scholarly journals The Polycomb Orthologues in Teleost Fishes and Their Expression in the Zebrafish Model

Genes ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 362
Author(s):  
Ludivine Raby ◽  
Pamela Völkel ◽  
Xuefen Le Bourhis ◽  
Pierre-Olivier Angrand
Keyword(s):  
Transcriptional Repression ◽  
Cell Biology ◽  
Global Analysis ◽  
Mutual Exclusion ◽  
Protein Family ◽  
Specific Gene ◽  
Cellular Functions ◽  
Zebrafish Model ◽  
Vertebrate Model ◽  
Development And Differentiation

The Polycomb Repressive Complex 1 (PRC1) is a chromatin-associated protein complex involved in transcriptional repression of hundreds of genes controlling development and differentiation processes, but also involved in cancer and stem cell biology. Within the canonical PRC1, members of Pc/CBX protein family are responsible for the targeting of the complex to specific gene loci. In mammals, the Pc/CBX protein family is composed of five members generating, through mutual exclusion, different PRC1 complexes with potentially distinct cellular functions. Here, we performed a global analysis of the cbx gene family in 68 teleost species and traced the distribution of the cbx genes through teleost evolution in six fish super-orders. We showed that after the teleost-specific whole genome duplication, cbx4, cbx7 and cbx8 are retained as pairs of ohnologues. In contrast, cbx2 and cbx6 are present as pairs of ohnologues in the genome of several teleost clades but as singletons in others. Furthermore, since zebrafish is a widely used vertebrate model for studying development, we report on the expression of the cbx family members during zebrafish development and in adult tissues. We showed that all cbx genes are ubiquitously expressed with some variations during early development.

scholarly journals Novel roles for mammalian septins: from vesicle trafficking to oncogenesis

2001 ◽  
Vol 114 (5) ◽  
pp. 839-844 ◽  
Author(s):  
B. Kartmann ◽  
D. Roth
Keyword(s):  
Plasma Membrane ◽  
Recent Work ◽  
Cell Biology ◽  
Vesicle Trafficking ◽  
Family Members ◽  
Protein Family ◽  
Cellular Functions ◽  
Cellular Processes ◽  
Sequence Homologies ◽  
Genome Analyses

In recent years a convergence of various aspects of cell biology has become apparent, and yet investigators are only beginning to grasp the underlying unifying mechanisms. Among the proteins that participate in diverse aspects of cell biology are the septins. These are a group of novel GTPase proteins that are broadly distributed in many eukaryotes except plants. Although septins were originally identified as a protein family involved in cytokinesis in yeast, recent advances in the field have now ascribed additional functions to these proteins. In particular, the number of known mammalian septin family members has increased dramatically as more data has become available through genome analyses. We suggest a classification for the mammalian septins based on the sequence homologies in their highly divergent N- and C-termini. Recent work suggests novel functions for septins in vesicle trafficking, oncogenesis and compartmentalization of the plasma membrane. Given the ability of the septins to bind GTP and phosphatidylinositol 4,5-bisphosphate in a mutually exclusive manner, these proteins might be crucial elements for the spatial and/or temporal control of diverse cellular functions. As the functions of the septins become unraveled, our understanding of seemingly different cellular processes may move a step further.

scholarly journals The Multiple Faces of MNT and Its Role as a MYC Modulator

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4682
Author(s):  
Judit Liaño-Pons ◽  
Marie Arsenian-Henriksson ◽  
Javier León
Keyword(s):  
Cell Proliferation ◽  
Transcriptional Repression ◽  
Cell Biology ◽  
Essential Role ◽  
Present Knowledge ◽  
Special Focus ◽  
Cellular Functions ◽  
Cellular Processes ◽  
Tumor Cell Survival

MNT is a crucial modulator of MYC, controls several cellular functions, and is activated in most human cancers. It is the largest, most divergent, and most ubiquitously expressed protein of the MXD family. MNT was first described as a MYC antagonist and tumor suppressor. Indeed, 10% of human tumors present deletions of one MNT allele. However, some reports show that MNT functions in cooperation with MYC by maintaining cell proliferation, promoting tumor cell survival, and supporting MYC-driven tumorigenesis in cellular and animal models. Although MAX was originally considered MNT’s obligate partner, our recent findings demonstrate that MNT also works independently. MNT forms homodimers and interacts with proteins both outside and inside of the proximal MYC network. These complexes are involved in a wide array of cellular processes, from transcriptional repression via SIN3 to the modulation of metabolism through MLX as well as immunity and apoptosis via REL. In this review, we discuss the present knowledge of MNT with a special focus on its interactome, which sheds light on the complex and essential role of MNT in cell biology.

scholarly journals Zebrafish Model in Ophthalmology to Study Disease Mechanism and Drug Discovery

2021 ◽  
Vol 14 (8) ◽  
pp. 716
Author(s):  
Yiwen Hong ◽  
Yan Luo
Keyword(s):  
Drug Discovery ◽  
Behavioral Assessment ◽  
Age Related Macular Degeneration ◽  
Disease Mechanism ◽  
Zebrafish Model ◽  
Age Related ◽  
Eye Disorders ◽  
Vertebrate Model ◽  
Drug Treatments ◽  
Novel Drug

Visual impairment and blindness are common and seriously affect people’s work and quality of life in the world. Therefore, the effective therapies for eye diseases are of high priority. Zebrafish (Danio rerio) is an alternative vertebrate model as a useful tool for the mechanism elucidation and drug discovery of various eye disorders, such as cataracts, glaucoma, diabetic retinopathy, age-related macular degeneration, photoreceptor degeneration, etc. The genetic and embryonic accessibility of zebrafish in combination with a behavioral assessment of visual function has made it a very popular model in ophthalmology. Zebrafish has also been widely used in ocular drug discovery, such as the screening of new anti-angiogenic compounds or neuroprotective drugs, and the oculotoxicity test. In this review, we summarized the applications of zebrafish as the models of eye disorders to study disease mechanism and investigate novel drug treatments.

scholarly journals A journey from reductionist to systemic cell biology aboard the schooner Tara

2012 ◽  
Vol 23 (13) ◽  
pp. 2403-2406 ◽  
Author(s):  
Eric Karsenti
Keyword(s):  
Complex Systems ◽  
Molecular Interactions ◽  
Cell Biology ◽  
Statistical Physics ◽  
Interaction Networks ◽  
Cellular Functions ◽  
Personal Journey ◽  
New Approaches ◽  
The World ◽  
The Way

In this essay I describe my personal journey from reductionist to systems cell biology and describe how this in turn led to a 3-year sea voyage to explore complex ocean communities. In describing this journey, I hope to convey some important principles that I gleaned along the way. I realized that cellular functions emerge from multiple molecular interactions and that new approaches borrowed from statistical physics are required to understand the emergence of such complex systems. Then I wondered how such interaction networks developed during evolution. Because life first evolved in the oceans, it became a natural thing to start looking at the small organisms that compose the plankton in the world's oceans, of which 98% are … individual cells—hence the Tara Oceans voyage, which finished on 31 March 2012 in Lorient, France, after a 60,000-mile around-the-world journey that collected more than 30,000 samples from 153 sampling stations.

PI(4,5)P2 Clustering and Its Impact on Biological Functions

2021 ◽  
Vol 90 (1) ◽  
Author(s):  
Yi Wen ◽  
Volker M. Vogt ◽  
Gerald W. Feigenson
Keyword(s):  
Plasma Membrane ◽  
Cell Biology ◽  
Cellular Proteins ◽  
Annual Review ◽  
Publication Date ◽  
Biological Functions ◽  
Cellular Functions ◽  
Dynamic Distribution ◽  
Multivalent Cation ◽  
Lipid Environment

Located at the inner leaflet of the plasma membrane, phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] comprises only 1–2 mol% of total PM lipids. With its synthesis and turnover both spatially and temporally regulated, PI(4,5)P2 recruits and interacts with hundreds of cellular proteins to support a broad spectrum of cellular functions. Several factors contribute to the versatile and dynamic distribution of PI(4,5)P2 in membranes. Physiological multivalent cations such as Ca2+ and Mg2+ can bridge between PI(4,5)P2 headgroups, forming nanoscopic PI(4,5)P2–cation clusters. The distinct lipid environment surrounding PI(4,5)P2 affects the degree of PI(4,5)P2 clustering. In addition, diverse cellular proteins interacting with PI(4,5)P2 can further regulate PI(4,5)P2 lateral distribution and accessibility. This review summarizes the current understanding of PI(4,5)P2 behavior in both cells and model membranes, with emphasis on both multivalent cation– and protein-induced PI(4,5)P2 clustering. Understanding the nature of spatially separated pools of PI(4,5)P2 is fundamental to cell biology. Expected final online publication date for the Annual Review of Biochemistry, Volume 90 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Tumor-Progressive Mechanisms Mediating miRNA–Protein Interaction

2021 ◽  
Vol 22 (22) ◽  
pp. 12303
Author(s):  
Hiroaki Konishi ◽  
Hiroki Sato ◽  
Kenji Takahashi ◽  
Mikihiro Fujiya
Keyword(s):  
Cancer Progression ◽  
Regulatory System ◽  
Mrna Translation ◽  
Cellular Protein ◽  
Clinical Applications ◽  
Cancer Prognosis ◽  
Cellular Functions ◽  
Previous Decade ◽  
Extracellular Mirnas ◽  
Development And Differentiation

MicroRNAs (miRNAs) are single-stranded short-chain RNAs that are endogenously expressed in vertebrates; they are considered the fine-tuners of cellular protein expression that act by modifying mRNA translation. miRNAs control tissue development and differentiation, cell growth, and apoptosis in cancer and non-cancer cells. Aberrant regulation of miRNAs is involved in the pathogenesis of various diseases including cancer. Numerous investigations have shown that the changes in cellular miRNA expression in cancerous tissues and extracellular miRNAs enclosed in exosomes are correlated with cancer prognosis. Therefore, miRNAs can be used as cancer biomarkers and therapeutic targets for cancer in clinical applications. In the previous decade, miRNAs have been shown to regulate cellular functions by directly binding to proteins and mRNAs, thereby controlling cancer progression. This regulatory system implies that cancer-associated miRNAs can be applied as molecular-targeted therapy. This review discusses the roles of miRNA–protein systems in cancer progression and its future applications in cancer treatment.

scholarly journals Cytochemical methods for the localization of adenylate cyclase. A review and evaluation of the efficacy of the procedures.

1983 ◽  
Vol 31 (1) ◽  
pp. 85-93 ◽  
Author(s):  
L S Cutler
Keyword(s):  
Adenylate Cyclase ◽  
Cyclic Nucleotides ◽  
Cell Biology ◽  
Enzyme System ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Cellular Functions ◽  
Cytochemical Localization ◽  
Biochemical Evaluation

The cytochemical procedures for localizing adenylate cyclase have been a source of controversy since their introduction. The importance of cyclic adenosine monophosphate (AMP), the product of adenylate cyclase's action on adenosine triphosphate (ATP), in cell biology is clear. Thus, the ability to localize this enzyme system reliably is an important tool in the study of various cellular functions. This report reviews the literature and presents a biochemical evaluation of the methods for localizing adenylate cyclase. The review and data presented serve to clarify many of the controversies surrounding this important cytochemical procedure. It is evident that although there are problems associated with localizing the enzyme, several valid procedures are currently available for the cytochemical localization of adenylate cyclase. In using these procedures, the effects of fixation and the capture agent on adenylate cyclase activity in the particular tissue being studied should be considered. Only repurified adenylyl imidodiphosphate [App(NH)p] should be used in the incubation medium. If care is taken, the use of these techniques can be of great value in the continued study of the role of cyclic nucleotides in cell biology.

scholarly journals MyoR Modulates Cardiac Conduction by Repressing Gata4

2014 ◽  
Vol 35 (4) ◽  
pp. 649-661 ◽  
Author(s):  
John P. Harris ◽  
Minoti Bhakta ◽  
Svetlana Bezprozvannaya ◽  
Lin Wang ◽  
Christina Lubczyk ◽  
...  
Keyword(s):  
Transcriptional Repression ◽  
Atrioventricular Node ◽  
Electrical Activation ◽  
Cardiac Conduction ◽  
Specific Gene ◽  
Dependent Manner ◽  
Regulatory Circuit ◽  
Genetic Deletion ◽  
Repression Domain ◽  
Av Delay

The cardiac conduction system coordinates electrical activation through a series of interconnected structures, including the atrioventricular node (AVN), the central connection point that delays impulse propagation to optimize cardiac performance. Although recent studies have uncovered important molecular details of AVN formation, relatively little is known about the transcriptional mechanisms that regulate AV delay, the primary function of the mature AVN. We identify here MyoR as a novel transcription factor expressed in Cx30.2+cells of the AVN. We show that MyoR specifically inhibits a Cx30.2 enhancer required for AVN-specific gene expression. Furthermore, we demonstrate that MyoR interacts directly with Gata4 to mediate transcriptional repression. Our studies reveal that MyoR contains two nonequivalent repression domains. While the MyoR C-terminal repression domain inhibits transcription in a context-dependent manner, the N-terminal repression domain can function in a heterologous context to convert the Hand2 activator into a repressor. In addition, we show that genetic deletion of MyoR in mice increases Cx30.2 expression by 50% and prolongs AV delay by 13%. Taken together, we conclude that MyoR modulates a Gata4-dependent regulatory circuit that establishes proper AV delay, and these findings may have wider implications for the variability of cardiac rhythm observed in the general population.

scholarly journals Eukaryotic systems broaden the scope of synthetic biology

2009 ◽  
Vol 187 (5) ◽  
pp. 589-596 ◽  
Author(s):  
Karmella A. Haynes ◽  
Pamela A. Silver
Keyword(s):  
Synthetic Biology ◽  
Nucleic Acids ◽  
Cell Biology ◽  
Cell Behavior ◽  
Cellular Functions ◽  
Complex Cells ◽  
Cellular Processes ◽  
Challenges And Opportunities ◽  
Foundational Work ◽  
Biology Research

Synthetic biology aims to engineer novel cellular functions by assembling well-characterized molecular parts (i.e., nucleic acids and proteins) into biological “devices” that exhibit predictable behavior. Recently, efforts in eukaryotic synthetic biology have sprung from foundational work in bacteria. Designing synthetic circuits to operate reliably in the context of differentiating and morphologically complex cells presents unique challenges and opportunities for progress in the field. This review surveys recent advances in eukaryotic synthetic biology and describes how synthetic systems can be linked to natural cellular processes in order to manipulate cell behavior and to foster new discoveries in cell biology research.

A repressor controls the timing and spatial localisation of stalk cell-specific gene expression in Dictyostelium

Development ◽  
1993 ◽  
Vol 118 (4) ◽  
pp. 1041-1048 ◽  
Author(s):  
A.J. Harwood ◽  
A. Early ◽  
J.G. Williams
Keyword(s):  
Gene Expression ◽  
Transcriptional Repression ◽  
Consensus Sequence ◽  
Matrix Proteins ◽  
Stalk Cell ◽  
Specific Gene ◽  
Gene Mutant ◽  
Dependent Protein ◽  
Apical Papilla ◽  
Repressor Element

The ecmA and ecmB genes of Dictyostelium encode related extracellular matrix proteins and both are induced by DIF, the stalk cell-specific morphogen. The ecmA gene is expressed throughout the prestalk region of the migrating slug but only later, at culmination, do the prestalk cells express the ecmB gene. Expression of the ecmB gene is induced at the entrance to the stalk tube and we have identified two, apparently redundant, promoter elements that control this process. They act as repressors, preventing transcription in the tip of the migrating slug and the apical papilla of the culminant. They have a semi-palindromic consensus sequence TTGnCAA, where n is in one case 2 and in the other 4 bp. Either element alone is able to repress ecmB promoter activity in prestalk cells. Introduction of a single repressor element into the promoter of the ecmA gene changes its expression pattern to resemble that of the ecmB gene. Mutant elements, where n is altered, cause repression during the slug stage but allow premature ecmB expression during culmination; suggesting that the effective strength of the inductive signal may increase during culmination. Inhibition of cAMP-dependent protein kinase (PKA) in prestalk cells blocks both stalk cell maturation and ecmB gene expression. We show that the block to gene expression correlates precisely with the presence of a functional repressor element and this is consistent with the notion that expression of the ecmB gene is controlled by a PKA-dependent release from transcriptional repression.

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