Recent Developments in the Theory of Control and Regulation of Cellular Processes

Author(s):  
Robert Rosen
Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3606
Author(s):  
Samuel P. Boyson ◽  
Cong Gao ◽  
Kathleen Quinn ◽  
Joseph Boyd ◽  
Hana Paculova ◽  
...  

Histone acetylation is generally associated with an open chromatin configuration that facilitates many cellular processes including gene transcription, DNA repair, and DNA replication. Aberrant levels of histone lysine acetylation are associated with the development of cancer. Bromodomains represent a family of structurally well-characterized effector domains that recognize acetylated lysines in chromatin. As part of their fundamental reader activity, bromodomain-containing proteins play versatile roles in epigenetic regulation, and additional functional modules are often present in the same protein, or through the assembly of larger enzymatic complexes. Dysregulated gene expression, chromosomal translocations, and/or mutations in bromodomain-containing proteins have been correlated with poor patient outcomes in cancer. Thus, bromodomains have emerged as a highly tractable class of epigenetic targets due to their well-defined structural domains, and the increasing ease of designing or screening for molecules that modulate the reading process. Recent developments in pharmacological agents that target specific bromodomains has helped to understand the diverse mechanisms that bromodomains play with their interaction partners in a variety of chromatin processes, and provide the promise of applying bromodomain inhibitors into the clinical field of cancer treatment. In this review, we explore the expression and protein interactome profiles of bromodomain-containing proteins and discuss them in terms of functional groups. Furthermore, we highlight our current understanding of the roles of bromodomain-containing proteins in cancer, as well as emerging strategies to specifically target bromodomains, including combination therapies using bromodomain inhibitors alongside traditional therapeutic approaches designed to re-program tumorigenesis and metastasis.


2016 ◽  
Vol 113 (52) ◽  
pp. 15060-15065 ◽  
Author(s):  
Niels G. A. Kuijpers ◽  
Daniel Solis-Escalante ◽  
Marijke A. H. Luttik ◽  
Markus M. M. Bisschops ◽  
Francine J. Boonekamp ◽  
...  

Recent developments in synthetic biology enable one-step implementation of entire metabolic pathways in industrial microorganisms. A similarly radical remodelling of central metabolism could greatly accelerate fundamental and applied research, but is impeded by the mosaic organization of microbial genomes. To eliminate this limitation, we propose and explore the concept of “pathway swapping,” using yeast glycolysis as the experimental model. Construction of a “single-locus glycolysis” Saccharomyces cerevisiae platform enabled quick and easy replacement of this yeast’s entire complement of 26 glycolytic isoenzymes by any alternative, functional glycolytic pathway configuration. The potential of this approach was demonstrated by the construction and characterization of S. cerevisiae strains whose growth depended on two nonnative glycolytic pathways: a complete glycolysis from the related yeast Saccharomyces kudriavzevii and a mosaic glycolysis consisting of yeast and human enzymes. This work demonstrates the feasibility and potential of modular, combinatorial approaches to engineering and analysis of core cellular processes.


Genes ◽  
2020 ◽  
Vol 11 (10) ◽  
pp. 1163
Author(s):  
Sebastian L. Wild ◽  
Aya Elghajiji ◽  
Carmen Grimaldos Rodriguez ◽  
Stephen D. Weston ◽  
Zoë D. Burke ◽  
...  

The canonical Wnt (Wnt/β-catenin) signalling pathway is highly conserved and plays a critical role in regulating cellular processes both during development and in adult tissue homeostasis. The Wnt/β-catenin signalling pathway is vital for correct body patterning and is involved in fate specification of the gut tube, the primitive precursor of liver. In adults, the Wnt/β-catenin pathway is increasingly recognised as an important regulator of metabolic zonation, homeostatic renewal and regeneration in response to injury throughout the liver. Herein, we review recent developments relating to the key role of the pathway in the patterning and fate specification of the liver, in the directed differentiation of pluripotent stem cells into hepatocytes and in governing proliferation and zonation in the adult liver. We pay particular attention to recent contributions to the controversy surrounding homeostatic renewal and proliferation in response to injury. Furthermore, we discuss how crosstalk between the Wnt/β-catenin and Hedgehog (Hh) and hypoxia inducible factor (HIF) pathways works to maintain liver homeostasis. Advancing our understanding of this pathway will benefit our ability to model disease, screen drugs and generate tissue and organ replacements for regenerative medicine.


F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1676 ◽  
Author(s):  
Andrew B. Goryachev ◽  
Marcin Leda

Small GTPases are organizers of a plethora of cellular processes. The time and place of their activation are tightly controlled by the localization and activation of their regulators, guanine-nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Remarkably, in some systems, the upstream regulators of GTPases are also found downstream of their activity. Resulting feedback loops can generate complex spatiotemporal dynamics of GTPases with important functional consequences. Here we discuss the concept of positive autoregulation of small GTPases by the GEF–effector feedback modules and survey recent developments in this exciting area of cell biology.


2013 ◽  
Vol 368 (1611) ◽  
pp. 20120024 ◽  
Author(s):  
Hendrik Sielaff ◽  
Michael Börsch

F O F 1 -ATP synthases are ubiquitous proton- or ion-powered membrane enzymes providing ATP for all kinds of cellular processes. The mechanochemistry of catalysis is driven by two rotary nanomotors coupled within the enzyme. Their different step sizes have been observed by single-molecule microscopy including videomicroscopy of fluctuating nanobeads attached to single enzymes and single-molecule Förster resonance energy transfer. Here we review recent developments of approaches to monitor the step size of subunit rotation and the transient elastic energy storage mechanism in single F O F 1 -ATP synthases.


IUCrJ ◽  
2014 ◽  
Vol 1 (6) ◽  
pp. 470-477 ◽  
Author(s):  
Nicholas J. Brooks

Membranes are amongst the most important biological structures; they maintain the fundamental integrity of cells, compartmentalize regions within them and play an active role in a wide range of cellular processes. Pressure can play a key role in probing the structure and dynamics of membrane assemblies, and is also critical to the biology and adaptation of deep-sea organisms. This article presents an overview of the effect of pressure on the mesostructure of lipid membranes, bilayer organization and lipid–protein assemblies. It also summarizes recent developments in high-pressure structural instrumentation suitable for experiments on membranes.


2021 ◽  
Vol 7 (1) ◽  
pp. 65
Author(s):  
Kongara Hanumantha Rao ◽  
Soumita Paul ◽  
Swagata Ghosh

The amino sugar, N-acetylglucosamine (GlcNAc), has emerged as an attractive messenger of signaling in the pathogenic yeast Candida albicans, given its multifaceted role in cellular processes, including GlcNAc scavenging, import and metabolism, morphogenesis (yeast to hyphae and white to opaque switch), virulence, GlcNAc induced cell death (GICD), etc. During signaling, the exogenous GlcNAc appears to adopt a simple mechanism of gene regulation by directly activating Ngs1, a novel GlcNAc sensor and transducer, at the chromatin level, to activate transcriptional response through the promoter acetylation. Ngs1 acts as a master regulator in GlcNAc signaling by regulating GlcNAc catabolic gene expression and filamentation. Ndt80-family transcriptional factor Rep1 appears to be involved in the recruitment of Ngs1 to GlcNAc catabolic gene promoters. For promoting filamentation, GlcNAc adopts a little modified strategy by utilizing a recently evolved transcriptional loop. Here, Biofilm regulator Brg1 takes up the key role, getting up-regulated by Ngs1, and simultaneously induces Hyphal Specific Genes (HSGs) expression by down-regulating NRG1 expression. GlcNAc kinase Hxk1 appears to play a prominent role in signaling. Recent developments in GlcNAc signaling have made C. albicans a model system to understand its role in other eukaryotes as well. The knowledge thus gained would assist in designing therapeutic interventions for the control of candidiasis and other fungal diseases.


2020 ◽  
Vol 19 ◽  
pp. 153601212098151
Author(s):  
Mucong Li ◽  
Nikhila Nyayapathi ◽  
Hailey I. Kilian ◽  
Jun Xia ◽  
Jonathan F. Lovell ◽  
...  

Photoacoustic tomography (PAT) has become increasingly popular for molecular imaging due to its unique optical absorption contrast, high spatial resolution, deep imaging depth, and high imaging speed. Yet, the strong optical attenuation of biological tissues has traditionally prevented PAT from penetrating more than a few centimeters and limited its application for studying deeply seated targets. A variety of PAT technologies have been developed to extend the imaging depth, including employing deep-penetrating microwaves and X-ray photons as excitation sources, delivering the light to the inside of the organ, reshaping the light wavefront to better focus into scattering medium, as well as improving the sensitivity of ultrasonic transducers. At the same time, novel optical fluence mapping algorithms and image reconstruction methods have been developed to improve the quantitative accuracy of PAT, which is crucial to recover weak molecular signals at larger depths. The development of highly-absorbing near-infrared PA molecular probes has also flourished to provide high sensitivity and specificity in studying cellular processes. This review aims to introduce the recent developments in deep PA molecular imaging, including novel imaging systems, image processing methods and molecular probes, as well as their representative biomedical applications. Existing challenges and future directions are also discussed.


Author(s):  
Longxiang Xie ◽  
Yafei Xiao ◽  
Fucheng Meng ◽  
Yongqiang Li ◽  
Zhenyu Shi ◽  
...  

Lysine glutarylation (Kglu) is a newly discovered post-translational modification (PTM), which is considered to be reversible, dynamic, and conserved in prokaryotes and eukaryotes. Recent developments in the identification of Kglu by mass spectrometry have shown that Kglu is mainly involved in the regulation of metabolism, oxidative damage, chromatin dynamics and is associated with various diseases. In this review, we firstly summarize the development history of glutarylation, the biochemical processes of glutarylation and deglutarylation. Then we focus on the pathophysiological functions such as glutaric acidemia 1, asthenospermia, etc. Finally, the current computational tools for predicting glutarylation sites are discussed. These emerging findings point to new functions for lysine glutarylation and related enzymes, and also highlight the mechanisms by which glutarylation regulates diverse cellular processes.


2022 ◽  
Vol 18 (1) ◽  
pp. e1009762
Author(s):  
Yan Wu ◽  
Lingfeng Xue ◽  
Wen Huang ◽  
Minghua Deng ◽  
Yihan Lin

Activities of transcription factors (TFs) are temporally modulated to regulate dynamic cellular processes, including development, homeostasis, and disease. Recent developments of bioinformatic tools have enabled the analysis of TF activities using transcriptome data. However, because these methods typically use exon-based target expression levels, the estimated TF activities have limited temporal accuracy. To address this, we proposed a TF activity measure based on intron-level information in time-series RNA-seq data, and implemented it to decode the temporal control of TF activities during dynamic processes. We showed that TF activities inferred from intronic reads can better recapitulate instantaneous TF activities compared to the exon-based measure. By analyzing public and our own time-series transcriptome data, we found that intron-based TF activities improve the characterization of temporal phasing of cycling TFs during circadian rhythm, and facilitate the discovery of two temporally opposing TF modules during T cell activation. Collectively, we anticipate that the proposed approach would be broadly applicable for decoding global transcriptional architecture during dynamic processes.


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