Control of cell cycle transcription during G1 and S phases
01 Aug 2013-Nature Reviews Molecular Cell Biology (Nature Publishing Group)-Vol. 14, Iss: 8, pp 518-528
TL;DR: The complex molecular mechanisms that control the temporal order of transcriptional activation and inactivation, determine distinct functional subgroups of genes and link cell cycle-dependent transcription to DNA replication stress in yeast and mammals are revealed.
Abstract: The accurate transition from G1 phase of the cell cycle to S phase is crucial for the control of eukaryotic cell proliferation, and its misregulation promotes oncogenesis. During G1 phase, growth-dependent cyclin-dependent kinase (CDK) activity promotes DNA replication and initiates G1-to-S phase transition. CDK activation initiates a positive feedback loop that further increases CDK activity, and this commits the cell to division by inducing genome-wide transcriptional changes. G1-S transcripts encode proteins that regulate downstream cell cycle events. Recent work is beginning to reveal the complex molecular mechanisms that control the temporal order of transcriptional activation and inactivation, determine distinct functional subgroups of genes and link cell cycle-dependent transcription to DNA replication stress in yeast and mammals.
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TL;DR: This article describes a computational workflow for low-level analyses of scRNA-seq data, based primarily on software packages from the open-source Bioconductor project, which covers basic steps including quality control, data exploration and normalization, as well as more complex procedures such as cell cycle phase assignment.
Abstract: Single-cell RNA sequencing (scRNA-seq) is widely used to profile the transcriptome of individual cells This provides biological resolution that cannot be matched by bulk RNA sequencing, at the cost of increased technical noise and data complexity The differences between scRNA-seq and bulk RNA-seq data mean that the analysis of the former cannot be performed by recycling bioinformatics pipelines for the latter Rather, dedicated single-cell methods are required at various steps to exploit the cellular resolution while accounting for technical noise This article describes a computational workflow for low-level analyses of scRNA-seq data, based primarily on software packages from the open-source Bioconductor project It covers basic steps including quality control, data exploration and normalization, as well as more complex procedures such as cell cycle phase assignment, identification of highly variable and correlated genes, clustering into subpopulations and marker gene detection Analyses were demonstrated on gene-level count data from several publicly available datasets involving haematopoietic stem cells, brain-derived cells, T-helper cells and mouse embryonic stem cells This will provide a range of usage scenarios from which readers can construct their own analysis pipelines
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Cites background from "Control of cell cycle transcription..."
...This may be due to the conservation of the transcriptional program associated with the cell cycle (Bertoli et al., 2013; Conboy et al., 2007)....
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Journal Article•
738 citations
TL;DR: This review will focus on the multiple functions of p21 in cell cycle regulation, apoptosis and gene transcription after DNA damage and briefly discuss the pathways and factors that have critical roles in p21 expression and activity.
711 citations
Cites background from "Control of cell cycle transcription..."
...It is believed that the regulation of cell growth by p21 is mediated by control of E2F activity [3,4]....
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...P21 s also known to inhibit the kinase activity of cyclin A/CDK1, 2, esulting in cell cycle inhibition through and into S phase [3,25]....
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TL;DR: A review will be primarily focused on STAT3 downstream target genes that have been validated to associate with tumorigenesis and/or malignant biology of human cancers.
Abstract: Since its discovery, the STAT3 transcription factor has been extensively studied for its function as a transcriptional regulator and its role as a mediator of development, normal physiology, and pathology of many diseases, including cancers. These efforts have uncovered an array of genes that can be positively and negatively regulated by STAT3, alone and in cooperation with other transcription factors. Through regulating gene expression, STAT3 has been demonstrated to play a pivotal role in many cellular processes including oncogenesis, tumor growth and progression, and stemness. Interestingly, recent studies suggest that STAT3 may behave as a tumor suppressor by activating expression of genes known to inhibit tumorigenesis. Additional evidence suggested that STAT3 may elicit opposing effects depending on cellular context and tumor types. These mixed results signify the need for a deeper understanding of STAT3, including its upstream regulators, parallel transcription co-regulators, and downstream target genes. To help facilitate fulfilling this unmet need, this review will be primarily focused on STAT3 downstream target genes that have been validated to associate with tumorigenesis and/or malignant biology of human cancers.
398 citations
Cites background from "Control of cell cycle transcription..."
...Thus, induction of cyclin D proteins, including cyclin D1, promotes entry into the S-phase and cell proliferation....
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...In particular, the cyclin D proteins regulate the G1/S-phase transition as the cyclin D proteins (D1, D2, and D3) increase expression leading to interaction with and activation of cyclin dependent kinases 4 and 6 (CDK4/6), which phosphorylates the retinoblastoma (Rb) protein to initiate S-phase [106]....
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TL;DR: The regulation of ERKs, and their control of cell proliferation, cell survival, cell growth, cell metabolism, cell migration and cell differentiation are discussed.
Abstract: The proteins extracellular signal-regulated kinase 1 (ERK1) and ERK2 are the downstream components of a phosphorelay pathway that conveys growth and mitogenic signals largely channelled by the small RAS GTPases By phosphorylating widely diverse substrates, ERK proteins govern a variety of evolutionarily conserved cellular processes in metazoans, the dysregulation of which contributes to the cause of distinct human diseases The mechanisms underlying the regulation of ERK1 and ERK2, their mode of action and their impact on the development and homeostasis of various organisms have been the focus of much attention for nearly three decades In this Review, we discuss the current understanding of this important class of kinases We begin with a brief overview of the structure, regulation, substrate recognition and subcellular localization of ERK1 and ERK2 We then systematically discuss how ERK signalling regulates six fundamental cellular processes in response to extracellular cues These processes are cell proliferation, cell survival, cell growth, cell metabolism, cell migration and cell differentiation
388 citations
References
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TL;DR: A comprehensive catalog of yeast genes whose transcript levels vary periodically within the cell cycle is created, and it is found that the mRNA levels of more than half of these 800 genes respond to one or both of these cyclins.
Abstract: We sought to create a comprehensive catalog of yeast genes whose transcript levels vary periodically within the cell cycle. To this end, we used DNA microarrays and samples from yeast cultures sync...
5,176 citations
TL;DR: The main role of pRB is to act as a signal transducer connecting the cell cycle clock with the transcriptional machinery, allowing the clock to control the expression of banks of genes that mediate advance of the cell through a critical phase of its growth cycle.
4,904 citations
TL;DR: The authors' improving understanding of DNA-damage responses is providing new avenues for disease management, and these responses are biologically significant because they prevent diverse human diseases.
Abstract: The prime objective for every life form is to deliver its genetic material, intact and unchanged, to the next generation. This must be achieved despite constant assaults by endogenous and environmental agents on the DNA. To counter this threat, life has evolved several systems to detect DNA damage, signal its presence and mediate its repair. Such responses, which have an impact on a wide range of cellular events, are biologically significant because they prevent diverse human diseases. Our improving understanding of DNA-damage responses is providing new avenues for disease management.
4,871 citations
TL;DR: Control of p53's transcriptional activity is crucial for determining which p53 response is activated, a decision that must be understood if the next generation of drugs that selectively activate or inhibit p53 are to be exploited efficiently.
2,775 citations
TL;DR: The rapid growth in the size of the E2F literature hides the fact that several fundamental questions have not been fully answered, and the second section of this review details five unresolved issues that have been highlighted by recent publications.
Abstract: Much has been written about the functions of the E2F transcription factor and the product of the retinoblastoma tumor suppressor gene (pRB). These proteins have been described in terms that vary from ‘‘master regulators of cell cycle and differentiation’’ to ‘‘peripheral factors that lie outside the core cell cycle machinery.’’ Most often, pRB and E2F are described in short and simple terms as opposing molecules that control the G1to Sphase transition. There is an element of truth in each of these descriptions. E2Fand pRB-family proteins clearly play important roles in cell proliferation and differentiation. The extent to which they are master regulators or peripheral factors is a question of semantics, and these terms tell us more about the writer than the proteins. Perhaps the most important development in the E2F literature is the appreciation that E2F and pRB are not unique molecules with functions that can be defined in black and white terms. Instead, E2F and pRB represent families of related proteins that have diverse and occasionally contradictory activities. We now know a great deal about E2F complexes and pRB-family proteins and the emerging picture defies a one-line explanation. The fascinating variety of activities ascribed to various E2F complexes challenges us to place these into context and to find the right perspective. This review is presented into two sections. The first section summarizes the tremendous progress into the composition and properties of E2F and the many interactions that coordinately regulate E2F-dependent transcription. The rapid growth in the size of the E2F literature hides the fact that several fundamental questions have not been fully answered. Because of this, the second section of this review details five unresolved issues that have been highlighted by recent publications. It is impossible to cover all of the relevant E2F literature in a single review and readers are referred to reviews by Farnham (1995); Sardet et al. (1997); Helin (1998); and Yamasaki (1998) for a comprehensive survey.
2,357 citations