Editorial: Bacterial Transcription Factors and the Cell Cycle

: Selected transcription factors have critical roles to play in organism survival by regulating the expression of genes that control the adaptations needed to handle stress conditions. The retinoblastoma (Rb) protein coupled with the E2F transcription factor family was demonstrated to have roles in controlling the cell cycle during freezing and associated environmental stresses (anoxia, dehydration). Rb phosphorylation or acetylation at different sites provide a mechanism for repressing cell proliferation that is under the control of E2F transcription factors in animals facing stresses that disrupt cellular energetics or cell volume controls. Other central regulators of the cell cycle including Cyclins, Cyclin dependent kinases (Cdks), and checkpoint proteins detect DNA damage or any improper replication, blocking further progression of cell cycle and interrupting cell proliferation. This review provides an insight into the molecular regulatory mechanisms of cell cycle control, focusing on Rb-E2F along with Cyclin-Cdk complexes typically involved in development and differentiation that need to be regulated in order to survive extreme cellular stress.

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Role of n-kb transcription factors, cell-cycle regulators and apoptotic genes in proliferation of MCF-7 cells

International Journal of Pharma and Bio Sciences ◽

10.22376/ijpbs.2017.8.2.b553-561 ◽

2017 ◽

Vol 8 (2) ◽

Author(s):

SHUBHA M. HEGDE ◽

NAVEEN KUMAR M ◽

K. MANJU NATH ◽

S. CHIDANANDA SHARMA

Keyword(s):

Cell Cycle ◽

Transcription Factors ◽

Cell Cycle Regulators ◽

Apoptotic Genes ◽

Mcf 7

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RAE-1 ligands for the NKG2D receptor are regulated by E2F transcription factors, which control cell cycle entry

Journal of Experimental Medicine ◽

10.1084/jem.20120565 ◽

2012 ◽

Vol 209 (13) ◽

pp. 2409-2422 ◽

Cited By ~ 77

Author(s):

Heiyoun Jung ◽

Benjamin Hsiung ◽

Kathleen Pestal ◽

Emily Procyk ◽

David H. Raulet

Keyword(s):

Cell Cycle ◽

Transcription Factors ◽

Stress Responses ◽

Transcriptional Activation ◽

Posttranscriptional Regulation ◽

Cellular Proliferation ◽

Control Cell ◽

T Cell Subsets ◽

Cell Cycle Entry

The NKG2D stimulatory receptor expressed by natural killer cells and T cell subsets recognizes cell surface ligands that are induced on transformed and infected cells and facilitate immune rejection of tumor cells. We demonstrate that expression of retinoic acid early inducible gene 1 (RAE-1) family NKG2D ligands in cancer cell lines and proliferating normal cells is coupled directly to cell cycle regulation. Raet1 genes are directly transcriptionally activated by E2F family transcription factors, which play a central role in regulating cell cycle entry. Induction of RAE-1 occurred in primary cell cultures, embryonic brain cells in vivo, and cells in healing skin wounds and, accordingly, wound healing was delayed in mice lacking NKG2D. Transcriptional activation by E2Fs is likely coordinated with posttranscriptional regulation by other stress responses. These findings suggest that cellular proliferation, as occurs in cancer cells but also other pathological conditions, is a key signal tied to immune reactions mediated by NKG2D-bearing lymphocytes.

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Anti-glioma Efficacy and Mechanism of Action of Tripolinolate A from Tripolium pannonicum

Planta Medica ◽

10.1055/s-0044-101038 ◽

2018 ◽

Vol 84 (11) ◽

pp. 786-794

Author(s):

Weiyun Chai ◽

Lu Chen ◽

Xiao-Yuan Lian ◽

Zhizhen Zhang

Keyword(s):

Cell Cycle ◽

Transcription Factors ◽

Glioma Cells ◽

Inhibitory Effect ◽

Cell Cycle Regulators ◽

Expression Levels ◽

Multiple Tumor ◽

Glioma Growth

AbstractTripolinolate A as a new bioactive phenolic ester was previously isolated from a halophyte of Tripolium pannonicum. However, the in vitro and in vivo anti-glioma effects and mechanism of tripolinolate A have not been investigated. This study has demonstrated that (1) tripolinolate A inhibited the proliferation of different glioma cells with IC50 values of 7.97 to 14.02 µM and had a significant inhibitory effect on the glioma growth in U87MG xenograft nude mice, (2) tripolinolate A induced apoptosis in glioma cells by downregulating the expressions of antiapoptotic proteins and arrested glioma cell cycle at the G2/M phase by reducing the expression levels of cell cycle regulators, and (3) tripolinolate A also remarkably reduced the expression levels of several glioma metabolic enzymes and transcription factors. All data together suggested that tripolinolate A had significant in vitro and in vivo anti-glioma effects and the regulation of multiple tumor-related regulators and transcription factors might be responsible for the activities of tripolinolate A against glioma.

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Cell-Cycle Control of Developmentally Regulated Transcription Factors Accounts for Heterogeneity in Human Pluripotent Cells

Stem Cell Reports ◽

10.1016/j.stemcr.2013.10.009 ◽

2013 ◽

Vol 1 (6) ◽

pp. 532-544 ◽

Cited By ~ 94

Author(s):

Amar M. Singh ◽

James Chappell ◽

Robert Trost ◽

Li Lin ◽

Tao Wang ◽

...

Keyword(s):

Cell Cycle ◽

Transcription Factors ◽

Cell Cycle Control ◽

Pluripotent Cells ◽

Developmentally Regulated

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Bacterial transcription factors involved in global regulation

Molecular Microbiology ◽

10.1046/j.1365-2958.1999.01445.x ◽

1999 ◽

Vol 33 (1) ◽

pp. 8-17 ◽

Cited By ~ 43

Author(s):

Miguel Vicente ◽

Keith F. Chater ◽

Victor de Lorenzo

Keyword(s):

Transcription Factors ◽

Global Regulation ◽

Bacterial Transcription

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Integrating naive Bayes models and external knowledge to examine copper and iron homeostasis in S. cerevisiae

Physiological Genomics ◽

10.1152/physiolgenomics.2000.4.2.127 ◽

2000 ◽

Vol 4 (2) ◽

pp. 127-135 ◽

Cited By ~ 24

Author(s):

E. J. Moler ◽

D. C. Radisky ◽

I. S. Mian

Keyword(s):

Cell Cycle ◽

Transcription Factors ◽

Metal Ion ◽

Iron Homeostasis ◽

Graphical Model ◽

Naive Bayes ◽

Naïve Bayes ◽

Diauxic Shift ◽

Ion Regulation ◽

External Knowledge

A novel suite of analytical techniques and visualization tools are applied to 78 published transcription profiling experiments monitoring 5,687 Saccharomyces cerevisiae genes in studies examining cell cycle, responses to stress, and diauxic shift. A naive Bayes model discovered and characterized 45 classes of gene profile vectors. An enrichment measure quantified the association between these classes and specific external knowledge defined by four sets of categories to which genes can be assigned: 106 protein functions, 5 stages of the cell cycle, 265 transcription factors, and 16 chromosomal locations. Many of the 38 genes in class 42 are known to play roles in copper and iron homeostasis. The 17 uncharacterized open reading frames in this class may be involved in similar homeostatic processes; human homologs of two of them could be associated with as yet undefined disease states arising from aberrant metal ion regulation. The Met4, Met31, and Met32 transcription factors may play a role in coregulating genes involved in copper and iron metabolism. Extensions of the simple graphical model used for clustering to learning more complex models of genetic networks are discussed.

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The transcription factors TFE3 and TFEB amplify p53 dependent transcriptional programs in response to DNA damage

eLife ◽

10.7554/elife.40856 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 15

Author(s):

Eutteum Jeong ◽

Owen A Brady ◽

José A Martina ◽

Mehdi Pirooznia ◽

Ilker Tunc ◽

...

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Transcription Factors ◽

P53 Protein ◽

Cell Cycle Control ◽

Cell Cycle Checkpoints ◽

Dependent Manner ◽

Double Knockout ◽

Protein Levels ◽

Regulation Of Cell Cycle

The transcription factors TFE3 and TFEB cooperate to regulate autophagy induction and lysosome biogenesis in response to starvation. Here we demonstrate that DNA damage activates TFE3 and TFEB in a p53 and mTORC1 dependent manner. RNA-Seq analysis of TFEB/TFE3 double-knockout cells exposed to etoposide reveals a profound dysregulation of the DNA damage response, including upstream regulators and downstream p53 targets. TFE3 and TFEB contribute to sustain p53-dependent response by stabilizing p53 protein levels. In TFEB/TFE3 DKOs, p53 half-life is significantly decreased due to elevated Mdm2 levels. Transcriptional profiles of genes involved in lysosome membrane permeabilization and cell death pathways are dysregulated in TFEB/TFE3-depleted cells. Consequently, prolonged DNA damage results in impaired LMP and apoptosis induction. Finally, expression of multiple genes implicated in cell cycle control is altered in TFEB/TFE3 DKOs, revealing a previously unrecognized role of TFEB and TFE3 in the regulation of cell cycle checkpoints in response to stress.

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An Algorithm for Cellular Reprogramming

10.1101/162974 ◽

2017 ◽

Cited By ~ 1

Author(s):

Scott Ronquist ◽

Geoff Patterson ◽

Markus Brown ◽

Stephen Lindsly ◽

Haiming Chen ◽

...

Keyword(s):

Cell Cycle ◽

Transcription Factor ◽

Transcription Factors ◽

Cell Biology ◽

Human Fibroblasts ◽

Cell Types ◽

Approximate Model ◽

Cellular Reprogramming ◽

Biological Processes ◽

Moderate Complexity

AbstractThe day we understand the time evolution of subcellular elements at a level of detail comparable to physical systems governed by Newton’s laws of motion seems far away. Even so, quantitative approaches to cellular dynamics add to our understanding of cell biology, providing data-guided frameworks that allow us to develop better predictions about, and methods for, control over specific biological processes and system-wide cell behavior. In this paper, we describe an approach to optimizing the use of transcription factors (TFs) in the context of cellular reprogramming. We construct an approximate model for the natural evolution of a cell cycle synchronized population of human fibroblasts, based on data obtained by sampling the expression of 22,083 genes at several time points along the cell cycle. In order to arrive at a model of moderate complexity, we cluster gene expression based on the division of the genome into topologically associating domains (TADs) and then model the dynamics of the TAD expression levels. Based on this dynamical model and known bioinformatics, such as transcription factor binding sites (TFBS) and functions, we develop a methodology for identifying the top transcription factor candidates for a specific cellular reprogramming task. The approach used is based on a device commonly used in optimal control. Our data-guided methodology identifies a number of transcription factors previously validated for reprogramming and/or natural differentiation. Our findings highlight the immense potential of dynamical models, mathematics, and data-guided methodologies for improving strategies for control over biological processes.Significance StatementReprogramming the human genome toward any desirable state is within reach; application of select transcription factors drives cell types toward different lineages in many settings. We introduce the concept of data-guided control in building a universal algorithm for directly reprogramming any human cell type into any other type. Our algorithm is based on time series genome transcription and architecture data and known regulatory activities of transcription factors, with natural dimension reduction using genome architectural features. Our algorithm predicts known reprogramming factors, top candidates for new settings, and ideal timing for application of transcription factors. This framework can be used to develop strategies for tissue regeneration, cancer cell reprogramming, and control of dynamical systems beyond cell biology.

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