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Nature Reviews. Molecular Cell Biology Aug 2013The 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... (Review)
Review
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.
Topics: Animals; Cell Cycle; Cell Cycle Proteins; Cyclin-Dependent Kinases; G1 Phase; Humans; Mammals; Models, Biological; S Phase; Transcription, Genetic; Yeasts
PubMed: 23877564
DOI: 10.1038/nrm3629 -
Stem Cell Reviews and Reports Jun 2018MicroRNAs (miRNAs) are a class of small non-coding RNA molecules involved in the regulation of gene expression. They are involved in the fine-tuning of fundamental... (Review)
Review
MicroRNAs (miRNAs) are a class of small non-coding RNA molecules involved in the regulation of gene expression. They are involved in the fine-tuning of fundamental biological processes such as proliferation, differentiation, survival and apoptosis in many cell types. Emerging evidence suggests that miRNAs regulate critical pathways involved in stem cell function. Several miRNAs have been suggested to target transcripts that directly or indirectly coordinate the cell cycle progression of stem cells. Moreover, previous studies have shown that altered expression levels of miRNAs can contribute to pathological conditions, such as cancer, due to the loss of cell cycle regulation. However, the precise mechanism underlying miRNA-mediated regulation of cell cycle in stem cells is still incompletely understood. In this review, we discuss current knowledge of miRNAs regulatory role in cell cycle progression of stem cells. We describe how specific miRNAs may control cell cycle associated molecules and checkpoints in embryonic, somatic and cancer stem cells. We further outline how these miRNAs could be regulated to influence cell cycle progression in stem cells as a potential clinical application.
Topics: Adult Stem Cells; Animals; Cell Cycle; Humans; MicroRNAs; Neoplastic Stem Cells; Stem Cells
PubMed: 29541978
DOI: 10.1007/s12015-018-9808-y -
Cells Aug 2022Cell cycle and cell adhesion are two interdependent cellular processes regulating each other, reciprocally, in every cell cycle phase. The cell adhesion to the... (Review)
Review
Cell cycle and cell adhesion are two interdependent cellular processes regulating each other, reciprocally, in every cell cycle phase. The cell adhesion to the extracellular matrix (ECM) via integrin receptors triggers signaling pathways required for the cell cycle progression; the passage from the G1 to S phase and the completion of cytokinesis are the best-understood events. Growing evidence, however, suggests more adhesion-dependent regulatory aspects of the cell cycle, particularly during G2 to M transition and early mitosis. Conversely, the cell cycle machinery regulates cell adhesion in manners recently shown driven mainly by cyclin-dependent kinase 1 (CDK1). This review summarizes the recent findings regarding the role of integrin-mediated cell adhesion and its downstream signaling components in regulating the cell cycle, emphasizing the cell cycle progression through the G2 and early M phases. Further investigations are required to raise our knowledge about the molecular mechanisms of crosstalk between cell adhesion and the cell cycle in detail.
Topics: Cell Adhesion; Cell Cycle; Cell Cycle Checkpoints; Integrins; Mitosis
PubMed: 36010598
DOI: 10.3390/cells11162521 -
Bulletin Du Cancer Oct 2011Genomic DNA is constantly under stress of endogenous and exogenous DNA damaging agents. Without proper care, the DNA damage causes an alteration of the genomic structure... (Review)
Review
Genomic DNA is constantly under stress of endogenous and exogenous DNA damaging agents. Without proper care, the DNA damage causes an alteration of the genomic structure and can lead to cell death or the occurrence of mutations involved in tumorigenesis. During the process of evolution, organisms have acquired a series of response mechanisms and repair of DNA damage, thereby ensuring the maintenance of genome stability and faithful transmission of genetic information. The checkpoints are the major mechanisms by which a cell can respond to DNA damage, either by actively stopping the cell cycle or by induction of apoptosis. Two parallel signalling pathways, ATM and ATR respond to genotoxic stress by activating their downstream target proteins including the two effectors kinases CHK1 and CHK2. Promising preliminary data render these proteins potential targets for therapeutic development against cancer.
Topics: Aneuploidy; Apoptosis; Ataxia Telangiectasia Mutated Proteins; Cell Cycle; Cell Cycle Proteins; Checkpoint Kinase 1; Checkpoint Kinase 2; DNA Damage; DNA Repair; DNA-Binding Proteins; Enzyme Activation; Genomic Instability; Humans; Interphase; Mitosis; Molecular Targeted Therapy; Neoplasms; Phosphorylation; Protein Kinases; Protein Serine-Threonine Kinases; Signal Transduction; Tumor Suppressor Proteins
PubMed: 21669563
DOI: 10.1684/bdc.2011.1382 -
Methods in Molecular Biology (Clifton,... 2014Cell cycle checkpoints are surveillance mechanisms that monitor the order, integrity, and fidelity of the major events of the cell cycle. These include growth to the...
Cell cycle checkpoints are surveillance mechanisms that monitor the order, integrity, and fidelity of the major events of the cell cycle. These include growth to the appropriate cell size, the replication and integrity of the chromosomes, and their accurate segregation at mitosis. Many of these mechanisms are ancient in origin and highly conserved, and hence have been heavily informed by studies in simple organisms such as the yeasts. Others have evolved in higher organisms, and control alternative cell fates with significant impact on tumor suppression. Here, we consider these different checkpoint pathways and the consequences of their dysfunction on cell fate.
Topics: Cell Cycle; Cell Cycle Checkpoints; Cell Size; DNA Damage; DNA Repair; DNA Replication; Genomic Instability; Humans; Mitosis; Yeasts
PubMed: 24906307
DOI: 10.1007/978-1-4939-0888-2_2 -
Developmental Cell Mar 2004The Keystone Symposium on the Cell Cycle and Development brought together biologists with an interest in how cell cycle control is integrated into the ontogenetic... (Review)
Review
The Keystone Symposium on the Cell Cycle and Development brought together biologists with an interest in how cell cycle control is integrated into the ontogenetic program of multicellular organisms, and showcased research using a wide variety of systems from both animals and plants. A clear indication from the meeting is that this research is changing the conventional wisdom on both cell cycle control and development.
Topics: Animals; Cell Communication; Cell Cycle; Cell Differentiation; Cell Division; DNA Replication; Models, Biological; Morphogenesis; Plants
PubMed: 15030756
DOI: 10.1016/s1534-5807(04)00067-x -
Trends in Cell Biology Oct 2015Pluripotent stem cells (PSCs) retain the ability to differentiate into a wide range of cell types while undergoing self-renewal. They also exhibit an unusual mode of... (Review)
Review
Pluripotent stem cells (PSCs) retain the ability to differentiate into a wide range of cell types while undergoing self-renewal. They also exhibit an unusual mode of cell cycle regulation, reflected by a cell cycle structure where G1 and G2 phases are truncated. When individual PSCs are exposed to specification cues, they activate developmental programs and remodel the cell cycle so that the length of G1 and overall cell division times increase. The response of individual stem cells to pro-differentiation signals is strikingly heterogeneous, resulting in asynchronous differentiation. Recent evidence indicates that this phenomenon is due to cell cycle-dependent mechanisms that restrict the initial activation of developmental genes to the G1 phase. This suggests a broad biological mechanism where multipotent cells are 'primed' to initiate cell fate decisions during their transition through G1. Here, I discuss mechanisms underpinning the commitment towards the differentiated state and its relation to the cell cycle.
Topics: Cell Cycle; Cell Differentiation; Cell Division; G1 Phase; Genetic Heterogeneity; Humans; Pluripotent Stem Cells
PubMed: 26410405
DOI: 10.1016/j.tcb.2015.07.007 -
Cells Nov 2021The cell cycle is the series of events that take place in a cell, which drives it to divide and produce two new daughter cells. The typical cell cycle in eukaryotes is... (Review)
Review
The cell cycle is the series of events that take place in a cell, which drives it to divide and produce two new daughter cells. The typical cell cycle in eukaryotes is composed of the following phases: G1, S, G2, and M phase. Cell cycle progression is mediated by cyclin-dependent kinases (Cdks) and their regulatory cyclin subunits. However, the driving force of cell cycle progression is growth factor-initiated signaling pathways that control the activity of various Cdk-cyclin complexes. While the mechanism underlying the role of growth factor signaling in G1 phase of cell cycle progression has been largely revealed due to early extensive research, little is known regarding the function and mechanism of growth factor signaling in regulating other phases of the cell cycle, including S, G2, and M phase. In this review, we briefly discuss the process of cell cycle progression through various phases, and we focus on the role of signaling pathways activated by growth factors and their receptor (mostly receptor tyrosine kinases) in regulating cell cycle progression through various phases.
Topics: Animals; Cell Cycle; Humans; Intercellular Signaling Peptides and Proteins; Models, Biological; Signal Transduction
PubMed: 34943835
DOI: 10.3390/cells10123327 -
International Journal of Molecular... Jun 2021Cell cycle regulation is orchestrated by a complex network of interactions between proteins, enzymes, cytokines, and cell cycle signaling pathways, and is vital for cell... (Review)
Review
Cell cycle regulation is orchestrated by a complex network of interactions between proteins, enzymes, cytokines, and cell cycle signaling pathways, and is vital for cell proliferation, growth, and repair. The occurrence, development, and metastasis of tumors are closely related to the cell cycle. Cell cycle regulation can be synergistic with chemotherapy in two aspects: inhibition or promotion. The sensitivity of tumor cells to chemotherapeutic drugs can be improved with the cooperation of cell cycle regulation strategies. This review presented the mechanism of the commonly used chemotherapeutic drugs and the effect of the cell cycle on tumorigenesis and development, and the interaction between chemotherapy and cell cycle regulation in cancer treatment was briefly introduced. The current collaborative strategies of chemotherapy and cell cycle regulation are discussed in detail. Finally, we outline the challenges and perspectives about the improvement of combination strategies for cancer therapy.
Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Cycle; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Drug Delivery Systems; Humans
PubMed: 34203270
DOI: 10.3390/ijms22136923 -
Nucleic Acids Research Dec 2020Efficient S phase entry is essential for development, tissue repair, and immune defences. However, hyperactive or expedited S phase entry causes replication stress, DNA... (Review)
Review
Efficient S phase entry is essential for development, tissue repair, and immune defences. However, hyperactive or expedited S phase entry causes replication stress, DNA damage and oncogenesis, highlighting the need for strict regulation. Recent paradigm shifts and conflicting reports demonstrate the requirement for a discussion of the G1/S transition literature. Here, we review the recent studies, and propose a unified model for the S phase entry decision. In this model, competition between mitogen and DNA damage signalling over the course of the mother cell cycle constitutes the predominant control mechanism for S phase entry of daughter cells. Mitogens and DNA damage have distinct sensing periods, giving rise to three Commitment Points for S phase entry (CP1-3). S phase entry is mitogen-independent in the daughter G1 phase, but remains sensitive to DNA damage, such as single strand breaks, the most frequently-occurring lesions that uniquely threaten DNA replication. To control CP1-3, dedicated hubs integrate the antagonistic mitogenic and DNA damage signals, regulating the stoichiometric cyclin: CDK inhibitor ratio for ultrasensitive control of CDK4/6 and CDK2. This unified model for the G1/S cell cycle transition combines the findings of decades of study, and provides an updated foundation for cell cycle research.
Topics: Cell Cycle; Cell Cycle Checkpoints; Cell Division; DNA Damage; DNA Replication; G1 Phase; Humans; S Phase; Signal Transduction
PubMed: 33166394
DOI: 10.1093/nar/gkaa1002