scholarly journals Strategies To Modulate Heritable Epigenetic Defects in Cellular Machinery: Lessons from Nature

2012 ◽  
Vol 6 (1) ◽  
pp. 1-24 ◽  
Author(s):  
Ganesh Pandian ◽  
Hiroshi Sugiyama
Keyword(s):  
Cellular Machinery ◽  
Epigenetic Defects

scholarly journals Nanoparticles as Drug Delivery Systems of RNAi in Cancer Therapy

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2380
Author(s):  
Diedie Li ◽  
Chengzhi Gao ◽  
Meiyan Kuang ◽  
Minhao Xu ◽  
Ben Wang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Therapeutic Strategy ◽  
Target Gene ◽  
Treatment Approach ◽  
Systemic Delivery ◽  
Efficient Delivery ◽  
Rnai Therapeutics ◽  
Cellular Machinery ◽  
Tumor Delivery

RNA interference (RNAi) can mediate gene-silencing by knocking down the expression of a target gene via cellular machinery with much higher efficiency in contrast to other antisense-based approaches which represents an emerging therapeutic strategy for combating cancer. Distinct characters of nanoparticles, such as distinctive size, are fundamental for the efficient delivery of RNAi therapeutics, allowing for higher targeting and safety. In this review, we present the mechanism of RNAi and briefly describe the hurdles and concerns of RNAi as a cancer treatment approach in systemic delivery. Furthermore, the current nanovectors for effective tumor delivery of RNAi therapeutics are classified, and the characteristics of different nanocarriers are summarized.

scholarly journals The Autophagy Machinery in Human-Parasitic Protists; Diverse Functions for Universally Conserved Proteins

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1258
Author(s):  
Hirokazu Sakamoto ◽  
Kumiko Nakada-Tsukui ◽  
Sébastien Besteiro
Keyword(s):  
Membrane Vesicle ◽  
Model Organisms ◽  
Unicellular Eukaryotes ◽  
Current State ◽  
Important Challenge ◽  
Molecular Machinery ◽  
Cellular Machinery ◽  
Apparent Reduction ◽  
Related Proteins ◽  
Genome Projects

Autophagy is a eukaryotic cellular machinery that is able to degrade large intracellular components, including organelles, and plays a pivotal role in cellular homeostasis. Target materials are enclosed by a double membrane vesicle called autophagosome, whose formation is coordinated by autophagy-related proteins (ATGs). Studies of yeast and Metazoa have identified approximately 40 ATGs. Genome projects for unicellular eukaryotes revealed that some ATGs are conserved in all eukaryotic supergroups but others have arisen or were lost during evolution in some specific lineages. In spite of an apparent reduction in the ATG molecular machinery found in parasitic protists, it has become clear that ATGs play an important role in stage differentiation or organelle maintenance, sometimes with an original function that is unrelated to canonical degradative autophagy. In this review, we aim to briefly summarize the current state of knowledge in parasitic protists, in the light of the latest important findings from more canonical model organisms. Determining the roles of ATGs and the diversity of their functions in various lineages is an important challenge for understanding the evolutionary background of autophagy.

scholarly journals Role of Host-Mediated Post-Translational Modifications (PTMs) in RNA Virus Pathogenesis

2020 ◽  
Vol 22 (1) ◽  
pp. 323
Author(s):  
Ramesh Kumar ◽  
Divya Mehta ◽  
Nimisha Mishra ◽  
Debasis Nayak ◽  
Sujatha Sunil
Keyword(s):  
Rna Virus ◽  
Viral Proteins ◽  
Post Translational Modification ◽  
Host Proteins ◽  
Viral Protein Synthesis ◽  
Post Translational Modifications ◽  
Small Proteins ◽  
Cellular Machinery ◽  
Chemical Groups

Being opportunistic intracellular pathogens, viruses are dependent on the host for their replication. They hijack host cellular machinery for their replication and survival by targeting crucial cellular physiological pathways, including transcription, translation, immune pathways, and apoptosis. Immediately after translation, the host and viral proteins undergo a process called post-translational modification (PTM). PTMs of proteins involves the attachment of small proteins, carbohydrates/lipids, or chemical groups to the proteins and are crucial for the proteins’ functioning. During viral infection, host proteins utilize PTMs to control the virus replication, using strategies like activating immune response pathways, inhibiting viral protein synthesis, and ultimately eliminating the virus from the host. PTM of viral proteins increases solubility, enhances antigenicity and virulence properties. However, RNA viruses are devoid of enzymes capable of introducing PTMs to their proteins. Hence, they utilize the host PTM machinery to promote their survival. Proteins from viruses belonging to the family: Togaviridae, Flaviviridae, Retroviridae, and Coronaviridae such as chikungunya, dengue, zika, HIV, and coronavirus are a few that are well-known to be modified. This review discusses various host and virus-mediated PTMs that play a role in the outcome during the infection.

scholarly journals SARS-CoV-2 Cellular Infection and Therapeutic Opportunities: Lessons Learned from Ebola Virus

Membranes ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 64
Author(s):  
Jordana Muñoz-Basagoiti ◽  
Daniel Perez-Zsolt ◽  
Jorge Carrillo ◽  
Julià Blanco ◽  
Bonaventura Clotet ◽  
...  
Keyword(s):  
Viral Entry ◽  
Ebola Virus ◽  
Lessons Learned ◽  
Productive Infection ◽  
Target Cells ◽  
Emerging Viruses ◽  
Highly Pathogenic ◽  
Life Threatening ◽  
Pathogenic Viruses ◽  
Cellular Machinery

Viruses rely on the cellular machinery to replicate and propagate within newly infected individuals. Thus, viral entry into the host cell sets up the stage for productive infection and disease progression. Different viruses exploit distinct cellular receptors for viral entry; however, numerous viral internalization mechanisms are shared by very diverse viral families. Such is the case of Ebola virus (EBOV), which belongs to the filoviridae family, and the recently emerged coronavirus SARS-CoV-2. These two highly pathogenic viruses can exploit very similar endocytic routes to productively infect target cells. This convergence has sped up the experimental assessment of clinical therapies against SARS-CoV-2 previously found to be effective for EBOV, and facilitated their expedited clinical testing. Here we review how the viral entry processes and subsequent replication and egress strategies of EBOV and SARS-CoV-2 can overlap, and how our previous knowledge on antivirals, antibodies, and vaccines against EBOV has boosted the search for effective countermeasures against the new coronavirus. As preparedness is key to contain forthcoming pandemics, lessons learned over the years by combating life-threatening viruses should help us to quickly deploy effective tools against novel emerging viruses.

scholarly journals Impact of DNA methylation on 3D genome structure

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Diana Buitrago ◽  
Mireia Labrador ◽  
Juan Pablo Arcon ◽  
Rafael Lema ◽  
Oscar Flores ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Chromatin Structure ◽  
Chromatin Condensation ◽  
Genome Structure ◽  
Dna Methyltransferases ◽  
Model System ◽  
Structure And Function ◽  
3D Genome ◽  
Cellular Machinery ◽  
And Function

AbstractDetermining the effect of DNA methylation on chromatin structure and function in higher organisms is challenging due to the extreme complexity of epigenetic regulation. We studied a simpler model system, budding yeast, that lacks DNA methylation machinery making it a perfect model system to study the intrinsic role of DNA methylation in chromatin structure and function. We expressed the murine DNA methyltransferases in Saccharomyces cerevisiae and analyzed the correlation between DNA methylation, nucleosome positioning, gene expression and 3D genome organization. Despite lacking the machinery for positioning and reading methylation marks, induced DNA methylation follows a conserved pattern with low methylation levels at the 5’ end of the gene increasing gradually toward the 3’ end, with concentration of methylated DNA in linkers and nucleosome free regions, and with actively expressed genes showing low and high levels of methylation at transcription start and terminating sites respectively, mimicking the patterns seen in mammals. We also see that DNA methylation increases chromatin condensation in peri-centromeric regions, decreases overall DNA flexibility, and favors the heterochromatin state. Taken together, these results demonstrate that methylation intrinsically modulates chromatin structure and function even in the absence of cellular machinery evolved to recognize and process the methylation signal.

scholarly journals Modulation of Cell–Cell Interactions in Drosophila Oocyte Development

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 274
Author(s):  
Matthew Antel ◽  
Mayu Inaba
Keyword(s):  
Cell Communication ◽  
Cell Interaction ◽  
Oocyte Development ◽  
Suitable Model ◽  
Physiological Regulation ◽  
Temporal Regulation ◽  
Cellular Processes ◽  
Cellular Machinery ◽  
Drosophila Ovary ◽  
Cell Cell

The Drosophila ovary offers a suitable model system to study the mechanisms that orchestrate diverse cellular processes. Oogenesis starts from asymmetric stem cell division, proper differentiation and the production of fully patterned oocytes equipped with all the maternal information required for embryogenesis. Spatial and temporal regulation of cell-cell interaction is particularly important to fulfill accurate biological outcomes at each step of oocyte development. Progress has been made in understanding diverse cell physiological regulation of signaling. Here we review the roles of specialized cellular machinery in cell-cell communication in different stages of oogenesis.

scholarly journals Epigenetic Defects ofGNASin Patients with Pseudohypoparathyroidism and Mild Features of Albright’s Hereditary Osteodystrophy

2007 ◽  
Vol 92 (6) ◽  
pp. 2370-2373 ◽  
Author(s):  
Guiomar Pérez de Nanclares ◽  
Eduardo Fernández-Rebollo ◽  
Izortze Santin ◽  
Beatriz García-Cuartero ◽  
Sonia Gaztambide ◽  
...  
Keyword(s):  
Albright’S Hereditary Osteodystrophy ◽  
Albright's Hereditary Osteodystrophy ◽  
Epigenetic Defects

scholarly journals Bovine Foamy Virus Transactivator BTas Interacts with Cellular RelB To Enhance Viral Transcription

2010 ◽  
Vol 84 (22) ◽  
pp. 11888-11897 ◽  
Author(s):  
Jian Wang ◽  
Juan Tan ◽  
Hongyan Guo ◽  
Qicheng Zhang ◽  
Rui Jia ◽  
...  
Keyword(s):  
Foamy Virus ◽  
Nuclear Factor Κb ◽  
Luciferase Reporter ◽  
Viral Transcription ◽  
Bovine Foamy Virus ◽  
Intracellular Parasites ◽  
Positive Feedback Circuit ◽  
Cellular Machinery

ABSTRACT Viruses are obligate intracellular parasites that depend on cellular machinery for their efficient transcription and replication. In a previous study we reported that bovine foamy virus (BFV) is able to activate the nuclear factor κB (NF-κB) pathway through the action of its transactivator BTas to enhance viral transcription. However, the mechanism used by NF-κB to enhance BFV transcription remains elusive. To address this question, we employed a yeast two-hybrid assay to screen for BTas-interacting proteins. We found that RelB, a member of NF-κB protein family, interacts with BTas. We confirmed the putative RelB-BTas interaction in vitro and in vivo and identified the protein regions responsible for the RelB-BTas interaction. Using a luciferase reporter assay, we next showed that RelB enhances BFV transcription (BTas-induced long terminal repeat [LTR] transactivation) and that this process requires both the localization of the RelB-BTas interaction in the nucleus and the Rel homology domain of RelB. The knockdown of the cellular endogenous RelB protein using small interfering RNA (siRNA) significantly attenuated BTas-induced LTR transcription. The results of chromatin immunoprecipitation (ChIP) analysis showed that endogenous RelB binds to the viral LTR in BFV-infected cells. Together, these results suggest that BFV engages the RelB protein as a cotransactivator of BTas to enhance viral transcription. In addition, our findings indicate that BFV infection upregulates cellular RelB expression through BTas-induced NF-κB activation. Thus, this study demonstrates the existence of a positive-feedback circuit in which BFV utilizes the host's NF-κB pathway through the RelB protein for efficient viral transcription.

scholarly journals Cyclophilin A as a target in the treatment of cytomegalovirus infections

2018 ◽  
Vol 26 ◽  
pp. 204020661881141 ◽  
Author(s):  
Ashwaq A Abdullah ◽  
Rasedee Abdullah ◽  
Zeenathul A Nazariah ◽  
Krishnan N Balakrishnan ◽  
Faez Firdaus J Abdullah ◽  
...  
Keyword(s):  
Viral Replication ◽  
Cyclosporin A ◽  
Cell Function ◽  
Antiviral Drug ◽  
Cyclophilin A ◽  
Dual Function ◽  
Host Cell Proteins ◽  
Early Protein ◽  
Cellular Machinery ◽  
Cytomegalovirus Infections

Background Viruses are obligate parasites that depend on the cellular machinery of the host to regenerate and manufacture their proteins. Most antiviral drugs on the market today target viral proteins. However, the more recent strategies involve targeting the host cell proteins or pathways that mediate viral replication. This new approach would be effective for most viruses while minimizing drug resistance and toxicity. Methods Cytomegalovirus replication, latency, and immune response are mediated by the intermediate early protein 2, the main protein that determines the effectiveness of drugs in cytomegalovirus inhibition. This review explains how intermediate early protein 2 can modify the action of cyclosporin A, an immunosuppressive, and antiviral drug. It also links all the pathways mediated by cyclosporin A, cytomegalovirus replication, and its encoded proteins. Results Intermediate early protein 2 can influence the cellular cyclophilin A pathway, affecting cyclosporin A as a mediator of viral replication or anti-cytomegalovirus drug. Conclusion Cyclosporin A has a dual function in cytomegalovirus pathogenesis. It has the immunosuppressive effect that establishes virus replication through the inhibition of T-cell function. It also has an anti-cytomegalovirus effect mediated by intermediate early protein 2. Both of these functions involve cyclophilin A pathway.

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