scholarly journals New Insights into Cellular Functions of Nuclear Actin

Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 304
Author(s):  
Malgorzata Kloc ◽  
Priyanka Chanana ◽  
Nicole Vaughn ◽  
Ahmed Uosef ◽  
Jacek Z. Kubiak ◽  
...  

Actin is one of the most abundant proteins in eukaryotic cells. There are different pools of nuclear actin often undetectable by conventional staining and commercial antibodies used to identify cytoplasmic actin. With the development of more sophisticated imaging and analytical techniques, it became clear that nuclear actin plays a crucial role in shaping the chromatin, genomic, and epigenetic landscape, transcriptional regulation, and DNA repair. This multifaceted role of nuclear actin is not only important for the function of the individual cell but also for the establishment of cell fate, and tissue and organ differentiation during development. Moreover, the changes in the nuclear, chromatin, and genomic architecture are preamble to various diseases. Here, we discuss some of the newly described functions of nuclear actin.

2005 ◽  
Vol 391 (2) ◽  
pp. 417-424 ◽  
Author(s):  
Victor H. Bustos ◽  
Oriano Marin ◽  
Flavio Meggio ◽  
Luca Cesaro ◽  
Catherine C. Allende ◽  
...  

Protein kinase CK1 denotes a family of pleiotropic serine/threonine protein kinases implicated in a variety of cellular functions. Typically, CK1 acts as a ‘phosphate-directed’ kinase whose targeting is primed by a single phosphorylated side chain at position n−3 or n−4 relative to serine/threonine, but increasing evidence is accumulating that CK1 can also engage some of its substrates at sites that do not conform to this canonical consensus. In the present paper, we show that CK1α phosphorylates with the same efficiency phosphopeptides primed by a phosphoserine residue at either n−3 [pS(−3)] or n−4 [pS(−4)] positions. The phosphorylation efficiency of the pS(−4) peptide, and to a lesser extent that of the pS(−3) peptide, is impaired by the triple mutation of the lysine residues in the K229KQK232 stretch to alanine residues, promoting 40-fold and 6-fold increases of Km respectively. In both cases, the individual mutation of Lys232 is as detrimental as the triple mutation. A kinetic alanine-scan analysis with a series of substituted peptide substrates in which the priming phosphoserine residue was effectively replaced by a cluster of four aspartate residues was also consistent with a crucial role of Lys232 in the recognition of the acidic determinant at position n−4. In sharp contrast, the phosphorylation of β-catenin and of a peptide including the non-canonical β-catenin site (Ser45) lacking acidic/phosphorylated determinants upstream is not significantly affected by mutations in the KKQK stretch. These data provide a molecular insight into the structural features that underlie the site specificity of CK1α and disclose the possibility of developing strategies for the preferential targeting of subsets of CK1 substrates.


2006 ◽  
Vol 34 (5) ◽  
pp. 722-726 ◽  
Author(s):  
E.W.-F. Lam ◽  
R.E. Francis ◽  
M. Petkovic

FOXO (forkhead box O) transcription factors are crucial regulators of cell fate. This function of FOXO proteins relies on their ability to control diverse and at times, opposing cellular functions, such as proliferation, differentiation, DNA repair, defence against oxidative stress damage and apoptosis, in response to hormones, growth factors and other environmental cues. This review discusses our current understanding of the regulation and role of FOXO transcription factors in determining cell fate and highlights their relevance to tumorigenesis and drug resistance.


2021 ◽  
Vol 22 (10) ◽  
pp. 5209
Author(s):  
Stine F. Pedersen ◽  
Mette Flinck ◽  
Luis A. Pardo

Transport of ions and nutrients is a core mitochondrial function, without which there would be no mitochondrial metabolism and ATP production. Both ion homeostasis and mitochondrial phenotype undergo pervasive changes during cancer development, and both play key roles in driving the malignancy. However, the link between these events has been largely ignored. This review comprehensively summarizes and critically discusses the role of the reciprocal relationship between ion transport and mitochondria in crucial cellular functions, including metabolism, signaling, and cell fate decisions. We focus on Ca2+, H+, and K+, which play essential and highly interconnected roles in mitochondrial function and are profoundly dysregulated in cancer. We describe the transport and roles of these ions in normal mitochondria, summarize the changes occurring during cancer development, and discuss how they might impact tumorigenesis.


Blood ◽  
2006 ◽  
Vol 107 (6) ◽  
pp. 2223-2233 ◽  
Author(s):  
Kevin G. Leong ◽  
Aly Karsan

AbstractMembers of the Notch family of transmembrane receptors play an important role in cell fate determination. Over the past decade, a role for Notch in the pathogenesis of hematologic and solid malignancies has become apparent. Numerous cellular functions and microenvironmental cues associated with tumorigenesis are modulated by Notch signaling, including proliferation, apoptosis, adhesion, epithelial-to-mesenchymal transition, and angiogenesis. It is becoming increasingly evident that Notch signaling can be both oncogenic and tumor suppressive. This review highlights recent findings regarding the molecular and functional aspects of Notch-mediated neoplastic transformation. In addition, cellular mechanisms that potentially explain the complex role of Notch in tumorigenesis are discussed.


2008 ◽  
Vol 389 (3) ◽  
pp. 279-283 ◽  
Author(s):  
Daniel G. Sedding

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.


2021 ◽  
Author(s):  
Marta Urbanska ◽  
Yan Ge ◽  
Maria Winzi ◽  
Shada Abuhattum ◽  
Maik Herbig ◽  
...  

AbstractMechanical proprieties determine many cellular functions, such as cell fate specification, migration, or circulation through vasculature. Identifying factors governing cell mechanical phenotype is therefore a subject of great interest. Here we present a mechanomics approach for establishing links between mechanical phenotype changes and the genes involved in driving them. We employ a machine learning-based discriminative network analysis method termed PC-corr to associate cell mechanical states, measured by real-time deformability cytometry (RT-DC), with large-scale transcriptome datasets ranging from stem cell development to cancer progression, and originating from different murine and human tissues. By intersecting the discriminative networks inferred from two selected datasets, we identify a conserved module of five genes with putative roles in the regulation of cell mechanics. We validate the power of the individual genes to discriminate between soft and stiff cell states in silico, and demonstrate experimentally that the top scoring gene, CAV1, changes the mechanical phenotype of cells when silenced or overexpressed. The data-driven approach presented here has the power of de novo identification of genes involved in cell mechanics regulation and paves the way towards engineering cell mechanical properties on demand to explore their impact on physiological and pathological cell functions.


2020 ◽  
Vol 48 (3) ◽  
pp. 1243-1253 ◽  
Author(s):  
Sukriti Kapoor ◽  
Sachin Kotak

Cellular asymmetries are vital for generating cell fate diversity during development and in stem cells. In the newly fertilized Caenorhabditis elegans embryo, centrosomes are responsible for polarity establishment, i.e. anterior–posterior body axis formation. The signal for polarity originates from the centrosomes and is transmitted to the cell cortex, where it disassembles the actomyosin network. This event leads to symmetry breaking and the establishment of distinct domains of evolutionarily conserved PAR proteins. However, the identity of an essential component that localizes to the centrosomes and promotes symmetry breaking was unknown. Recent work has uncovered that the loss of Aurora A kinase (AIR-1 in C. elegans and hereafter referred to as Aurora A) in the one-cell embryo disrupts stereotypical actomyosin-based cortical flows that occur at the time of polarity establishment. This misregulation of actomyosin flow dynamics results in the occurrence of two polarity axes. Notably, the role of Aurora A in ensuring a single polarity axis is independent of its well-established function in centrosome maturation. The mechanism by which Aurora A directs symmetry breaking is likely through direct regulation of Rho-dependent contractility. In this mini-review, we will discuss the unconventional role of Aurora A kinase in polarity establishment in C. elegans embryos and propose a refined model of centrosome-dependent symmetry breaking.


2013 ◽  
Vol 18 (2) ◽  
pp. 126-135 ◽  
Author(s):  
Frosso Motti-Stefanidi ◽  
Ann S. Masten

Academic achievement in immigrant children and adolescents is an indicator of current and future adaptive success. Since the future of immigrant youths is inextricably linked to that of the receiving society, the success of their trajectory through school becomes a high stakes issue both for the individual and society. The present article focuses on school success in immigrant children and adolescents, and the role of school engagement in accounting for individual and group differences in academic achievement from the perspective of a multilevel integrative model of immigrant youths’ adaptation ( Motti-Stefanidi, Berry, Chryssochoou, Sam, & Phinney, 2012 ). Drawing on this conceptual framework, school success is examined in developmental and acculturative context, taking into account multiple levels of analysis. Findings suggest that for both immigrant and nonimmigrant youths the relationship between school engagement and school success is bidirectional, each influencing over time the other. Evidence regarding potential moderating and mediating roles of school engagement for the academic success of immigrant youths also is evaluated.


Acta Naturae ◽  
2016 ◽  
Vol 8 (2) ◽  
pp. 79-86 ◽  
Author(s):  
P. V. Elizar’ev ◽  
D. V. Lomaev ◽  
D. A. Chetverina ◽  
P. G. Georgiev ◽  
M. M. Erokhin

Maintenance of the individual patterns of gene expression in different cell types is required for the differentiation and development of multicellular organisms. Expression of many genes is controlled by Polycomb (PcG) and Trithorax (TrxG) group proteins that act through association with chromatin. PcG/TrxG are assembled on the DNA sequences termed PREs (Polycomb Response Elements), the activity of which can be modulated and switched from repression to activation. In this study, we analyzed the influence of transcriptional read-through on PRE activity switch mediated by the yeast activator GAL4. We show that a transcription terminator inserted between the promoter and PRE doesnt prevent switching of PRE activity from repression to activation. We demonstrate that, independently of PRE orientation, high levels of transcription fail to dislodge PcG/TrxG proteins from PRE in the absence of a terminator. Thus, transcription is not the main factor required for PRE activity switch.


2019 ◽  
pp. 22-29
Author(s):  
Н. В. Фрадкіна

The purpose and tasks of the work are to analyze the contemporary Ukrainian mass culture in terms of its value and humanistic components, as well as the importance of cultural studies and Ukrainian studies in educational disciplines for the formation of a holistic worldview of modern youth.Analysis of research and publications. Scientists repeatedly turned to the problems of the role of spirituality in the formation of society and its culture. This problem is highlighted in the publications by O. Losev, V. Lytvyn, D. Likhachev, S. Avierintsev, M. Zakovych, I. Stepanenko and E. Kostyshyn.Experts see the main negative impact of mass culture on the quality approach, which determines mass culture through the market, because mass culture, from our point of view, is everything that is sold and used in mass demand.One of the most interesting studies on this issue was the work by the representatives of Frankfurt School M. Horkheimer and T. Adorno «Dialectics of Enlightenment» (1947), devoted to a detailed analysis of mass culture. Propaganda at all socio-cultural levels in the form is similar in both totalitarian and democratic countries. It is connected, according to the authors, with the direction of European enlightenment. The tendency to unify people is a manifestation of the influence of mass culture, from cinema to pop. Mass culture is a phenomenon whose existence is associated with commerce (accumulation in any form – this is the main feature of education), in general, the fact that it exists in this form is related to the direction of the history of civilization.Modern mass culture, with its externally attractive and easily assimilated ideas and symbols, appealing to the trends of modern fashion, becomes a standard of prestigious consumption, does not require intense reflection, allows you to relax, distract, not teach, but entertains, preaches hedonism as the main spiritual value. And as a consequence, there are socio-cultural risks: an active rejection of other people, which leads to the formation of indifference; cruelty as a character trait; increase of violent and mercenary crime; increase in the number of alcohol and drug addicts; anti-patriotism; indifference to the values of the family and as a result of social orphanhood and prostitution.Conclusions, perspectives of research. Thus, we can conclude that modern Ukrainian education is predominantly formed by the values of mass culture. Namely, according to the «Dialectic» by Horkheimer and Adorno, «semi-enlightenment becomes an objective spirit» of our modern society.It is concluded that only high-quality education can create the opposite of the onset of mass culture and the destruction of spirituality in our society. It is proved that only by realizing the importance of cultivating disciplines in the educational process and the spiritual upbringing of the nation, through educational reforms, humanitarian knowledge will gradually return to student audiences.Formation of youth occurs under the influence of social environment, culture, education and self-education. The optimal combination of these factors determines both the process of socialization itself and how successful it will be. In this context, one can see the leading role of education and upbringing. It turns out that the main task of modern education is to spread its influence on the development of spiritual culture of the individual, which eventually becomes a solid foundation for the formation of the individual. Such a subject requires both philosophical and humanitarian approaches in further integrated interdisciplinary research, since the availability of such research will provide the theoretical foundation for truly modern educational and personal development.


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