in a wide range of cellular functions, including chromatin modification, transcriptional activation, transcriptional interference, scaffolding and regulation of translational machinery. This review highlights recent studies on lncRNAs in the regulation of protein translation by modulating the translational factors (i.e, eIF4E, eIF4G, eIF4A, 4E-BP1, eEF5A) and signaling pathways involved in this process as wells as their potential roles as tumor suppressors or tumor promoters.

scholarly journals R-Loops and Its Chro-Mates: The Strange Case of Dr. Jekyll and Mr. Hyde

2021 ◽  
Vol 22 (16) ◽  
pp. 8850
Author(s):  
Sidrit Uruci ◽  
Calvin Shun Yu Lo ◽  
David Wheeler ◽  
Nitika Taneja
Keyword(s):  
Replication Fork ◽  
Potential Role ◽  
Genome Instability ◽  
Chromatin Modification ◽  
Therapeutic Interventions ◽  
Epigenetic Landscape ◽  
Physiological Processes ◽  
Stalled Fork ◽  
Chromatin Modifiers

Since their discovery, R-loops have been associated with both physiological and pathological functions that are conserved across species. R-loops are a source of replication stress and genome instability, as seen in neurodegenerative disorders and cancer. In response, cells have evolved pathways to prevent R-loop accumulation as well as to resolve them. A growing body of evidence correlates R-loop accumulation with changes in the epigenetic landscape. However, the role of chromatin modification and remodeling in R-loops homeostasis remains unclear. This review covers various mechanisms precluding R-loop accumulation and highlights the role of chromatin modifiers and remodelers in facilitating timely R-loop resolution. We also discuss the enigmatic role of RNA:DNA hybrids in facilitating DNA repair, epigenetic landscape and the potential role of replication fork preservation pathways, active fork stability and stalled fork protection pathways, in avoiding replication-transcription conflicts. Finally, we discuss the potential role of several Chro-Mates (chromatin modifiers and remodelers) in the likely differentiation between persistent/detrimental R-loops and transient/benign R-loops that assist in various physiological processes relevant for therapeutic interventions.

scholarly journals Role of Vacha (Acorus calamus Linn.) in Neurological and Metabolic Disorders: Evidence from Ethnopharmacology, Phytochemistry, Pharmacology and Clinical Study

2020 ◽  
Vol 9 (4) ◽  
pp. 1176 ◽  
Author(s):  
Vineet Sharma ◽  
Rohit Sharma ◽  
DevNath Singh Gautam ◽  
Kamil Kuca ◽  
Eugenie Nepovimova ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Metabolic Disorders ◽  
Literature Survey ◽  
Acorus Calamus ◽  
Extensive Literature ◽  
Compelling Evidence ◽  
Liver Disorders ◽  
Active Constituents ◽  
Wide Range

Vacha (Acorus calamus Linn. (Acoraceae)) is a traditional Indian medicinal herb, which is practiced to treat a wide range of health ailments, including neurological, gastrointestinal, respiratory, metabolic, kidney, and liver disorders. The purpose of this paper is to provide a comprehensive up-to-date report on its ethnomedicinal use, phytochemistry, and pharmacotherapeutic potential, while identifying potential areas for further research. To date, 145 constituents have been isolated from this herb and identified, including phenylpropanoids, sesquiterpenoids, and monoterpenes. Compelling evidence is suggestive of the biopotential of its various extracts and active constituents in several metabolic and neurological disorders, such as anticonvulsant, antidepressant, antihypertensive, anti-inflammatory, immunomodulatory, neuroprotective, cardioprotective, and anti-obesity effects. The present extensive literature survey is expected to provide insights into the involvement of several signaling pathways and oxidative mechanisms that can mitigate oxidative stress, and other indirect mechanisms modulated by active biomolecules of A. calamus to improve neurological and metabolic disorders.

Understanding Cytokines Part I: Physiology and Mechanism of Action

2000 ◽  
Vol 2 (1) ◽  
pp. 30-40 ◽  
Author(s):  
Elizabeth J. Corwin
Keyword(s):  
Mechanism Of Action ◽  
Cellular Proliferation ◽  
Psychological Symptoms ◽  
Chronic Illnesses ◽  
Intercellular Signaling ◽  
Wide Range ◽  
Health And Illness ◽  
Infection And Inflammation ◽  
Health And Disease

This is the first of a 2-part article on understanding cytokines. Cytokines are intercellular signaling proteins released from virtually all nucleated cells that influence growth and cellular proliferation in a wide range of tissues. Cytokines have immune modulating effects and are understood to control most of the physical and psychological symptoms associated with infection and inflammation. Cytokines also influence reproduction and bone remodeling. Dysregulation of the cytokine cellular system has significant implications in the development of a variety of illnesses, including most autoimmune disorders, many diseases of the cardiovascular system, osteoporosis, asthma, and depression. For nurses to be adequately informed when caring for clients with chronic illnesses and to be sufficiently knowledgeable when evaluating client outcomes, an understanding of the physiology of cytokines, the occurrences of dysregulation, and the role of cytokines in health and illness is essential. In Part I of this review, cytokine physiology is presented, with an emphasis on characteristics, categories, and mechanism of action. Specific instances of cytokine function in health and disease and implications for nursing research and practice are presented in Part II.

scholarly journals The Role of Hackers in Countering Surveillance and Promoting Democracy

2015 ◽  
Vol 3 (2) ◽  
pp. 77-87 ◽  
Author(s):  
Sebastian Kubitschko
Keyword(s):  
Qualitative Research ◽  
Structural Features ◽  
Anonymous Communication ◽  
Civil Society Organization ◽  
Media Technologies ◽  
Wide Range ◽  
Computer Club ◽  
Emerging Issues ◽  
Per Se

Practices related to media technologies and infrastructures (MTI) are an increasingly important part of democratic constellations in general and of surveillance tactics in particular. This article does not seek to discuss surveillance <em>per se</em>, but instead to open a new line of inquiry by presenting qualitative research on the Chaos Computer Club (CCC)—one of the world’s largest and Europe’s oldest hacker organizations. Despite the longstanding conception of hacking as infused with political significance, the scope and style of hackers’ engagement with emerging issues related to surveillance remains poorly understood. The rationale of this paper is to examine the CCC as a civil society organization that counter-acts contemporary assemblages of surveillance in two ways: first, by de-constructing existing technology and by supporting, building, maintaining and using alternative media technologies and infrastructures that enable more secure and anonymous communication; and second, by articulating their expertise related to contemporary MTI to a wide range of audiences, publics and actors. Highlighting the significance of “privacy” for the health of democracy, I argue that the hacker organization is co-determining “interstitial spaces within information processing practices” (Cohen, 2012, p. 1931), and by doing so is acting on indispensable structural features of contemporary democratic constellations.

scholarly journals RFX1: a promising therapeutic arsenal against cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Joby Issac ◽  
Pooja S. Raveendran ◽  
Ani V. Das
Keyword(s):  
Protein Interactions ◽  
Target Genes ◽  
Cellular Proliferation ◽  
Protein Protein Interactions ◽  
Oncogenic Potential ◽  
Cellular Processes ◽  
Wide Range ◽  
Induced Apoptosis ◽  
Pleiotropic Function

AbstractRegulatory factor X1 (RFX1) is an evolutionary conserved transcriptional factor that influences a wide range of cellular processes such as cell cycle, cell proliferation, differentiation, and apoptosis, by regulating a number of target genes that are involved in such processes. On a closer look, these target genes also play a key role in tumorigenesis and associated events. Such observations paved the way for further studies evaluating the role of RFX1 in cancer. These studies were indispensable due to the failure of conventional chemotherapeutic drugs to target key cellular hallmarks such as cancer stemness, cellular plasticity, enhanced drug efflux, de-regulated DNA repair machinery, and altered pathways evading apoptosis. In this review, we compile significant evidence for the tumor-suppressive activities of RFX1 while also analyzing its oncogenic potential in some cancers. RFX1 induction decreased cellular proliferation, modulated the immune system, induced apoptosis, reduced chemoresistance, and sensitized cancer stem cells for chemotherapy. Thus, our review discusses the pleiotropic function of RFX1 in multitudinous gene regulations, decisive protein–protein interactions, and also its role in regulating key cell signaling events in cancer. Elucidation of these regulatory mechanisms can be further utilized for RFX1 targeted therapy.

scholarly journals Tissue Hyperplasia and Enhanced T-Cell Signalling via ZAP-70 in c-Cbl-Deficient Mice

1998 ◽  
Vol 18 (8) ◽  
pp. 4872-4882 ◽  
Author(s):  
Maria A. Murphy ◽  
Ralf G. Schnall ◽  
Deon J. Venter ◽  
Louise Barnett ◽  
Ivan Bertoncello ◽  
...  
Keyword(s):  
T Cell ◽  
Cellular Proliferation ◽  
Biochemical Characterization ◽  
Cell Signalling ◽  
Control Cell ◽  
Receptor Expression ◽  
Negative Regulator ◽  
Wide Range ◽  
Deficient Mice

ABSTRACT The c-Cbl protein is tyrosine phosphorylated and forms complexes with a wide range of signalling partners in response to various growth factors. How c-Cbl interacts with proteins, such as Grb2, phosphatidylinositol 3-kinase, and phosphorylated receptors, is well understood, but its role in these complexes is unclear. Recently, theCaenorhabditis elegans Cbl homolog, Sli-1, was shown to act as a negative regulator of epidermal growth factor receptor signalling. This finding forced a reassessment of the role of Cbl proteins and highlighted the desirability of testing genetically whether c-Cbl acts as a negative regulator of mammalian signalling. Here we investigate the role of c-Cbl in development and homeostasis in mice by targeted disruption of the c-Cbl locus. c-Cbl-deficient mice were viable, fertile, and outwardly normal in appearance. Bone development and remodelling also appeared normal in c-Cbl mutants, despite a previously reported requirement for c-Cbl in osteoclast function. However, consistent with a high level of expression of c-Cbl in the hemopoietic compartment, c-Cbl-deficient mice displayed marked changes in their hemopoietic profiles, including altered T-cell receptor expression, lymphoid hyperplasia, and primary splenic extramedullary hemopoiesis. The mammary fat pads of mutant female mice also showed increased ductal density and branching compared to those of their wild-type littermates, indicating an unanticipated role for c-Cbl in regulating mammary growth. Collectively, the hyperplastic histological changes seen in c-Cbl mutant mice are indicative of a normal role for c-Cbl in negatively regulating signalling events that control cell growth. Consistent with this view, we observed greatly increased intracellular protein tyrosine phosphorylation in thymocytes following CD3ε cross-linking. In particular, phosphorylation of ZAP-70 kinase in thymocytes was uncoupled from a requirement for CD4-mediated Lck activation. This study provides the first biochemical characterization of any organism that is deficient in a member of this unique protein family. Our findings demonstrate critical roles for c-Cbl in hemopoiesis and in controlling cellular proliferation and signalling by the Syk/ZAP-70 family of protein kinases.

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