scholarly journals Elongator: An Ancestral Complex Driving Transcription and Migration through Protein Acetylation

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Catherine Creppe ◽  
Marcus Buschbeck
Keyword(s):  
Intracellular Trafficking ◽  
Histone H3 ◽  
Transferase Activity ◽  
Transcriptional Elongation ◽  
Protein Acetylation ◽  
Cellular Functions ◽  
Elongator Complex ◽  
And Migration ◽  
Inducible Genes ◽  
Distal Gene

Elongator is an evolutionary highly conserved complex. At least two of its cellular functions rely on the intrinsic lysine acetyl-transferase activity of the Elongator complex. Its two known substrates—Histone H3 and α-Tubulin—reflect the different roles of Elongator in the cytosol and the nucleus. A picture seems to emerge in which nuclear Elongator could regulate the transcriptional elongation of a subset of stress-inducible genes through acetylation of Histone H3 in the promoter-distal gene body. In the cytosol, Elongator-mediated acetylation of α-Tubulin contributes to intracellular trafficking and cell migration. Defects in both functions of Elongator have been implicated in neurodegenerative disorders.

scholarly journals Promoter-specific changes in initiation, elongation and homeostasis of histone H3 acetylation during CBP/p300 inhibition

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Emily Hsu ◽  
Nathan R Zemke ◽  
Arnold J Berk
Keyword(s):  
Rna Polymerase Ii ◽  
Control Point ◽  
Histone H3 ◽  
Airway Epithelial Cells ◽  
Proximal Region ◽  
Transferase Activity ◽  
Transcriptional Elongation ◽  
Elongation Complex ◽  
Histone H3 Acetylation ◽  
H3 Acetylation

Regulation of RNA Polymerase II (Pol2) elongation in the promoter proximal region is an important and ubiquitous control point for gene expression in metazoans. We report that transcription of the adenovirus 5 E4 region is regulated during the release of paused Pol2 into productive elongation by recruitment of the super elongation complex (SEC), dependent on promoter H3K18/27 acetylation by CBP/p300. We also establish that this is a general transcriptional regulatory mechanism that applies to ~6% of expressed protein-coding genes in primary human airway epithelial cells. We observed that a homeostatic mechanism maintains promoter, but not enhancer H3K18/27ac in response to extensive inhibition of CBP/p300 acetyl transferase activity by the highly specific small molecule inhibitor A-485. Further, our results suggest a function for BRD4 association at enhancers in regulating paused Pol2 release at nearby promoters. Taken together, our results uncover processes regulating transcriptional elongation by promoter region histone H3 acetylation and homeostatic maintenance of promoter, but not enhancer, H3K18/27ac in response to inhibition of CBP/p300 acetyl transferase activity.

scholarly journals Promoter-specific changes in initiation, elongation and homeostasis of histone H3 acetylation during CBP/p300 Inhibition

2020 ◽  
Author(s):  
E Hsu ◽  
NR Zemke ◽  
AJ Berk
Keyword(s):  
Rna Polymerase Ii ◽  
Control Point ◽  
Histone H3 ◽  
Airway Epithelial Cells ◽  
Proximal Region ◽  
Transferase Activity ◽  
Transcriptional Elongation ◽  
Elongation Complex ◽  
Histone H3 Acetylation ◽  
H3 Acetylation

SummaryRegulation of RNA Polymerase II (Pol2) elongation in the promoter proximal region is an important and ubiquitous control point for gene expression in metazoan cells. We report that transcription of the adenovirus 5 E4 region is regulated during the release of paused Pol2 into productive elongation by recruitment of the super elongation complex (SEC), dependent on promoter H3K18/27 acetylation by CBP/p300. We also establish that this is a general transcriptional regulatory mechanism for ∼6% of genes expressed with FPKM>1 in primary human airway epithelial cells. We observed that a homeostatic mechanism maintains promoter, but not enhancer H3K18/27ac in response to extensive inhibition of CBP/p300 acetyl transferase activity by the highly specific small molecule inhibitor A-485. Further, our results suggest a function for BRD4 association at enhancers in regulating paused Pol2 release at nearby promoters. Taken together, our results uncover processes regulating transcriptional elongation by promoter region histone H3 acetylation and homeostatic maintenance of promoter, but not enhancer, H3K18/27ac in response to inhibition of CBP/p300 acetyl transferase activity.

scholarly journals Ash1l Methylates Lys36 of Histone H3 Independently of Transcriptional Elongation to Counteract Polycomb Silencing

PLoS Genetics ◽  
2013 ◽  
Vol 9 (11) ◽  
pp. e1003897 ◽  
Author(s):  
Hitomi Miyazaki ◽  
Ken Higashimoto ◽  
Yukari Yada ◽  
Takaho A. Endo ◽  
Jafar Sharif ◽  
...  
Keyword(s):  
Histone H3 ◽  
Transcriptional Elongation

scholarly journals Nonneuronal Cholinergic System in Breast Tumors and Dendritic Cells: Does It Improve or Worsen the Response to Tumor?

2013 ◽  
Vol 2013 ◽  
pp. 1-12
Author(s):  
Marisa Vulcano ◽  
María Gabriela Lombardi ◽  
María Elena Sales
Keyword(s):  
Dendritic Cells ◽  
Cholinergic System ◽  
Parasympathetic Nervous System ◽  
Immune Cell ◽  
Breast Tumors ◽  
Cell Types ◽  
Cellular Functions ◽  
And Migration ◽  
And Function

Besides being the main neurotransmitter in the parasympathetic nervous system, acetylcholine (ACh) can act as a signaling molecule in nonneuronal tissues. For this reason, ACh and the enzymes that synthesize and degrade it (choline acetyltransferase and acetylcholinesterase) as well as muscarinic (mAChRs) and nicotinic receptors conform the non-neuronal cholinergic system (nNCS). It has been reported that nNCS regulates basal cellular functions including survival, proliferation, adhesion, and migration. Moreover, nNCS is broadly expressed in tumors and in different components of the immune system. In this review, we summarize the role of nNCS in tumors and in different immune cell types focusing on the expression and function of mAChRs in breast tumors and dendritic cells (DCs) and discussing the role of DCs in breast cancer.

scholarly journals Preconditioning by Hydrogen Peroxide Enhances Multiple Properties of HumanDecidua BasalisMesenchymal Stem/Multipotent Stromal Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
T. Khatlani ◽  
D. Algudiri ◽  
R. Alenzi ◽  
A. M. Al Subayyil ◽  
F. M. Abomaray ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Stem Cell ◽  
Cellular Functions ◽  
Beneficial Effects ◽  
Decidua Basalis ◽  
Expression Of Genes ◽  
Toxic Environment ◽  
Stress Environment ◽  
And Migration ◽  
Hostile Environments

Stem cell-based therapies rely on stem cell ability to repair in an oxidative stress environment. Preconditioning of mesenchymal stem cells (MSCs) to a stress environment has beneficial effects on their ability to repair injured tissues. We previously reported that MSCs from thedecidua basalis(DBMSCs) of human placenta have many important cellular functions that make them potentially useful for cell-based therapies. Here, we studied the effect of DBMSC preconditioning to a stress environment. DBMSCs were exposed to various concentrations of hydrogen peroxide (H2O2), and their functions were then assessed. DBMSC expression of immune molecules after preconditioning was also determined. DBMSC preconditioning with H2O2enhanced their proliferation, colonogenicity, adhesion, and migration. In addition, DBMSCs regardless of H2O2treatment displayed antiangiogenic activity. H2O2preconditioning also increased DBMSC expression of genes that promote cellular functions and decreased the expression of genes, which have opposite effect on their functions. Preconditioning also reduced DBMSC expression of IL-1β, but had no effects on the expression of other immune molecules that promote proliferation, adhesion, and migration. These data show that DBMSCs resist a toxic environment, which adds to their potential as a candidate stem cell type for treating various diseases in hostile environments.

scholarly journals Relating GPI-Anchored Ly6 Proteins uPAR and CD59 to Viral Infection

Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1060 ◽  
Author(s):  
Yu ◽  
Murthy ◽  
Liu
Keyword(s):  
Viral Infection ◽  
Viral Entry ◽  
Current Knowledge ◽  
Cellular Functions ◽  
Lymphocyte Antigen ◽  
Host Interaction ◽  
Type Plasminogen Activator ◽  
Cell Adhesion And Migration ◽  
And Migration

The Ly6 (lymphocyte antigen-6)/uPAR (urokinase-type plasminogen activator receptor) superfamily protein is a group of molecules that share limited sequence homology but conserved three-fingered structures. Despite diverse cellular functions, such as in regulating host immunity, cell adhesion, and migration, the physiological roles of these factors in vivo remain poorly characterized. Notably, increasing research has focused on the interplays between Ly6/uPAR proteins and viral pathogens, the results of which have provided new insight into viral entry and virus–host interactions. While LY6E (lymphocyte antigen 6 family member E), one key member of the Ly6E/uPAR-family proteins, has been extensively studied, other members have not been well characterized. Here, we summarize current knowledge of Ly6/uPAR proteins related to viral infection, with a focus on uPAR and CD59. Our goal is to provide an up-to-date view of the Ly6/uPAR-family proteins and associated virus–host interaction and viral pathogenesis.

scholarly journals Polycystins in Colorectal Cancer

2018 ◽  
Vol 20 (1) ◽  
pp. 104 ◽  
Author(s):  
Antonios Gargalionis ◽  
Efthimia Basdra ◽  
Athanasios Papavassiliou
Keyword(s):  
Colorectal Cancer ◽  
Calcium Influx ◽  
Cellular Functions ◽  
Selective Treatment ◽  
Adhesion Protein ◽  
Protein Molecules ◽  
Transduction Mechanisms ◽  
Novel Biomarkers ◽  
And Migration ◽  
Focal Adhesion Protein

Cell and extracellular matrix (ECM) biomechanics emerge as a distinct feature during the development and progression of colorectal cancer (CRC). Polycystins are core mechanosensitive protein molecules that mediate mechanotransduction in a variety of epithelial cells. Polycystin-1 (PC1) and polycystin-2 (PC2) are engaged in signal transduction mechanisms and during alterations in calcium influx, which regulate cellular functions such as proliferation, differentiation, orientation, and migration in cancer cells. Recent findings implicate polycystins in the deregulation of such functions and the formation of CRC invasive phenotypes. Polycystins participate in all aspects of the cell’s biomechanical network, from the perception of extracellular mechanical cues to focal adhesion protein and nuclear transcriptional complexes. Therefore, polycystins could be employed as novel biomarkers and putative targets of selective treatment in CRC.

scholarly journals Primary Cilia and Calcium Signaling Interactions

2020 ◽  
Vol 21 (19) ◽  
pp. 7109
Author(s):  
Hannah Saternos ◽  
Sidney Ley ◽  
Wissam AbouAlaiwi
Keyword(s):  
Primary Cilia ◽  
Cell Types ◽  
Cellular Level ◽  
Cellular Functions ◽  
Complex Processes ◽  
Secondary Messenger ◽  
Body Patterning ◽  
Motile Cilia ◽  
And Migration ◽  
Context Specific

The calcium ion (Ca2+) is a diverse secondary messenger with a near-ubiquitous role in a vast array of cellular processes. Cilia are present on nearly every cell type in either a motile or non-motile form; motile cilia generate fluid flow needed for a variety of biological processes, such as left–right body patterning during development, while non-motile cilia serve as the signaling powerhouses of the cell, with vital singling receptors localized to their ciliary membranes. Much of the research currently available on Ca2+-dependent cellular actions and primary cilia are tissue-specific processes. However, basic stimuli-sensing pathways, such as mechanosensation, chemosensation, and electrical sensation (electrosensation), are complex processes entangled in many intersecting pathways; an overview of proposed functions involving cilia and Ca2+ interplay will be briefly summarized here. Next, we will focus on summarizing the evidence for their interactions in basic cellular activities, including the cell cycle, cell polarity and migration, neuronal pattering, glucose-mediated insulin secretion, biliary regulation, and bone formation. Literature investigating the role of cilia and Ca2+-dependent processes at a single-cellular level appears to be scarce, though overlapping signaling pathways imply that cilia and Ca2+ interact with each other on this level in widespread and varied ways on a perpetual basis. Vastly different cellular functions across many different cell types depend on context-specific Ca2+ and cilia interactions to trigger the correct physiological responses, and abnormalities in these interactions, whether at the tissue or the single-cell level, can result in diseases known as ciliopathies; due to their clinical relevance, pathological alterations of cilia function and Ca2+ signaling will also be briefly touched upon throughout this review.

scholarly journals New Insights into ADAMTS Metalloproteases in the Central Nervous System

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 403 ◽  
Author(s):  
Yamina Mohamedi ◽  
Tania Fontanil ◽  
Teresa Cobo ◽  
Santiago Cal ◽  
Alvaro J. Obaya
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Plasticity ◽  
Axonal Guidance ◽  
Cellular Functions ◽  
Tissue Organization ◽  
The Central Nervous System ◽  
A Disintegrin And Metalloproteinase ◽  
And Migration ◽  
Neuronal Disorders

Components of the extracellular matrix (ECM) are key players in regulating cellular functions throughout the whole organism. In fact, ECM components not only participate in tissue organization but also contribute to processes such as cellular maintenance, proliferation, and migration, as well as to support for various signaling pathways. In the central nervous system (CNS), proteoglycans of the lectican family, such as versican, aggrecan, brevican, and neurocan, are important constituents of the ECM. In recent years, members of this family have been found to be involved in the maintenance of CNS homeostasis and to participate directly in processes such as the organization of perineural nets, the regulation of brain plasticity, CNS development, brain injury repair, axonal guidance, and even the altering of synaptic responses. ADAMTSs are a family of “A disintegrin and metalloproteinase with thrombospondin motifs” proteins that have been found to be involved in a multitude of processes through the degradation of lecticans and other proteoglycans. Recently, alterations in ADAMTS expression and activity have been found to be involved in neuronal disorders such as stroke, neurodegeneration, schizophrenia, and even Alzheimer’s disease, which in turn may suggest their potential use as therapeutic targets. Herein, we summarize the different roles of ADAMTSs in regulating CNS events through interactions and the degradation of ECM components (more specifically, the lectican family of proteoglycans).

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