scholarly journals Linker histone H1.5 is an underestimated factor in differentiation and carcinogenesis

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Marthe Behrends ◽  
Olivia Engmann
Keyword(s):  
Cell Fate ◽  
Molecular Mechanisms ◽  
Control Cell ◽  
Mammalian Development ◽  
Research Attention ◽  
Post Translational Modifications ◽  
Linker Histones ◽  
The Family ◽  
Histone Modifying Enzymes ◽  
Fine Tune

Abstract Human histone H1.5, in mice called H1b, belongs to the family of linker histones (H1), which are key players in chromatin organization. These proteins sit on top of nucleosomes, in part to stabilize them, and recruit core histone modifying enzymes. Through subtype-specific deposition patterns and numerous post-translational modifications, they fine-tune gene expression and chromatin architecture, and help to control cell fate and homeostasis. However, even though it is increasingly implicated in mammalian development, H1.5 has not received as much research attention as its relatives. Recent studies have focused on its prognostic value in cancer patients and its contribution to tumorigenesis through specific molecular mechanisms. However, many functions of H1.5 are still poorly understood. In this review, we will summarize what is currently known about H1.5 and its function in cell differentiation and carcinogenesis. We will suggest key experiments that are required to understand the molecular network, in which H1.5 is embedded. These experiments will advance our understanding of the epigenetic reprogramming occurring in developmental and carcinogenic processes.

scholarly journals SOX2 for Stem Cell Therapy and Medical Use: Pros or Cons?

2020 ◽  
Vol 29 ◽  
pp. 096368972090756
Author(s):  
Hong-Meng Chuang ◽  
Mao-Hsuan Huang ◽  
Yu-Shuan Chen ◽  
Horng-Jyh Harn
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Fate ◽  
Cell Transplantation ◽  
Molecular Mechanisms ◽  
Control Cell ◽  
Critical Pathways ◽  
Stem Cell Isolation ◽  
And Storage

Stem cell transplantation is a fast-developing technique, which includes stem cell isolation, purification, and storage, and it is in high demand in the industry. In addition, advanced applications of stem cell transplantation, including differentiation, gene delivery, and reprogramming, are presently being studied in clinical trials. In contrast to somatic cells, stem cells are self-renewing and have the ability to differentiate; however, the molecular mechanisms remain unclear. SOX2 (sex-determining region Y [ SRY]-b ox 2) is one of the well-known reprogramming factors, and it has been recognized as an oncogene associated with cancer induction. The exclusion of SOX2 in reprogramming methodologies has been used as an alternative cancer treatment approach. However, the manner by which SOX2 induces oncogenic effects remains unclear, with most studies demonstrating its regulation of the cell cycle and no insight into the maintenance of cellular stemness. For controlling certain critical pathways, including Shh and Wnt pathways, SOX2 is considered irreplaceable and is required for the normal functioning of stem cells, particularly neural stem cells. In this report, we discussed the functions of SOX2 in both stem and cancer cells, as well as how this powerful regulator can be used to control cell fate.

scholarly journals Post-translational modifications regulate the activity of the growth restricting protease DA1

2021 ◽  
Author(s):  
Ying Chen ◽  
Dirk Inzé ◽  
Hannes Vanhaeren
Keyword(s):  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Organ Size ◽  
Negative Regulator ◽  
Renewable Energy Resources ◽  
Final Size ◽  
Post Translational Modifications ◽  
Important Trait ◽  
Multicellular Organisms ◽  
Fine Tune

Abstract Because plants are a primary food source and can form the basis for renewable energy resources, the final size of their organs is by far the most important trait to tackle when seeking increased plant productivity. Being multicellular organisms, plant organ size is mainly determined by the coordination between cell proliferation and cell expansion. The protease DA1 limits the duration of cell proliferation and hereby restricts final organ size. Since its initial identification as a negative regulator of organ growth, various transcriptional regulators of DA1, but also interacting proteins, have been identified. These interactors include cleavage substrates of DA1, but also proteins that modulate the activity of DA1 through post-translational modifications, such as ubiquitination, deubiquitination and phosphorylation. In addition, many players in the DA1 pathway display conserved phenotypes in other dicot and even monocot species. In this review, we give a timely overview of the complex, but intriguing molecular mechanisms that fine-tune the activity of DA1 and therefore final organ size, and we lay out a roadmap to identify and characterize substrates of proteases and frame the substrate cleavage events in their biological context.

scholarly journals Post-Translational Modifications in NETosis and NETs-Mediated Diseases

Biomolecules ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 369 ◽  
Author(s):  
Hamam ◽  
Palaniyar
Keyword(s):  
Histone Acetylation ◽  
Cancer Progression ◽  
Lupus Erythematosus ◽  
Molecular Mechanisms ◽  
Calcium Influx ◽  
Critical Role ◽  
Control Cell ◽  
Clear Understanding ◽  
Post Translational Modifications ◽  
Histone Citrullination

: Neutrophils undergo a unique form of cell death that generates neutrophil extracellular traps (NETs) that may help to neutralize invading pathogens and restore homeostasis. However, uncontrolled NET formation (NETosis) can result in numerous diseases that adversely affect health. Recent studies further elucidate the mechanistic details of the different forms of NETosis and their common end structure, as NETs were constantly found to contain DNA, modified histones and cytotoxic enzymes. In fact, emerging evidence reveal that the post translational modifications (PTMs) of histones in neutrophils have a critical role in regulating neutrophil death. Histone citrullination is shown to promote a rapid form of NET formation independent of NADPH oxidase (NOX), which relies on calcium influx. Interestingly, few studies suggest an association between histone citrullination and other types of PTMs to control cell survival and death, such as histone methylation. Even more exciting is the finding that histone acetylation has a biphasic effect upon NETosis, where histone deacetylase (HDAC) inhibitors promote baseline, NOX-dependent and -independent NETosis. However, increasing levels of histone acetylation suppresses NETosis, and to switch neutrophil death to apoptosis. Interestingly, in the presence of NETosis-promoting stimuli, high levels of HDACis limit both NETosis and apoptosis, and promote neutrophil survival. Recent studies also reveal the importance of the PTMs of neutrophils in influencing numerous pathologies. Histone modifications in NETs can act as a double-edged sword, as they are capable of altering multiple types of neutrophil death, and influencing numerous NET-mediated diseases, such as acute lung injury (ALI), thrombosis, sepsis, systemic lupus erythematosus, and cancer progression. A clear understanding of the role of different PTMs in neutrophils would be important for an understanding of the molecular mechanisms of NETosis, and to appropriately treat NETs-mediated diseases.

scholarly journals Developmental plasticity, cell fate specification and morphogenesis in the early mouse embryo

2014 ◽  
Vol 369 (1657) ◽  
pp. 20130538 ◽  
Author(s):  
Ivan Bedzhov ◽  
Sarah J. L. Graham ◽  
Chuen Yan Leung ◽  
Magdalena Zernicka-Goetz
Keyword(s):  
Cell Fate ◽  
Mouse Embryo ◽  
Developmental Plasticity ◽  
Molecular Mechanisms ◽  
Imaging Techniques ◽  
Cell Signalling ◽  
Three Dimensional ◽  
Early Embryo ◽  
Mammalian Development ◽  
Cell Fate Decisions

A critical point in mammalian development is when the early embryo implants into its mother's uterus. This event has historically been difficult to study due to the fact that it occurs within the maternal tissue and therefore is hidden from view. In this review, we discuss how the mouse embryo is prepared for implantation and the molecular mechanisms involved in directing and coordinating this crucial event. Prior to implantation, the cells of the embryo are specified as precursors of future embryonic and extra-embryonic lineages. These preimplantation cell fate decisions rely on a combination of factors including cell polarity, position and cell–cell signalling and are influenced by the heterogeneity between early embryo cells. At the point of implantation, signalling events between the embryo and mother, and between the embryonic and extraembryonic compartments of the embryo itself, orchestrate a total reorganization of the embryo, coupled with a burst of cell proliferation. New developments in embryo culture and imaging techniques have recently revealed the growth and morphogenesis of the embryo at the time of implantation, leading to a new model for the blastocyst to egg cylinder transition. In this model, pluripotent cells that will give rise to the fetus self-organize into a polarized three-dimensional rosette-like structure that initiates egg cylinder formation.

scholarly journals Coordinating cell polarity and cell cycle progression: what can we learn from flies and worms?

Open Biology ◽  
2013 ◽  
Vol 3 (8) ◽  
pp. 130083 ◽  
Author(s):  
Anna Noatynska ◽  
Nicolas Tavernier ◽  
Monica Gotta ◽  
Lionel Pintard
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Cell Fate ◽  
Cell Polarity ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Asymmetric Cell Division ◽  
Control Cell ◽  
Model Organisms ◽  
Cycle Progression

Spatio-temporal coordination of events during cell division is crucial for animal development. In recent years, emerging data have strengthened the notion that tight coupling of cell cycle progression and cell polarity in dividing cells is crucial for asymmetric cell division and ultimately for metazoan development. Although it is acknowledged that such coupling exists, the molecular mechanisms linking the cell cycle and cell polarity machineries are still under investigation. Key cell cycle regulators control cell polarity, and thus influence cell fate determination and/or differentiation, whereas some factors involved in cell polarity regulate cell cycle timing and proliferation potential. The scope of this review is to discuss the data linking cell polarity and cell cycle progression, and the importance of such coupling for asymmetric cell division. Because studies in model organisms such as Caenorhabditis elegans and Drosophila melanogaster have started to reveal the molecular mechanisms of this coordination, we will concentrate on these two systems. We review examples of molecular mechanisms suggesting a coupling between cell polarity and cell cycle progression.

FoxO transcription factors in oxidative stress response and ageing – a new fork on the way to longevity?

2008 ◽  
Vol 389 (3) ◽  
pp. 279-283 ◽  
Author(s):  
Daniel G. Sedding
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Cellular Functions ◽  
Post Translational Modifications ◽  
Cellular Effects ◽  
Forkhead Box ◽  
Foxo Transcription Factors

Abstract Forkhead box O (FoxO) transcription factors are important downstream targets of the PI3K/Akt signaling pathway and crucial regulators of cell fate. This function of FoxOs relies on their ability to control diverse cellular functions, including proliferation, differentiation, apoptosis, DNA repair, defense against oxidative stress and ageing. FoxOs are regulated by a variety of different growth factors and hormones, and their activity is tightly controlled by post-translational modifications, including phosphorylation, acetylation, ubiquitination and interaction with different proteins and transcription factors. This brief review focuses on the molecular mechanisms, cellular effects and resulting organismal phenotypes generated by differentially regulated FoxO proteins and discusses our current understanding of the role of FoxOs in disease and ageing processes.

Epigenetic markers and their cross-talk

2010 ◽  
Vol 48 ◽  
pp. 45-61 ◽  
Author(s):  
Stefan Winter ◽  
Wolfgang Fischle
Keyword(s):  
Cell Fate ◽  
Cross Talk ◽  
Cell Cycle Progression ◽  
Specific Binding ◽  
Cell Fate Determination ◽  
Chromatin Modifications ◽  
Cycle Progression ◽  
Post Translational Modifications ◽  
Histone Modifying Enzymes ◽  
Temporal And Spatial

Post-translational modifications of histone proteins in conjunction with DNA methylation represent important events in the regulation of local and global genome functions. Advances in the study of these chromatin modifications established temporal and spatial co-localization of several distinct ‘marks’ on the same histone and/or the same nucleosome. Such complex modification patterns suggest the possibility of combinatorial effects. This idea was originally proposed to establish a code of histone modifications that regulates the interpretation of the genetic code of DNA. Indeed, interdependency of different modifications is now well documented in the literature. Our current understanding is that the function of a given histone modification is influenced by neighbouring or additional modifications. Such context sensitivity of the readout of a modification provides more flexible translation than would be possible if distinct modifications function as isolated units. The mechanistic principles for modification cross-talk can originate in the modulation of the activity of histone-modifying enzymes or may be due to selective recognition of these marks via modification of specific binding proteins. In the present chapter, we discuss fundamental biochemical principles of modification cross-talk and reflect on the interplay of chromatin marks in cellular signalling, cell-cycle progression and cell-fate determination.

scholarly journals Molecular Pathways Involved in the Development of Congenital Erythrocytosis

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1150
Author(s):  
Jana Tomc ◽  
Nataša Debeljak
Keyword(s):  
Signal Transduction ◽  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Oxygen Affinity ◽  
Molecular Pathways ◽  
Disease Development ◽  
Post Translational Modifications ◽  
Hemoglobin Oxygen Affinity ◽  
Insight Into ◽  
Idiopathic Erythrocytosis

Patients with idiopathic erythrocytosis are directed to targeted genetic testing including nine genes involved in oxygen sensing pathway in kidneys, erythropoietin signal transduction in pre-erythrocytes and hemoglobin-oxygen affinity regulation in mature erythrocytes. However, in more than 60% of cases the genetic cause remains undiagnosed, suggesting that other genes and mechanisms must be involved in the disease development. This review aims to explore additional molecular mechanisms in recognized erythrocytosis pathways and propose new pathways associated with this rare hematological disorder. For this purpose, a comprehensive review of the literature was performed and different in silico tools were used. We identified genes involved in several mechanisms and molecular pathways, including mRNA transcriptional regulation, post-translational modifications, membrane transport, regulation of signal transduction, glucose metabolism and iron homeostasis, which have the potential to influence the main erythrocytosis-associated pathways. We provide valuable theoretical information for deeper insight into possible mechanisms of disease development. This information can be also helpful to improve the current diagnostic solutions for patients with idiopathic erythrocytosis.

scholarly journals Targeting AURKA in Cancer: molecular mechanisms and opportunities for Cancer therapy

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Ruijuan Du ◽  
Chuntian Huang ◽  
Kangdong Liu ◽  
Xiang Li ◽  
Zigang Dong
Keyword(s):  
Cancer Therapy ◽  
Molecular Mechanisms ◽  
Aurora Kinase ◽  
Interacting Proteins ◽  
Multiple Tumor ◽  
Oncogenic Pathways ◽  
Wide Range ◽  
The Family ◽  
Tumor Types ◽  
Cancer Tissues

AbstractAurora kinase A (AURKA) belongs to the family of serine/threonine kinases, whose activation is necessary for cell division processes via regulation of mitosis. AURKA shows significantly higher expression in cancer tissues than in normal control tissues for multiple tumor types according to the TCGA database. Activation of AURKA has been demonstrated to play an important role in a wide range of cancers, and numerous AURKA substrates have been identified. AURKA-mediated phosphorylation can regulate the functions of AURKA substrates, some of which are mitosis regulators, tumor suppressors or oncogenes. In addition, enrichment of AURKA-interacting proteins with KEGG pathway and GO analysis have demonstrated that these proteins are involved in classic oncogenic pathways. All of this evidence favors the idea of AURKA as a target for cancer therapy, and some small molecules targeting AURKA have been discovered. These AURKA inhibitors (AKIs) have been tested in preclinical studies, and some of them have been subjected to clinical trials as monotherapies or in combination with classic chemotherapy or other targeted therapies.

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