scholarly journals Centrobin

2005 ◽  
Vol 171 (3) ◽  
pp. 437-445 ◽  
Author(s):  
Chaozhong Zou ◽  
Jun Li ◽  
Yujie Bai ◽  
William T. Gunning ◽  
David E. Wazer ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
S Phase ◽  
Cycle Progression ◽  
Centriole Duplication ◽  
Pericentriolar Material ◽  
Core Components ◽  
Interfering Rna ◽  
Daughter Centriole

In mammalian cells, the centrosome consists of a pair of centrioles and amorphous pericentriolar material. The pair of centrioles, which are the core components of the centrosome, duplicate once per cell cycle. Centrosomes play a pivotal role in orchestrating the formation of the bipolar spindle during mitosis. Recent studies have linked centrosomal activity on centrioles or centriole-associated structures to cytokinesis and cell cycle progression through G1 into the S phase. In this study, we have identified centrobin as a centriole-associated protein that asymmetrically localizes to the daughter centriole. The silencing of centrobin expression by small interfering RNA inhibited centriole duplication and resulted in centrosomes with one or no centriole, demonstrating that centrobin is required for centriole duplication. Furthermore, inhibition of centriole duplication by centrobin depletion led to impaired cytokinesis.

scholarly journals NPAT Expression Is Regulated by E2F and Is Essential for Cell Cycle Progression

2003 ◽  
Vol 23 (8) ◽  
pp. 2821-2833 ◽  
Author(s):  
Guang Gao ◽  
Adrian P. Bracken ◽  
Karina Burkard ◽  
Diego Pasini ◽  
Marie Classon ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
S Phase ◽  
Histone Gene ◽  
Cycle Progression ◽  
Histone Gene Transcription ◽  
E2f Proteins ◽  
Phase Entry

ABSTRACT NPAT is an in vivo substrate of cyclin E-Cdk2 kinase and is thought to play a critical role in coordinated transcriptional activation of histone genes during the G1/S-phase transition and in S-phase entry in mammalian cells. Here we show that NPAT transcription is up-regulated at the G1/S-phase boundary in growth-stimulated cells and that the NPAT promoter responds to activation by E2F proteins. We demonstrate that endogenous E2F proteins interact with the promoter of the NPAT gene in vivo and that induced expression of E2F1 stimulates NPAT mRNA expression, supporting the idea that the expression of NPAT is regulated by E2F. Consistently, we find that the E2F sites in the NPAT promoter are required for its activation during the G1/S-phase transition. Moreover, we show that the expression of NPAT accelerates S-phase entry in cells released from quiescence. The inhibition of NPAT expression by small interfering RNA duplexes impedes cell cycle progression and histone gene expression in tissue culture cells. Thus, NPAT is an important E2F target that is required for cell cycle progression in mammalian cells. As NPAT is involved in the regulation of S-phase-specific histone gene transcription, our findings indicate that NPAT links E2F to the activation of S-phase-specific histone gene transcription.

scholarly journals NEK7 is required for G1 progression and procentriole formation

2017 ◽  
Vol 28 (15) ◽  
pp. 2123-2134 ◽  
Author(s):  
Akshari Gupta ◽  
Yuki Tsuchiya ◽  
Midori Ohta ◽  
Gen Shiratsuchi ◽  
Daiju Kitagawa
Keyword(s):  
Cell Cycle ◽  
Ubiquitin Ligase ◽  
Cell Cycle Progression ◽  
Primary Cilia ◽  
S Phase ◽  
Cycle Progression ◽  
Restriction Point ◽  
Centriole Duplication ◽  
Abnormal Accumulation ◽  
Phase Entry

The decision to commit to the cell cycle is made during G1 through the concerted action of various cyclin–CDK complexes. Not only DNA replication, but also centriole duplication is initiated as cells enter the S-phase. The NIMA-related kinase NEK7 is one of many factors required for proper centriole duplication, as well as for timely cell cycle progression. However, its specific roles in these events are poorly understood. In this study, we find that depletion of NEK7 inhibits progression through the G1 phase in human U2OS cells via down-regulation of various cyclins and CDKs and also inhibits the earliest stages of procentriole formation. Depletion of NEK7 also induces formation of primary cilia in human RPE1 cells, suggesting that NEK7 acts at least before the restriction point during G1. G1-arrested cells in the absence of NEK7 exhibit abnormal accumulation of the APC/C cofactor Cdh1 at the vicinity of centrioles. Furthermore, the ubiquitin ligase APC/CCdh1continuously degrades the centriolar protein STIL in these cells, thus inhibiting centriole assembly. Collectively our results demonstrate that NEK7 is involved in the timely regulation of G1 progression, S-phase entry, and procentriole formation.

scholarly journals The de novo centriole assembly pathway in HeLa cells

2005 ◽  
Vol 168 (5) ◽  
pp. 713-722 ◽  
Author(s):  
Sabrina La Terra ◽  
Christopher N. English ◽  
Polla Hergert ◽  
Bruce F. McEwen ◽  
Greenfield Sluder ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Hela Cells ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
De Novo ◽  
Variable Number ◽  
S Phase ◽  
Cycle Progression ◽  
Assembly Pathway ◽  
Centriole Assembly

It has been reported that nontransformed mammalian cells become arrested during G1 in the absence of centrioles (Hinchcliffe, E., F. Miller, M. Cham, A. Khodjakov, and G. Sluder. 2001. Science. 291:1547–1550). Here, we show that removal of resident centrioles (by laser ablation or needle microsurgery) does not impede cell cycle progression in HeLa cells. HeLa cells born without centrosomes, later, assemble a variable number of centrioles de novo. Centriole assembly begins with the formation of small centrin aggregates that appear during the S phase. These, initially amorphous “precentrioles” become morphologically recognizable centrioles before mitosis. De novo–assembled centrioles mature (i.e., gain abilities to organize microtubules and replicate) in the next cell cycle. This maturation is not simply a time-dependent phenomenon, because de novo–formed centrioles do not mature if they are assembled in S phase–arrested cells. By selectively ablating only one centriole at a time, we find that the presence of a single centriole inhibits the assembly of additional centrioles, indicating that centrioles have an activity that suppresses the de novo pathway.

scholarly journals A UV-responsive G2 checkpoint in rodent cells.

1995 ◽  
Vol 15 (7) ◽  
pp. 3722-3730 ◽  
Author(s):  
D K Orren ◽  
L N Petersen ◽  
V A Bohr
Keyword(s):  
Cell Cycle ◽  
Uv Irradiation ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
Chinese Hamster Ovary Cells ◽  
S Phase ◽  
Serum Starvation ◽  
Cycle Progression ◽  
Synchronized Cells ◽  
G2 Phase

We have studied the effect of UV irradiation on the cell cycle progression of synchronized Chinese hamster ovary cells. Synchronization of cells in S or G2 phase was accomplished by the development of a novel protocol using mimosine, which blocks cell cycle progression at the G1/S boundary. After removal of mimosine, cells proceed synchronously through the S and G2 phases, allowing manipulation of cells at specific points in either phase. Synchronization of cells in G1 was achieved by release of cells after a period of serum starvation. Cells synchronized by these methods were UV irradiated at defined points in G1, S, and G2, and their subsequent progression through the cell cycle was monitored. UV irradiation of G1-synchronized cells caused a dose-dependent delay in entry into S phase. Irradiation of S-phase-synchronized cells inhibited progression through S phase and then resulted in accumulation of cells for a prolonged interval in G2. Apoptosis of a subpopulation of cells during this extended period was noted. UV irradiation of G2-synchronized cells caused a shorter G2 arrest. The arrest itself and its duration were dependent upon the timing (within G2 phase) of the irradiation and the UV dose, respectively. We have thus defined a previously undescribed (in mammalian cells) UV-responsive checkpoint in G2 phase. The implications of these findings with respect to DNA metabolism are discussed.

scholarly journals Cell cycle progression and de novo centriole assembly after centrosomal removal in untransformed human cells

2007 ◽  
Vol 176 (2) ◽  
pp. 173-182 ◽  
Author(s):  
Yumi Uetake ◽  
Jadranka Lončarek ◽  
Joshua J. Nordberg ◽  
Christopher N. English ◽  
Sabrina La Terra ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
De Novo ◽  
S Phase ◽  
Human Cells ◽  
G1 Arrest ◽  
Cycle Progression ◽  
Normal Human ◽  
Centrosomal Proteins

How centrosome removal or perturbations of centrosomal proteins leads to G1 arrest in untransformed mammalian cells has been a mystery. We use microsurgery and laser ablation to remove the centrosome from two types of normal human cells. First, we find that the cells assemble centrioles de novo after centrosome removal; thus, this phenomenon is not restricted to transformed cells. Second, normal cells can progress through G1 in its entirety without centrioles. Therefore, the centrosome is not a necessary, integral part of the mechanisms that drive the cell cycle through G1 into S phase. Third, we provide evidence that centrosome loss is, functionally, a stress that can act additively with other stresses to arrest cells in G1 in a p38-dependent fashion.

scholarly journals The Meiosis-Specific Crs1 Cyclin Is Required for Efficient S-Phase Progression and Stable Nuclear Architecture

2021 ◽  
Vol 22 (11) ◽  
pp. 5483
Author(s):  
Luisa F. Bustamante-Jaramillo ◽  
Celia Ramos ◽  
Cristina Martín-Castellanos
Keyword(s):  
Cell Cycle ◽  
Translational Control ◽  
Cell Cycle Progression ◽  
Nuclear Architecture ◽  
Strand Break ◽  
Spindle Pole ◽  
S Phase ◽  
Cycle Progression ◽  
Single Wave ◽  
Phase Progression

Cyclins and CDKs (Cyclin Dependent Kinases) are key players in the biology of eukaryotic cells, representing hubs for the orchestration of physiological conditions with cell cycle progression. Furthermore, as in the case of meiosis, cyclins and CDKs have acquired novel functions unrelated to this primal role in driving the division cycle. Meiosis is a specialized developmental program that ensures proper propagation of the genetic information to the next generation by the production of gametes with accurate chromosome content, and meiosis-specific cyclins are widespread in evolution. We have explored the diversification of CDK functions studying the meiosis-specific Crs1 cyclin in fission yeast. In addition to the reported role in DSB (Double Strand Break) formation, this cyclin is required for meiotic S-phase progression, a canonical role, and to maintain the architecture of the meiotic chromosomes. Crs1 localizes at the SPB (Spindle Pole Body) and is required to stabilize the cluster of telomeres at this location (bouquet configuration), as well as for normal SPB motion. In addition, Crs1 exhibits CDK(Cdc2)-dependent kinase activity in a biphasic manner during meiosis, in contrast to a single wave of protein expression, suggesting a post-translational control of its activity. Thus, Crs1 displays multiple functions, acting both in cell cycle progression and in several key meiosis-specific events.

scholarly journals Spirulina Crude Protein Promotes the Migration and Proliferation in IEC-6 Cells by Activating EGFR/MAPK Signaling Pathway

Marine Drugs ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 205
Author(s):  
Su-Jin Jeong ◽  
Jeong-Wook Choi ◽  
Min-Kyeong Lee ◽  
Youn-Hee Choi ◽  
Taek-Jeong Nam
Keyword(s):  
Cell Cycle ◽  
Epithelial Cells ◽  
Signaling Pathway ◽  
Crude Protein ◽  
Cell Cycle Progression ◽  
Intestinal Epithelial Cells ◽  
Mapk Signaling ◽  
S Phase ◽  
Intestinal Epithelial ◽  
Cycle Progression

Spirulina is a type of filamentous blue-green microalgae known to be rich in nutrients and to have pharmacological effects, but the effect of spirulina on the small intestine epithelium is not well understood. Therefore, this study aims to investigate the proliferative effects of spirulina crude protein (SPCP) on a rat intestinal epithelial cells IEC-6 to elucidate the mechanisms underlying its effect. First, the results of wound-healing and cell viability assays demonstrated that SPCP promoted migration and proliferation in a dose-dependent manner. Subsequently, when the mechanisms of migration and proliferation promotion by SPCP were confirmed, we found that the epidermal growth factor receptor (EGFR) and mitogen-activated protein (MAPK) signaling pathways were activated by phosphorylation. Cell cycle progression from G0/G1 to S phase was also promoted by SPCP through upregulation of the expression levels of cyclins and cyclin-dependent kinases (Cdks), which regulate cell cycle progression to the S phase. Meanwhile, the expression of cyclin-dependent kinase inhibitors (CKIs), such as p21 and p27, decreased with SPCP. In conclusion, our results indicate that activation of EGFR and its downstream signaling pathway by SPCP treatment regulates cell cycle progression. Therefore, these results contribute to the research on the molecular mechanism for SPCP promoting the migration and proliferation of rat intestinal epithelial cells.

Overexpression of kin17 protein disrupts nuclear morphology and inhibits the growth of mammalian cells

1999 ◽  
Vol 112 (19) ◽  
pp. 3215-3224 ◽  
Author(s):  
P. Kannouche ◽  
J.F. Angulo
Keyword(s):  
Dna Replication ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
Reca Protein ◽  
S Phase ◽  
Expression Vectors ◽  
Nuclear Morphology ◽  
Functional Domain ◽  
Genetic Response ◽  
Cycle Progression

UVC or ionizing radiation of mammalian cells elicits a complex genetic response that allows recovery and cell survival. Kin17 gene, which is highly conserved among mammals, is upregulated during this response. Kin17 gene encodes a 45 kDa protein which binds to DNA and presents a limited similarity with a functional domain of the bacterial RecA protein. Kin17 protein is accumulated in the nucleus of proliferating fibroblasts and forms intranuclear foci. Using expression vectors, we show that overexpression of kin17 protein inhibits cell-cycle progression into S phase. Our results indicate that growth inhibition correlates with disruption of the nuclear morphology which seems to modify the intranuclear network required during the early steps of DNA replication. We report that a mutant encoding a protein deleted from the central domain of kin17 protein enhanced these effects whereas the deletion of the C-terminal domain considerably reduced them. These mutants will be used to elucidate the molecular mechanism by which kin17 protein alters cell growth and DNA replication.

scholarly journals Cubic Membranes Formation in Synchronized Human Hepatocellular Carcinoma Cells Reveals a Possible Role as a Structural Antioxidant Defense System in Cell Cycle Progression

2020 ◽  
Vol 8 ◽  
Author(s):  
Deqin Kong ◽  
Rui Liu ◽  
Jiangzheng Liu ◽  
Qingbiao Zhou ◽  
Jiaxin Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Cell Cycle Progression ◽  
S Phase ◽  
Carcinoma Cells ◽  
Human Hepatocellular Carcinoma ◽  
Cycle Progression ◽  
Hepatocellular Carcinoma Cells ◽  
G2 Phase ◽  
Human Hepatocellular Carcinoma Cells

Cubic membranes (CMs) represent unique biological membrane structures with highly curved three-dimensional periodic minimal surfaces, which have been observed in a wide range of cell types and organelles under various stress conditions (e. g., starvation, virus-infection, and oxidation). However, there are few reports on the biological roles of CMs, especially their roles in cell cycle. Hence, we established a stable cell population of human hepatocellular carcinoma cells (HepG2) of 100% S phase by thymidine treatment, and determined certain parameters in G2 phase released from S phase. Then we found a close relationship between CMs formation and cell cycle, and an increase in reactive oxygen species (ROS) and mitochondrial function. After the synchronization of HepG2 cells were induced, CMs were observed through transmission electron microscope in G2 phase but not in G1, S and M phase. Moreover, the increased ATP production, mitochondrial and intracellular ROS levels were also present in G2 phase, which demonstrated a positive correlation with CMs formation by Pearson correlation analysis. This study suggests that CMs may act as an antioxidant structure in response to mitochondria-derived ROS during G2 phase and thus participate in cell cycle progression.

scholarly journals Effects of Guanine Nucleotide Depletion on Cell Cycle Progression in Human T Lymphocytes

Blood ◽  
1998 ◽  
Vol 91 (8) ◽  
pp. 2896-2904 ◽  
Author(s):  
Josée Laliberté ◽  
Ann Yee ◽  
Yue Xiong ◽  
Beverly S. Mitchell
Keyword(s):  
Cell Cycle ◽  
T Cells ◽  
T Lymphocytes ◽  
Cell Cycle Progression ◽  
S Phase ◽  
Guanine Nucleotides ◽  
Erythroid Cell ◽  
Guanine Nucleotide ◽  
Cycle Progression ◽  
Human T Lymphocytes

Depletion of guanine nucleotide pools after inhibition of inosine monophosphate dehydrogenase (IMPDH) potently inhibits DNA synthesis by arresting cells in G1 and has been shown to induce the differentiation of cultured myeloid and erythroid cell lines, as well as chronic granulocytic leukemic cells after blast transformation. Inhibitors of IMPDH are also highly effective as immunosuppressive agents. The mechanism underlying these pleiotropic effects of depletion of guanine nucleotides is unknown. We have examined the effects of mycophenolic acid (MPA), a potent IMPDH inhibitor, on the cell cycle progression of activated normal human T lymphocytes. MPA treatment resulted in the inhibition of pRb phosphorylation and cell entry into S phase. The expression of cyclin D3, a major component of the cyclin-dependent kinase (CDK) activity required for pRb phosphorylation, was completely abrogated by MPA treatment of T cells activated by interleukin-2 (IL-2) and leucoagglutinin (PHA-L), whereas the expression of cyclin D2, CDK6, and CDK4 was more mildly attenuated. The direct kinase activity of a complex immunoprecipitated with anti-CDK6 antibody was also inhibited. In addition, MPA prevented the IL-2–induced elimination of p27Kip1, a CDK inhibitor, and resulted in the retention of high levels of p27Kip1 in IL-2/PHA-L–treated T cells bound to CDK2. These results indicate that inhibition of the de novo synthesis of guanine nucleotides blocks the transition of normal peripheral blood T lymphocytes from G0 to S phase in early- to mid-G1 and that this cell cycle arrest results from inhibition of the induction of cyclin D/CDK6 kinase and the elimination of p27Kip1 inhibitory activity.

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