The Regulatory Mechanisms of Cyanotoxin β-N-Methylamino-L-Alanine (BMAA) Action on the Key Cellular Processes in Diazotrophic Cyanobacteria

Rho GDP dissociation inhibitors (RhoGDIs) play important roles in various cellular processes, including cell migration, adhesion, and proliferation, by regulating the functions of the Rho GTPase family. Dissociation of Rho GTPases from RhoGDIs is necessary for their spatiotemporal activation and is dynamically regulated by several mechanisms, such as phosphorylation, sumoylation, and protein interaction. The expression of RhoGDIs has changed in many human cancers and become associated with the malignant phenotype, including migration, invasion, metastasis, and resistance to anticancer agents. Here, we review how RhoGDIs control the function of Rho GTPases by regulating their spatiotemporal activity and describe the regulatory mechanisms of the dissociation of Rho GTPases from RhoGDIs. We also discuss the role of RhoGDIs in cancer progression and their potential uses for therapeutic intervention.

Download Full-text

Tracking changes in adaptation to suspension growth for MDCK cells: cell growth correlates with levels of metabolites, enzymes and proteins

Applied Microbiology and Biotechnology ◽

10.1007/s00253-021-11150-z ◽

2021 ◽

Vol 105 (5) ◽

pp. 1861-1874

Author(s):

Sabine Pech ◽

Markus Rehberg ◽

Robert Janke ◽

Dirk Benndorf ◽

Yvonne Genzel ◽

...

Keyword(s):

Cell Growth ◽

Cell Line ◽

Mdck Cells ◽

Suspension Cell ◽

Regulatory Mechanisms ◽

Adherent Cell ◽

Holistic View ◽

Cellular Processes ◽

Viral Vaccine ◽

Analytical Approaches

Abstract Adaptations of animal cells to growth in suspension culture concern in particular viral vaccine production, where very specific aspects of virus-host cell interaction need to be taken into account to achieve high cell specific yields and overall process productivity. So far, the complexity of alterations on the metabolism, enzyme, and proteome level required for adaptation is only poorly understood. In this study, for the first time, we combined several complex analytical approaches with the aim to track cellular changes on different levels and to unravel interconnections and correlations. Therefore, a Madin-Darby canine kidney (MDCK) suspension cell line, adapted earlier to growth in suspension, was cultivated in a 1-L bioreactor. Cell concentrations and cell volumes, extracellular metabolite concentrations, and intracellular enzyme activities were determined. The experimental data set was used as the input for a segregated growth model that was already applied to describe the growth dynamics of the parental adherent cell line. In addition, the cellular proteome was analyzed by liquid chromatography coupled to tandem mass spectrometry using a label-free protein quantification method to unravel altered cellular processes for the suspension and the adherent cell line. Four regulatory mechanisms were identified as a response of the adaptation of adherent MDCK cells to growth in suspension. These regulatory mechanisms were linked to the proteins caveolin, cadherin-1, and pirin. Combining cell, metabolite, enzyme, and protein measurements with mathematical modeling generated a more holistic view on cellular processes involved in the adaptation of an adherent cell line to suspension growth. Key points • Less and more efficient glucose utilization for suspension cell growth • Concerted alteration of metabolic enzyme activity and protein expression • Protein candidates to interfere glycolytic activity in MDCK cells

Download Full-text

Unconventional Myosins: How Regulation Meets Function

International Journal of Molecular Sciences ◽

10.3390/ijms21010067 ◽

2019 ◽

Vol 21 (1) ◽

pp. 67 ◽

Cited By ~ 9

Author(s):

Natalia Fili ◽

Christopher P. Toseland

Keyword(s):

Molecular Motors ◽

Current Knowledge ◽

Local Environment ◽

Structural Features ◽

Regulatory Mechanisms ◽

Tight Control ◽

Cellular Processes ◽

Binding Partners ◽

Wide Range ◽

Multiple Levels

Unconventional myosins are multi-potent molecular motors that are assigned important roles in fundamental cellular processes. Depending on their mechano-enzymatic properties and structural features, myosins fulfil their roles by acting as cargo transporters along the actin cytoskeleton, molecular anchors or tension sensors. In order to perform such a wide range of roles and modes of action, myosins need to be under tight regulation in time and space. This is achieved at multiple levels through diverse regulatory mechanisms: the alternative splicing of various isoforms, the interaction with their binding partners, their phosphorylation, their applied load and the composition of their local environment, such as ions and lipids. This review summarizes our current knowledge of how unconventional myosins are regulated, how these regulatory mechanisms can adapt to the specific features of a myosin and how they can converge with each other in order to ensure the required tight control of their function.

Download Full-text

Advances in the role of m6A RNA modification in cancer metabolic reprogramming

Cell & Bioscience ◽

10.1186/s13578-020-00479-z ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Xiu Han ◽

Lin Wang ◽

Qingzhen Han

Keyword(s):

Cancer Cells ◽

Epigenetic Modification ◽

Metabolic Reprogramming ◽

Regulatory Mechanisms ◽

Rna Modification ◽

Biological Functions ◽

Rna Transcription ◽

Cellular Processes ◽

Metabolic Genes

Abstract N6-methyladenosine (m6A) modification is the most common internal modification of eukaryotic mRNA and is widely involved in many cellular processes, such as RNA transcription, splicing, nuclear transport, degradation, and translation. m6A has been shown to plays important roles in the initiation and progression of various cancers. The altered metabolic programming of cancer cells promotes their cell-autonomous proliferation and survival, leading to an indispensable hallmark of cancers. Accumulating evidence has demonstrated that this epigenetic modification exerts extensive effects on the cancer metabolic network by either directly regulating the expression of metabolic genes or modulating metabolism-associated signaling pathways. In this review, we summarized the regulatory mechanisms and biological functions of m6A and its role in cancer metabolic reprogramming.

Download Full-text

Functional Amyloids Are the Rule Rather Than the Exception in Cellular Biology

Microorganisms ◽

10.3390/microorganisms8121951 ◽

2020 ◽

Vol 8 (12) ◽

pp. 1951

Author(s):

Anthony Balistreri ◽

Emily Goetzler ◽

Matthew Chapman

Keyword(s):

Functional Role ◽

Cellular Systems ◽

Regulatory Mechanisms ◽

Cellular Biology ◽

Biological Functions ◽

Cellular Processes ◽

Domains Of Life ◽

Functional Amyloids ◽

Definition Of ◽

And Storage

Amyloids are a class of protein aggregates that have been historically characterized by their relationship with human disease. Indeed, amyloids can be the result of misfolded proteins that self-associate to form insoluble, extracellular plaques in diseased tissue. For the first 150 years of their study, the pathogen-first definition of amyloids was sufficient. However, new observations of amyloids foster an appreciation for non-pathological roles for amyloids in cellular systems. There is now evidence from all domains of life that amyloids can be non-pathogenic and functional, and that their formation can be the result of purposeful and controlled cellular processes. So-called functional amyloids fulfill an assortment of biological functions including acting as structural scaffolds, regulatory mechanisms, and storage mechanisms. The conceptual convergence of amyloids serving a functional role has been repeatedly confirmed by discoveries of additional functional amyloids. With dozens already known, and with the vigorous rate of discovery, the biology of amyloids is robustly represented by non-pathogenic amyloids.

Download Full-text

Potential regulatory mechanisms of lncRNA in diabetes and its complications

Biochemistry and Cell Biology ◽

10.1139/bcb-2016-0110 ◽

2017 ◽

Vol 95 (3) ◽

pp. 361-367 ◽

Cited By ~ 25

Author(s):

Shui-Dong Feng ◽

Ji-Hua Yang ◽

Chao Hua Yao ◽

Si-Si Yang ◽

Ze-Mei Zhu ◽

...

Keyword(s):

Neurodegenerative Diseases ◽

Regulatory Mechanisms ◽

Protein Coding ◽

Cellular Processes ◽

Biological Relevance ◽

Recent Advances ◽

Non Coding Rnas ◽

Coding Potential

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides without protein-coding potential. Although these molecules were initially considered as “junk products” of transcription without biological relevance, recent advances in research have shown that lncRNA plays an important role, not only in cellular processes such as proliferation, differentiation, and metabolism, but also in the pathological processes of cancers, diabetes, and neurodegenerative diseases. In this review, we focus on the potential regulatory roles of lncRNA in diabetes and the complications associated with diabetes.

Download Full-text

Generation and Activation of Multiple Dimeric Transcription Factors within the NF-κB Signaling System

Molecular and Cellular Biology ◽

10.1128/mcb.01469-07 ◽

2008 ◽

Vol 28 (10) ◽

pp. 3139-3150 ◽

Cited By ~ 91

Author(s):

Soumen Basak ◽

Vincent Feng-Sheng Shih ◽

Alexander Hoffmann

Keyword(s):

Transcription Factors ◽

Steady State ◽

Regulatory Mechanism ◽

Regulatory Mechanisms ◽

Signaling System ◽

Dimer Formation ◽

Wiring Diagram ◽

Cellular Processes ◽

Developmental Signaling ◽

Multiple Cross

ABSTRACT The NF-κB signaling pathway regulates the activity of multiple dimeric transcription factors that are generated from five distinct monomers. The availabilities of specific dimers are regulated during cell differentiation and organ development and determine the cell's responsiveness to inflammatory or developmental signals. An altered dimer distribution is a hallmark of many chronic diseases. Here, we reveal that the cellular processes that generate different NF-κB dimers are highly connected through multiple cross-regulatory mechanisms. First, we find that steady-state expression of RelB is regulated by the canonical pathway and constitutive RelA activity. Indeed, synthesis control of RelB is the major determinant of noncanonical NF-κB dimer activation. Second, processing, not synthesis, of p100 and p105 is mechanistically linked via competitive dimerization with a limited pool of RelA and RelB. This homeostatic cross-regulatory mechanism determines the availability of the p50- and p52-containing dimers and also of the noncanonical IκB p100. Our results inform a wiring diagram to delineate NF-κB dimer formation that emphasizes that inflammatory and developmental signaling cannot be considered separately but are highly interconnected.

Download Full-text

Tuning the proteasome to brighten the end of the journey

AJP Cell Physiology ◽

10.1152/ajpcell.00198.2016 ◽

2016 ◽

Vol 311 (5) ◽

pp. C793-C804 ◽

Cited By ~ 13

Author(s):

Thibault Mayor ◽

Michal Sharon ◽

Michael H. Glickman

Keyword(s):

Cell Cycle Progression ◽

Ubiquitin Proteasome System ◽

Proteasome Activity ◽

Cellular Proteins ◽

Regulatory Mechanisms ◽

Protein Homeostasis ◽

Cycle Progression ◽

Cellular Processes ◽

Age Related ◽

Ubiquitin Proteasome

Degradation by the proteasome is the fate for a large portion of cellular proteins, and it plays a major role in maintaining protein homeostasis, as well as in regulating many cellular processes like cell cycle progression. A decrease in proteasome activity has been linked to aging and several age-related neurodegenerative pathologies and highlights the importance of the ubiquitin proteasome system regulation. While the proteasome has been traditionally viewed as a constitutive element of proteolysis, major studies have highlighted how different regulatory mechanisms can impact its activity. Importantly, alterations of proteasomal activity may have major impacts for its function and in therapeutics. On one hand, increasing proteasome activity could be beneficial to prevent the age-related downfall of protein homeostasis, whereas inhibiting or reducing its activity can prevent the proliferation of cancer cells.

Download Full-text

Targeting polyamine metabolism for cancer therapy and prevention

Biochemical Journal ◽

10.1042/bcj20160383 ◽

2016 ◽

Vol 473 (19) ◽

pp. 2937-2953 ◽

Cited By ~ 70

Author(s):

Tracy R. Murray-Stewart ◽

Patrick M. Woster ◽

Robert A. Casero

Keyword(s):

Cancer Therapy ◽

Drug Targets ◽

Regulatory Mechanisms ◽

Polyamine Metabolism ◽

Neoplastic Disease ◽

Potential Utility ◽

Cellular Processes ◽

Rational Drug ◽

And Function ◽

Positively Charged

The chemically simple, biologically complex eukaryotic polyamines, spermidine and spermine, are positively charged alkylamines involved in many crucial cellular processes. Along with their diamine precursor putrescine, their normally high intracellular concentrations require fine attenuation by multiple regulatory mechanisms to keep these essential molecules within strict physiologic ranges. Since the metabolism of and requirement for polyamines are frequently dysregulated in neoplastic disease, the metabolic pathway and functions of polyamines provide rational drug targets; however, these targets have been difficult to exploit for chemotherapy. It is the goal of this article to review the latest findings in the field that demonstrate the potential utility of targeting the metabolism and function of polyamines as strategies for both chemotherapy and, possibly more importantly, chemoprevention.

Download Full-text

STATISTICAL MECHANICS MODELS FOR X-CHROMOSOME INACTIVATION

Advances in Complex Systems ◽

10.1142/s0219525910002566 ◽

2010 ◽

Vol 13 (03) ◽

pp. 367-376

Author(s):

ANTONIO SCIALDONE ◽

MARIO NICODEMI

Keyword(s):

Statistical Mechanics ◽

X Chromosome ◽

Molecular Mechanisms ◽

X Chromosome Inactivation ◽

Chromosome Inactivation ◽

Regulatory Mechanisms ◽

Random Choice ◽

X Chromosomes ◽

Cellular Processes ◽

Regulatory Processes

We present statistical mechanics models to understand the physical and molecular mechanisms of X-Chromosome Inactivation (XCI), the process whereby a female mammal cell inactivates one of its two X-chromosomes. During XCI, X-chromosomes undergo a series of complex regulatory processes. At the beginning of XCI, the X's recognize and pair, then only one X which is randomly chosen is inactivated. Afterwards, the two X's move to different positions in the cell nucleus according to their different status (active/silenced). Our models illustrate about the still mysterious physical bases underlying all these regulatory steps, i.e., X-chromosome pairing, random choice of inactive X, and "shuttling" of the X's to their post-XCI locations. Our models are based on general and robust thermodynamic roots, and their validity can go beyond XCI, to explain analogous regulatory mechanisms in a variety of cellular processes.

Download Full-text