A casein kinase I isoform is required for proper cell cycle progression in the fertilized mouse oocyte

1997 ◽  
Vol 110 (24) ◽  
pp. 3083-3090 ◽  
Author(s):  
S.D. Gross ◽  
C. Simerly ◽  
G. Schatten ◽  
R.A. Anderson
Keyword(s):  
Cell Cycle ◽  
Subcellular Localization ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
T Antigen ◽  
Casein Kinase ◽  
Mouse Oocyte ◽  
Casein Kinase I ◽  
Sv40 Large T Antigen ◽  
Cycle Progression

Casein kinase I is a family of serine/threonine protein kinases common to all eukaryotes. In yeast, casein kinase I homologues have been linked to the regulation of growth, DNA repair and cell division. In addition, their subcellular localization to membraneous structures and the nucleus is essential for function. In higher eukaryotes, there exist seven genetically distinct isoforms: (alpha), ss, (gamma)1, (gamma)2, (gamma)3, (delta) and (epsilon). Casein kinase I(alpha) exhibits a cell cycle-dependent subcellular localization including an association with cytosolic vesicular structures and the nucleus during interphase, and the spindle during mitosis. casein kinase I has also been shown to modulate critical regulators of growth and DNA synthesis/repair in mammalian cells such as SV40 large T antigen and p53. These results suggest that casein kinase I may be involved in processes similar to those ascribed to the yeast casein kinase I homologues. To define a role for casein kinase I(alpha) in cell cycle regulation, the mouse oocyte was utilized because of its well-defined cell cycle and ease of micromanipulation. Immunofluorescence studies from meiosis I of maturation to the first zygotic cleavage demonstrated that the kinase was associated with structures similar to those previously reported. Microinjection of casein kinase I(alpha) antibodies at metaphase II-arrest and G2 phase, had no effect on the completion of second meiosis or first division. However, microinjection of these antibodies during the early pronucleate phase prior to S-phase onset blocked uptake of the kinase into pronuclei and interfered with proper and timely cell cycle progression to first cleavage. These results suggest that the kinase regulates the progression from interphase to mitosis during the first cell cycle.

scholarly journals Casein Kinase Iγ2 Impairs Fibroblasts Actin Stress Fibers Formation and Delays Cell Cycle Progression in G1

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Mathieu Latreille ◽  
Afnan Abu-Thuraia ◽  
Rossella Oliva ◽  
Dongmei Zuo ◽  
Louise Larose
Keyword(s):  
Cell Cycle ◽  
Catalytic Activity ◽  
Actin Cytoskeleton ◽  
Cell Cycle Progression ◽  
Casein Kinase ◽  
Stress Fibers ◽  
Casein Kinase I ◽  
Cycle Progression ◽  
Protein Levels ◽  
Actin Stress Fibers

Actin cytoskeleton remodeling is under the regulation of multiple proteins with various activities. Here, we demonstrate that theγ2 isoform of Casein Kinase I (CKIγ2) is part of a novel molecular path regulating the formation of actin stress fibers. We show that overexpression of CKIγ2 in fibroblasts alters cell morphology by impairing actin stress fibers formation. We demonstrate that this is concomitant with increased phosphorylation of the CDK inhibitorp27Kipand lower levels of activated RhoA, and is dependent on CKIγ2 catalytic activity. Moreover, we report that roscovitine, a potent inhibitor of cyclin-dependent kinases, including Cdk5, decreasesp27Kipprotein levels and restores actin stress fibers formation in CKIγ2 overexpressing cells, suggesting the existence of a CKIγ2-Cdk5-p27Kip-RhoA pathway in regulating actin remodeling. On the other hand, we also show that in a manner independent of its catalytic activity, CKIγ2 delays cell cycle progression through G1. Collectively our findings reveal that CKIγ2 is a novel player in the control of actin cytoskeleton dynamics and cell proliferation.

Cyclin specificity: how many wheels do you need on a unicycle?

2001 ◽  
Vol 114 (10) ◽  
pp. 1811-1820 ◽  
Author(s):  
M.E. Miller ◽  
F.R. Cross
Keyword(s):  
Cell Cycle ◽  
Subcellular Localization ◽  
Cell Cycle Progression ◽  
Eukaryotic Cell ◽  
Cyclin Dependent Kinase ◽  
Temporal Expression ◽  
Cycle Progression

Cyclin-dependent kinase (CDK) activity is essential for eukaryotic cell cycle events. Multiple cyclins activate CDKs in all eukaryotes, but it is unclear whether multiple cyclins are really required for cell cycle progression. It has been argued that cyclins may predominantly act as simple enzymatic activators of CDKs; in opposition to this idea, it has been argued that cyclins might target the activated CDK to particular substrates or inhibitors. Such targeting might occur through a combination of factors, including temporal expression, protein associations, and subcellular localization.

scholarly journals CNOT 6L couples the selective degradation of maternal transcripts to meiotic cell cycle progression in mouse oocyte

2018 ◽  
Vol 37 (24) ◽  
Author(s):  
Qian‐Qian Sha ◽  
Jia‐Li Yu ◽  
Jing‐Xin Guo ◽  
Xing‐Xing Dai ◽  
Jun‐Chao Jiang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Mouse Oocyte ◽  
Meiotic Cell ◽  
Cycle Progression ◽  
Selective Degradation ◽  
Maternal Transcripts

scholarly journals Bromodomain Protein Brd4 Binds to GTPase-Activating SPA-1, Modulating Its Activity and Subcellular Localization

2004 ◽  
Vol 24 (20) ◽  
pp. 9059-9069 ◽  
Author(s):  
Andrea Farina ◽  
Masakazu Hattori ◽  
Jun Qin ◽  
Yoshihiro Nakatani ◽  
Nagahiro Minato ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Subcellular Localization ◽  
Cell Cycle Progression ◽  
Ectopic Expression ◽  
Gtpase Activating Protein ◽  
Functional Importance ◽  
Cycle Progression ◽  
Proper Balance ◽  
Mammalian Protein ◽  
Normal Cell Cycle

ABSTRACT Brd4 is a mammalian protein that contains a double bromodomain. It binds to chromatin and regulates cell cycle progression at multiple stages. By immunopurification and mass spectrometry, we identified a Rap GTPase-activating protein (GAP), signal-induced proliferation-associated protein 1 (SPA-1), as a factor that interacts with Brd4. SPA-1 localizes to the cytoplasm and to a lesser degree in the nucleus, while Brd4 resides in the nucleus. Bifluorescence complementation revealed that Brd4 and SPA-1 interact with each other in the nucleus of living cells. Supporting the functional importance of the interaction, Brd4 enhanced Rap GAP activity of SPA-1. Furthermore ectopic expression of SPA-1 and Brd4 redirected subcellular localization of the partner and disrupted normal cell cycle progression. These effects were, however, reversed by coexpression of the two proteins, indicating that a proper balance between Brd4 and SPA-1 in G2 is required for cell division. This work reveals a novel link between Brd4 and a GTPase-dependent mitogenic signaling pathway.

scholarly journals Effects of conditional depletion of topoisomerase II on cell cycle progression in mammalian cells

Cell Cycle ◽  
2011 ◽  
Vol 10 (20) ◽  
pp. 3505-3514 ◽  
Author(s):  
Ruth E. Gonzalez ◽  
Chang-Uk Lim ◽  
Kelly Cole ◽  
Christine Hanko Bianchini ◽  
Gary P. Schools ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
Topoisomerase Ii ◽  
Cycle Progression

scholarly journals Phosphorylation Controls Ikaros's Ability To Negatively Regulate the G1-S Transition

2004 ◽  
Vol 24 (7) ◽  
pp. 2797-2807 ◽  
Author(s):  
Pablo Gómez-del Arco ◽  
Kazushige Maki ◽  
Katia Georgopoulos
Keyword(s):  
Cell Cycle ◽  
Dna Binding ◽  
Cell Cycle Progression ◽  
Rapid Development ◽  
Binding Activity ◽  
Casein Kinase ◽  
Cycle Progression ◽  
Dna Binding Activity ◽  
Increased Activity ◽  
Inactivating Mutations

ABSTRACT Ikaros is a key regulator of lymphocyte proliferative responses. Inactivating mutations in Ikaros cause antigen-mediated lymphocyte hyperproliferation and the rapid development of leukemia and lymphoma. Here we show that Ikaros's ability to negatively regulate the G1-S transition can be modulated by phosphorylation of a serine/threonine-rich conserved region (p1) in exon 8. Ikaros phosphorylation in p1 is induced during the G1-S transition. Mutations that prevent phosphorylation in p1 increase Ikaros's ability to impede cell cycle progression and its affinity for DNA. Casein kinase II, whose increased activity in lymphocytes leads to transformation, is a key player in Ikaros p1 phosphorylation. We thus propose that Ikaros's activity as a regulator of the G1-S transition is controlled by phosphorylation in response to signaling events that downmodulate its DNA binding activity.

scholarly journals Cell cycle progression after cleavage failure

2004 ◽  
Vol 165 (5) ◽  
pp. 609-615 ◽  
Author(s):  
Yumi Uetake ◽  
Greenfield Sluder
Keyword(s):  
Cell Cycle ◽  
Cell Line ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
Human Fibroblasts ◽  
Human Cell Line ◽  
Cycle Progression ◽  
Binucleate Cells ◽  
Normal Human ◽  
Cleavage Failure

Failure of cells to cleave at the end of mitosis is dangerous to the organism because it immediately produces tetraploidy and centrosome amplification, which is thought to produce genetic imbalances. Using normal human and rat cells, we reexamined the basis for the attractive and increasingly accepted proposal that normal mammalian cells have a “tetraploidy checkpoint” that arrests binucleate cells in G1, thereby preventing their propagation. Using 10 μM cytochalasin to block cleavage, we confirm that most binucleate cells arrest in G1. However, when we use lower concentrations of cytochalasin, we find that binucleate cells undergo DNA synthesis and later proceed through mitosis in >80% of the cases for the hTERT-RPE1 human cell line, primary human fibroblasts, and the REF52 cell line. These observations provide a functional demonstration that the tetraploidy checkpoint does not exist in normal mammalian somatic cells.

scholarly journals Cell Cycle Progression in Monkey Cells Expressing Simian Virus 40 Small t Antigen from Adenovirus Vectors

1998 ◽  
Vol 72 (12) ◽  
pp. 9637-9644 ◽  
Author(s):  
Alan K. Howe ◽  
Stéphanie Gaillard ◽  
John S. Bennett ◽  
Kathleen Rundell
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Mapk Pathway ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Dependent Manner ◽  
Cycle Progression ◽  
Adenovirus Vectors ◽  
Small T Antigen

ABSTRACT The simian virus 40 small t antigen (small-t) is required for optimal viral replication and transformation, especially during the infection of nondividing cells, suggesting that the function of small-t is to promote cell cycle progression. The mechanism through which small-t promotes cell growth reflects, in part, its binding and inhibition of protein phosphatase 2A (PP2A). The use of recombinant adenoviruses allows small-t expression in a majority of cells in a population, thus providing a convenient source of cells for biochemical analyses. In monkey kidney CV1 cells, small-t expressed from these adenovirus vectors activated the mitogen-activated protein kinase (MAPK) pathway, induced JNK activity, and increased AP-1 DNA-binding activity, all in a PP2A-dependent manner. Expression of small-t also caused an increase in the phosphorylation of the Na+/H+ antiporter, a mitogen-activated ion exchanger whose activity correlates with its phosphorylation. At least part of the antiporter phosphorylation induced by small-t reflected activation of the MAPK pathway, as suggested by results of assays using a chemical inhibitor of the MAPK-activating kinase, MEK. Finally, small-t expression from adenovirus vectors promoted efficient cell cycle progression by growth-arrested cells. These vectors should facilitate further analysis of effects of small-t on cell cycle mediators.

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