scholarly journals Telomeres and Cancer: Resolving the Paradox

2021 ◽  
Vol 5 (1) ◽  
pp. 59-77
Author(s):  
Joe Nassour ◽  
Tobias T. Schmidt ◽  
Jan Karlseder
Keyword(s):  
Cell Cycle ◽  
Current Knowledge ◽  
Cancer Etiology ◽  
Dna Damage Signaling ◽  
Cellular Events ◽  
Genomic Aberrations ◽  
New Perspective ◽  
Tumor Suppressive Function ◽  
Linear Chromosomes

Decades of study on cell cycle regulation have provided great insight into human cellular life span barriers, as well as their dysregulation during tumorigenesis. Telomeres, the extremities of linear chromosomes, perform an essential role in implementing these proliferative boundaries and preventing the propagation of potentially cancerous cells. The tumor-suppressive function of telomeres relies on their ability to initiate DNA damage signaling pathways and downstream cellular events, ranging from cell cycle perturbation to inflammation and cell death. While the tumor-suppressor role of telomeres is undoubtable, recent advances have pointed to telomeres as a major source of many of the genomic aberrations found in both early- and late-stage cancers, including the most recently discovered mutational phenomenon of chromothripsis. Telomere shortening appears as a double-edged sword that can function in opposing directions in carcinogenesis. This review focuses on the current knowledge of the dual role of telomeres in cancer and suggests a new perspective to reconcile the paradox of telomeres and their implications in cancer etiology.

scholarly journals Role of CDK1 in Translational Regulation in the M-Phase

2020 ◽  
Author(s):  
Jaroslav Kalous ◽  
Denisa Jansova ◽  
Andrej Susor
Keyword(s):  
Cell Cycle ◽  
Protein Synthesis ◽  
Translational Regulation ◽  
Gene Expression Regulation ◽  
Translational Initiation ◽  
Initiation Factors ◽  
Cellular Events ◽  
M Phase ◽  
Mitosis And Meiosis

Cyclin dependent kinase 1 (CDK1) has been primarily identified as a key cell cycle regulator in both mitosis and meiosis. Recently, an extramitotic function of CDK1 emerged when evidence was found that CDK1 is involved in many cellular events that are essential for cell proliferation and survival. In this review we summarize the involvement of active CDK1 in the initiation and elongation steps of protein synthesis in eukaryotes. During its activation CDK1 influences the initiation of protein synthesis, promotes the activity of specific translational initiation factors and affects the functioning of a subset of elongation factors. Our review provides insights into gene expression regulation during the transcriptionally silent cell cycle/M-phase and describes quantitative and qualitative translational changes based on the extramitotic role of the cell cycle master regulator CDK1, to optimize temporal synthesis of proteins to sustain division-related processes: mitosis and cytokinesis.

scholarly journals Wound Healing and Omega-6 Fatty Acids: From Inflammation to Repair

2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Jéssica R. Silva ◽  
Beatriz Burger ◽  
Carolina M. C. Kühl ◽  
Thamiris Candreva ◽  
Mariah B. P. dos Anjos ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Wound Healing ◽  
Current Knowledge ◽  
Phagocytic Capacity ◽  
Cellular Events ◽  
Species Survival ◽  
Evolutionarily Conserved ◽  
Omega 6 ◽  
Cell Migration And Proliferation

Wound healing is an evolutionarily conserved process that is essential for species survival. Wound healing involves a series of biochemical and cellular events that are tightly controlled, divided into 3 concomitant and overlapping phases: inflammation, proliferation, and remodelling. Poor wound healing or a chronic wound represents a silent epidemic that affects billions of people worldwide. Considering the involvement of immune cells in its resolution, recent studies are focused on investigating the roles of immune nutrients such as amino acids, minerals, and fatty acids on wound healing. Among the fatty acids, much attention has been given to omega-6 (ω-6) fatty acids since they can modulate cell migration and proliferation, phagocytic capacity, and production of inflammatory mediators. The present review summarizes current knowledge about the role of ω-6 fatty acids in the wound healing context.

scholarly journals The Multiple Roles of the Cdc14 Phosphatase in Cell Cycle Control

2020 ◽  
Vol 21 (3) ◽  
pp. 709
Author(s):  
Javier Manzano-López ◽  
Fernando Monje-Casas
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Current Knowledge ◽  
Cell Cycle Control ◽  
Multiple Roles ◽  
Special Focus ◽  
Cyclin Dependent Kinase ◽  
Yeast Saccharomyces Cerevisiae ◽  
Cycle Progression

The Cdc14 phosphatase is a key regulator of mitosis in the budding yeast Saccharomyces cerevisiae. Cdc14 was initially described as playing an essential role in the control of cell cycle progression by promoting mitotic exit on the basis of its capacity to counteract the activity of the cyclin-dependent kinase Cdc28/Cdk1. A compiling body of evidence, however, has later demonstrated that this phosphatase plays other multiple roles in the regulation of mitosis at different cell cycle stages. Here, we summarize our current knowledge about the pivotal role of Cdc14 in cell cycle control, with a special focus in the most recently uncovered functions of the phosphatase.

scholarly journals The dynamics of the nuclear environment and their impact on gene function

2020 ◽  
Author(s):  
Lorena Zannino ◽  
Claudio Casali ◽  
Stella Siciliani ◽  
Marco Biggiogera
Keyword(s):  
Cell Cycle ◽  
Gene Function ◽  
Spatial Organization ◽  
Current Knowledge ◽  
Cellular Phenotype ◽  
High Concentration ◽  
Gene Functions ◽  
Nuclear Environment ◽  
Over Time

Abstract In the last decades, it has become increasingly clear how the modulation of spatial organization of chromatin over time and through the cell cycle is closely connected to gene function regulation. Different physicochemical stimuli contribute to the realization of specific transcriptional programs and finally to a specific cellular phenotype. In this review, we aim to describe the current knowledge about the dynamics regulating the movements and the interactions of molecules within the nucleus and their impact on gene functions. In particular, taking into account that these forces exert their effect in a nuclear environment characterized by a high concentration of molecules, we will discuss the role of proteins and structures that regulate these movements and transduce physicochemical signals acting on the cell to the nucleus.

scholarly journals The polyploid state plays a tumor suppressive role in the liver

2017 ◽  
Author(s):  
Shuyuan Zhang ◽  
Keijin Zhou ◽  
Xin Luo ◽  
Lin Li ◽  
Liem Nguyen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Liver Injury ◽  
Liver Function ◽  
Functional Role ◽  
High Fat ◽  
Cell Cycle Genes ◽  
Oncogene Activation ◽  
Genomic Aberrations

AbstractMost cells in the liver are polyploid, but the functional role of polyploidy is unknown. Polyploidization normally occurs through cytokinesis failure and endoreduplication around the time of weaning. To interrogate the function of polyploidy while avoiding irreversible manipulations of essential cell cycle genes, we developed multiple orthogonal mouse models to transiently and potently alter liver ploidy. Premature weaning, as well as in vivo knockdown of E2f8 or Anln, allowed us to toggle between diploid and polyploid states. While there was no impact of ploidy alterations on liver function, metabolism, or regeneration, hyperpolyploid mice suppressed and hyperdiploid mice accelerated tumorigenesis in mutagen and high fat induced models. Mechanistically, the diploid state was more susceptible to Cas9-mediated tumor suppressor loss but was similarly susceptible to MYC oncogene activation, indicating that ploidy differentially protected the liver from distinct genomic aberrations. Our work suggests that polyploidy evolved to prevent malignant outcomes of liver injury.

scholarly journals Role of Cyclin-Dependent Kinase 1 in Translational Regulation in the M-Phase

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1568
Author(s):  
Jaroslav Kalous ◽  
Denisa Jansová ◽  
Andrej Šušor
Keyword(s):  
Cell Cycle ◽  
Protein Synthesis ◽  
Translational Regulation ◽  
Gene Expression Regulation ◽  
Cyclin Dependent Kinase ◽  
Translational Initiation ◽  
Initiation Factors ◽  
Cellular Events ◽  
M Phase

Cyclin dependent kinase 1 (CDK1) has been primarily identified as a key cell cycle regulator in both mitosis and meiosis. Recently, an extramitotic function of CDK1 emerged when evidence was found that CDK1 is involved in many cellular events that are essential for cell proliferation and survival. In this review we summarize the involvement of CDK1 in the initiation and elongation steps of protein synthesis in the cell. During its activation, CDK1 influences the initiation of protein synthesis, promotes the activity of specific translational initiation factors and affects the functioning of a subset of elongation factors. Our review provides insights into gene expression regulation during the transcriptionally silent M-phase and describes quantitative and qualitative translational changes based on the extramitotic role of the cell cycle master regulator CDK1 to optimize temporal synthesis of proteins to sustain the division-related processes: mitosis and cytokinesis.

scholarly journals TSH and Thyrotropic Agonists: Key Actors in Thyroid Homeostasis

2012 ◽  
Vol 2012 ◽  
pp. 1-29 ◽  
Author(s):  
Johannes W. Dietrich ◽  
Gabi Landgrafe ◽  
Elisavet H. Fotiadou
Keyword(s):  
Dynamic Behaviour ◽  
Reference Range ◽  
Current Knowledge ◽  
Epidemiological Investigation ◽  
Mathematical Methods ◽  
Systems Perspective ◽  
The Past ◽  
New Perspective ◽  
Critical Components

This paper provides the reader with an overview of our current knowledge of hypothalamic-pituitary-thyroid feedback from a cybernetic standpoint. Over the past decades we have gained a plethora of information from biochemical, clinical, and epidemiological investigation, especially on the role of TSH and other thyrotropic agonists as critical components of this complex relationship. Integrating these data into a systems perspective delivers new insights into static and dynamic behaviour of thyroid homeostasis. Explicit usage of this information with mathematical methods promises to deliver a better understanding of thyrotropic feedback control and new options for personalised diagnosis of thyroid dysfunction and targeted therapy, also by permitting a new perspective on the conundrum of the TSH reference range.

scholarly journals Histone supply: Multitiered regulation ensures chromatin dynamics throughout the cell cycle

2018 ◽  
Vol 218 (1) ◽  
pp. 39-54 ◽  
Author(s):  
Shweta Mendiratta ◽  
Alberto Gatto ◽  
Genevieve Almouzni
Keyword(s):  
Cell Cycle ◽  
Current Knowledge ◽  
Building Blocks ◽  
Histone Variants ◽  
Cell Fates ◽  
Chromatin Dynamics ◽  
Posttranscriptional Processing ◽  
Cellular Dysfunction ◽  
Different Levels

As the building blocks of chromatin, histones are central to establish and maintain particular chromatin states associated with given cell fates. Importantly, histones exist as distinct variants whose expression and incorporation into chromatin are tightly regulated during the cell cycle. During S phase, specialized replicative histone variants ensure the bulk of the chromatinization of the duplicating genome. Other non-replicative histone variants deposited throughout the cell cycle at specific loci use pathways uncoupled from DNA synthesis. Here, we review the particular dynamics of expression, cellular transit, assembly, and disassembly of replicative and non-replicative forms of the histone H3. Beyond the role of histone variants in chromatin dynamics, we review our current knowledge concerning their distinct regulation to control their expression at different levels including transcription, posttranscriptional processing, and protein stability. In light of this unique regulation, we highlight situations where perturbations in histone balance may lead to cellular dysfunction and pathologies.

scholarly journals A comprehensive transcriptomic view on the role of SMAD4 gene by RNAi-mediated knockdown in porcine follicular granulosa cells

Reproduction ◽  
2016 ◽  
Vol 152 (1) ◽  
pp. 81-89 ◽  
Author(s):  
Lifan Zhang ◽  
Xing Du ◽  
Shengjuan Wei ◽  
Dongfeng Li ◽  
Qifa Li
Keyword(s):  
Cell Cycle ◽  
Signaling Pathway ◽  
Granulosa Cells ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Current Knowledge ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment

As a key mediator of the transforming growth factor-beta (TGF-β) signaling pathway, which plays a pivotal role in regulating mammalian reproductive performance, Sma- and Mad-related protein 4 (SMAD4) is closely associated with the development of ovarian follicular. However, current knowledge of the genome-wide view on the role ofSMAD4gene in mammalian follicular granulosa cells (GCs) is still largely unknown. In the present study, RNA-Seq was performed to investigate the effects ofSMAD4knockdown by RNA interference (SMAD4-siRNA) in porcine follicular GCs. A total of 1025 differentially expressed genes (DEGs), including 530 upregulated genes and 495 downregulated genes, were identified inSMAD4-siRNA treated GCs compared with that treated with NC-siRNA. Furthermore, functional enrichment analysis indicated that upregulated DEGs inSMAD4-siRNA treated cells were mainly enriched in cell-cycle related processes, interferon signaling pathway, and immune system process, while downregulated DEGs inSMAD4-siRNA treated cells were mainly involved in extracellular matrix organization/disassembly, pathogenesis, and cell adhesion. In particular, cell cycle and TGF-β signaling pathway were discovered as the canonical pathways changed underSMAD4-silencing. Taken together, our data revealsSMAD4knockdown alters the expression of numerous genes involved in key biological processes of the development of follicular GCs and provides a novel global clue of the role ofSMAD4gene in porcine follicular GCs, thus improving our understanding of regulatory mechanisms ofSMAD4gene in follicular development.

scholarly journals Fostering Inflammatory Bowel Disease: Sphingolipid Strategies to Join Forces

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Loubna Abdel Hadi ◽  
Clara Di Vito ◽  
Laura Riboni
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Intestinal Cell ◽  
Cellular Events ◽  
Body Of Knowledge ◽  
Inflammatory Bowel ◽  
Complex Sphingolipids

Complex sphingolipids are essential structural components of intestinal membranes, providing protection and integrity to the intestinal mucosa and regulating intestinal absorption processes. The role of sphingolipid signaling has been established in numerous cellular events, including intestinal cell survival, growth, differentiation, and apoptosis. A significant body of knowledge demonstrates that intestinal sphingolipids play a crucial role, as such and through their signaling pathways, in immunity and inflammatory disorders. In this review, we report on and discuss the current knowledge on the metabolism, signaling, and functional implications of sphingolipids in inflammatory bowel disease (IBD), focusing on the different aspects of sphingolipid actions on inflammatory responses and on the potential of sphingolipid-targeted molecules as anti-IBD therapeutic agents.

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