scholarly journals TheSac3Homologueshd1Is Involved in Mitotic Progression in Mammalian Cells

2004 ◽  
Vol 279 (44) ◽  
pp. 46182-46190 ◽  
Author(s):  
Sefat-e- Khuda ◽  
Mikoto Yoshida ◽  
Yan Xing ◽  
Tatsuya Shimasaki ◽  
Motohiro Takeya ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
Spindle Assembly Checkpoint ◽  
Fluorescent Protein ◽  
Spindle Assembly ◽  
Centrosome Duplication ◽  
Cycle Progression ◽  
M Phase ◽  
Green Fluorescent

SaccharomycesSac3 required for actin assembly was shown to be involved in DNA replication. Here, we studied the function of a mammalian homologue SHD1 in cell cycle progression. SHD1 is localized on centrosomes at interphase and at spindle poles and mitotic spindles, similar to α-tubulin, at M phase. RNA interference suppression of endogenousshd1caused defects in centrosome duplication and spindle formation displaying cells with a single apparent centrosome and down-regulated Mad2 expression, generating increased micronuclei. Conversely, increased expression of SHD1 by DNA transfection withshd1-green fluorescent protein (gfp) vector for a fusion protein of SHD1 and GFP caused abnormalities in centrosome duplication displaying cells with multiple centrosomes and deregulated spindle assembly with up-regulated Mad2 expression until anaphase, generating polyploidy cells. These results demonstrated thatshd1is involved in cell cycle progression, in particular centrosome duplication and a spindle assembly checkpoint function.

scholarly journals Extracellular Signal-regulated Kinase 1/2 Activity Is Not Required in Mammalian Cells during Late G2 for Timely Entry into or Exit from Mitosis

2006 ◽  
Vol 17 (12) ◽  
pp. 5227-5240 ◽  
Author(s):  
Mio Shinohara ◽  
Alexei V. Mikhailov ◽  
Julio A. Aguirre-Ghiso ◽  
Conly L. Rieder
Keyword(s):  
Cell Cycle ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Live Cells ◽  
Cycle Progression ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Sustained Inhibition

Extracellular signal-regulated kinase (ERK)1/2 activity is reported to be required in mammalian cells for timely entry into and exit from mitosis (i.e., the G2-mitosis [G2/M] and metaphase-anaphase [M/A] transitions). However, it is unclear whether this involvement reflects a direct requirement for ERK1/2 activity during these transitions or for activating gene transcription programs at earlier stages of the cell cycle. To examine these possibilities, we followed live cells in which ERK1/2 activity was inhibited through late G2 and mitosis. We find that acute inhibition of ERK1/2 during late G2 and through mitosis does not affect the timing of the G2/M or M/A transitions in normal or transformed human cells, nor does it impede spindle assembly, inactivate the p38 stress-activated checkpoint during late G2 or the spindle assembly checkpoint during mitosis. Using CENP-F as a marker for progress through G2, we also show that sustained inhibition of ERK1/2 transiently delays the cell cycle in early/mid-G2 via a p53-dependent mechanism. Together, our data reveal that ERK1/2 activity is required in early G2 for a timely entry into mitosis but that it does not directly regulate cell cycle progression from late G2 through mitosis in normal or transformed mammalian cells.

scholarly journals Dominant Alleles of Saccharomyces cerevisiae CDC20 Reveal Its Role in Promoting Anaphase

Genetics ◽  
1998 ◽  
Vol 148 (2) ◽  
pp. 599-610
Author(s):  
Eric J Schott ◽  
M Andrew Hoyt
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Spindle Assembly Checkpoint ◽  
Limiting Factor ◽  
Mutant Form ◽  
Loss Of Function ◽  
Cycle Progression ◽  
Inhibit Cell Cycle Progression ◽  
M Phase

Abstract We identified an allele of Saccharomyces cerevisiae CDC20 that exhibits a spindle-assembly checkpoint defect. Previous studies indicated that loss of CDC20 function caused cell cycle arrest prior to the onset of anaphase. In contrast, CDC20-50 caused inappropriate cell cycle progression through M phase in the absence of mitotic spindle function. This effect of CDC20-50 was dominant over wild type and was eliminated by a second mutation causing loss of function, suggesting that it encodes an overactive form of Cdc20p. Overexpression of CDC20 was found to cause a similar checkpoint defect, causing bypass of the preanaphase arrest produced by either microtubule-depolymerizing compounds or MPS1 overexpression. CDC20 overexpression was also able to overcome the anaphase delay caused by high levels of the anaphase inhibitor Pds1p, but not a mutant form immune to anaphase-promoting complex- (APC-)mediated proteolysis. CDC20 overexpression was unable to promote anaphase in cells deficient in APC function. These findings suggest that Cdc20p is a limiting factor that promotes anaphase entry by antagonizing Pds1p. Cdc20p may promote the APC-dependent proteolytic degradation of Pds1p and other factors that act to inhibit cell cycle progression through mitosis.

scholarly journals Cpc2, a Fission Yeast Homologue of Mammalian RACK1 Protein, Interacts with Ran1 (Pat1) Kinase To Regulate Cell Cycle Progression and Meiotic Development

2000 ◽  
Vol 20 (11) ◽  
pp. 4016-4027 ◽  
Author(s):  
Maureen McLeod ◽  
Boris Shor ◽  
Anthony Caporaso ◽  
Wei Wang ◽  
Hua Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Fission Yeast ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
Fluorescent Protein ◽  
Yeast Cells ◽  
Anchoring Protein ◽  
Signal Transduction Proteins ◽  
Green Fluorescent

ABSTRACT The Schizosaccharomyces pombe ran1/pat1 gene regulates the transition between mitosis and meiosis. Inactivation of Ran1 (Pat1) kinase is necessary and sufficient for cells to exit the cell cycle and undergo meiosis. The yeast two-hybrid interaction trap was used to identify protein partners for Ran1/Pat1. Here we report the identification of one of these, Cpc2. Cpc2 encodes a homologue of RACK1, a WD protein with homology to the β subunit of heterotrimeric G proteins. RACK1 is a highly conserved protein, although its function remains undefined. In mammalian cells, RACK1 physically associates with some signal transduction proteins, including Src and protein kinase C. Fission yeast cells containing a cpc2 null allele are viable but cell cycle delayed. cpc2Δ cells fail to accumulate in G1 when starved of nitrogen. This leads to defects in conjugation and meiosis. Copurification studies show that although Cpc2 and Ran1 (Pat1) physically associate, Cpc2 does not alter Ran1 (Pat1) kinase activity in vitro. Using a Ran1 (Pat1) fusion to green fluorescent protein, we show that localization of the kinase is impaired in cpc2Δ cells. Thus, in parallel with the proposed role of RACK1 in mammalian cells, fission yeast cpc2 may function as an anchoring protein for Ran1 (Pat1) kinase. All defects associated with loss of cpc2 are reversed in cells expressing mammalian RACK1, demonstrating that the fission yeast and mammalian gene products are indeed functional homologues.

scholarly journals The Human Cytomegalovirus IE86 Protein Can Block Cell Cycle Progression after Inducing Transition into the S Phase of Permissive Cells

2000 ◽  
Vol 74 (15) ◽  
pp. 7108-7118 ◽  
Author(s):  
Eain A. Murphy ◽  
Daniel N. Streblow ◽  
Jay A. Nelson ◽  
Mark F. Stinski
Keyword(s):  
Cell Cycle ◽  
Protein Expression ◽  
Human Cytomegalovirus ◽  
Cell Cycle Progression ◽  
Hcmv Infection ◽  
Fluorescent Protein ◽  
Cell Types ◽  
S Phase ◽  
Cycle Progression ◽  
Green Fluorescent

ABSTRACT Human cytomegalovirus (HCMV) infection of permissive cells has been reported to induce a cell cycle halt. One or more viral proteins may be involved in halting progression at different stages of the cell cycle. We investigated how HCMV infection, and specifically IE86 protein expression, affects the cell cycles of permissive and nonpermissive cells. We used a recombinant virus that expresses the green fluorescent protein (GFP) to determine the effects of HCMV on the cell cycle of permissive cells. Fluorescence by GFP allowed us to select for only productively infected cells. Replication-defective adenovirus vectors expressing the IE72 or IE86 protein were also used to efficiently transduce 95% or more of the cells. The adenovirus-expressed IE86 protein was determined to be functional by demonstrating negative autoregulation of the major immediate-early promoter and activation of an early viral promoter in the context of the viral genome. To eliminate adenovirus protein effects, plasmids expressing GFP for fluorescent selection of only transfected cells and wild-type IE86 protein or a mutant IE86 protein were tested in permissive and nonpermissive cells. HCMV infection induced the entry of U373 cells into the S phase. All permissive cells infected with HCMV were blocked in cell cycle progression and could not divide. After either transduction or transfection and IE86 protein expression, the number of all permissive or nonpermissive cell types in the S phase increased significantly, but the cells could no longer divide. The IE72 protein did not have a significant effect on the S phase. Since IE86 protein inhibits cell cycle progression, the IE2 gene in a human fibroblast IE86 protein-expressing cell line was sequenced. The IE86 protein in these retrovirus-transduced cells has mutations in a critical region of the viral protein. The locations of the mutations and the function of the IE86 protein in controlling cell cycle progression are discussed.

The effect of drugs on the cell cycle ofGiardia intestinalis

Parasitology ◽  
1989 ◽  
Vol 99 (3) ◽  
pp. 333-339 ◽  
Author(s):  
G. F. Hoyne ◽  
P. F.L. Boreham ◽  
P. G. Parsons ◽  
C. Ward ◽  
B. Biggs
Keyword(s):  
Cell Cycle ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
Flow Cytometric Analysis ◽  
Protozoan Parasite ◽  
Cycle Progression ◽  
Flow Cytometric ◽  
Mammalian Cell Cycle ◽  
M Phase ◽  
Dna Histograms

SummaryFlow cytometric analysis of the binucleated protozoan parasiteGiardia intestinalisgave DNA histograms with a broad Gl peak and a definable G2 + M peak with twice the DNA content of Gl. Twenty-four hour treatment with metronidazole arrested cell cycle progression of susceptible trophozoites in the G2 + M phase, but had no effect, even at toxic doses, on the DNA histogram of a line selected for resistance to metronidazole. Furazolidone was inhibitory to both stocks, causing an arrest in the S and G2 + M phases. Inhibitors of the mammalian cell cycle were also tested. Hydroxyurea, which blocks mammalian cells in Gl/S, and razoxane, which blocks in G2 + M, arrested trophozoites in the G2 + M phase whereas colchicine and gamma-irradiation had little or no effect on the cell cycle ofG. intestinalis. These results suggest that the cell cycle ofG. intestinalismay be controlled in a different manner from mammalian cells.

scholarly journals Cdk1-Mediated Phosphorylation of Human ATF7 at Thr-51 and Thr-53 Promotes Cell-Cycle Progression into M Phase

PLoS ONE ◽  
2014 ◽  
Vol 9 (12) ◽  
pp. e116048 ◽  
Author(s):  
Hitomi Hasegawa ◽  
Kenichi Ishibashi ◽  
Shoichi Kubota ◽  
Chihiro Yamaguchi ◽  
Ryuzaburo Yuki ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
M Phase

scholarly journals Regulation of Cell Cycle Progression by Growth Factor-Induced Cell Signaling

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3327
Author(s):  
Zhixiang Wang
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Signaling Pathways ◽  
Tyrosine Kinases ◽  
Cell Cycle Progression ◽  
Phase Cell ◽  
Growth Factor Signaling ◽  
Cycle Progression ◽  
M Phase

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.

scholarly journals Akt/Protein Kinase B-Dependent Phosphorylation and Inactivation of WEE1Hu Promote Cell Cycle Progression at G2/M Transition

2005 ◽  
Vol 25 (13) ◽  
pp. 5725-5737 ◽  
Author(s):  
Kazuhiro Katayama ◽  
Naoya Fujita ◽  
Takashi Tsuruo
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Kinase Inhibitor ◽  
Phosphorylation Site ◽  
Cytoplasmic Localization ◽  
M Cell ◽  
Serine Threonine Kinase ◽  
Cycle Progression ◽  
M Phase ◽  
Promote Cell Cycle Progression

ABSTRACT The serine/threonine kinase Akt is known to promote cell growth by regulating the cell cycle in G1 phase through activation of cyclin/Cdk kinases and inactivation of Cdk inhibitors. However, how the G2/M phase is regulated by Akt remains unclear. Here, we show that Akt counteracts the function of WEE1Hu. Inactivation of Akt by chemotherapeutic drugs or the phosphatidylinositide-3-OH kinase inhibitor LY294002 induced G2/M arrest together with the inhibitory phosphorylation of Cdc2. Because the increased Cdc2 phosphorylation was completely suppressed by wee1hu gene silencing, WEE1Hu was associated with G2/M arrest induced by Akt inactivation. Further analyses revealed that Akt directly bound to and phosphorylated WEE1Hu during the S to G2 phase. Serine-642 was identified as an Akt-dependent phosphorylation site. WEE1Hu kinase activity was not affected by serine-642 phosphorylation. We revealed that serine-642 phosphorylation promoted cytoplasmic localization of WEE1Hu. The nuclear-to-cytoplasmic translocation was mediated by phosphorylation-dependent WEE1Hu binding to 14-3-3θ but not 14-3-3β or -σ. These results indicate that Akt promotes G2/M cell cycle progression by inducing phosphorylation-dependent 14-3-3θ binding and cytoplasmic localization of WEE1Hu.

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