scholarly journals S‐phase duration is the main target of cell cycle regulation in neural progenitors of developing ferret neocortex

2015 ◽  
Vol 524 (3) ◽  
pp. 456-470 ◽  
Author(s):  
Miguel Turrero García ◽  
YoonJeung Chang ◽  
Yoko Arai ◽  
Wieland B. Huttner
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
S Phase ◽  
Neural Progenitors ◽  
Phase Duration ◽  
Main Target ◽  
Cycle Regulation

scholarly journals WEE1 kinase inhibitor AZD1775 induces CDK1 kinase-dependent origin firing in unperturbed G1- and S-phase cells

2019 ◽  
Vol 116 (48) ◽  
pp. 23891-23893 ◽  
Author(s):  
Tatiana N. Moiseeva ◽  
Chenao Qian ◽  
Norie Sugitani ◽  
Hatice U. Osmanbeyoglu ◽  
Christopher J. Bakkenist
Keyword(s):  
Cell Cycle ◽  
Clinical Trials ◽  
Cell Cycle Regulation ◽  
Kinase Inhibitor ◽  
S Phase ◽  
Origin Firing ◽  
Replicative Helicase ◽  
Origin Licensing ◽  
Wee1 Kinase ◽  
Cycle Regulation

WEE1 kinase is a key regulator of the G2/M transition. The WEE1 kinase inhibitor AZD1775 (WEE1i) induces origin firing in replicating cells. We show that WEE1i induces CDK1-dependent RIF1 phosphorylation and CDK2- and CDC7-dependent activation of the replicative helicase. WEE1 suppresses CDK1 and CDK2 kinase activities to regulate the G1/S transition after the origin licensing is complete. We identify a role for WEE1 in cell cycle regulation and important effects of AZD1775, which is in clinical trials.

scholarly journals APC/C and retinoblastoma interaction: cross-talk of retinoblastoma protein with the ubiquitin proteasome pathway

2016 ◽  
Vol 36 (5) ◽  
Author(s):  
Ajeena Ramanujan ◽  
Swati Tiwari
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
Alternative Pathway ◽  
Retinoblastoma Protein ◽  
S Phase ◽  
Anaphase Promoting Complex ◽  
Anti Cancer ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Cycle Regulation

The ubiquitin (Ub) ligase anaphase promoting complex/cyclosome (APC/C) and the tumour suppressor retinoblastoma protein (pRB) play key roles in cell cycle regulation. APC/C is a critical regulator of mitosis and G1-phase of the cell cycle whereas pRB keeps a check on proliferation by inhibiting transition to the S-phase. APC/C and pRB interact with each other via the co-activator of APC/C, FZR1, providing an alternative pathway of regulation of G1 to S transition by pRB using a post-translational mechanism. Both pRB and FZR1 have complex roles and are implicated not only in regulation of cell proliferation but also in differentiation, quiescence, apoptosis, maintenance of chromosomal integrity and metabolism. Both are also targeted by transforming viruses. We discuss recent advances in our understanding of the involvement of APC/C and pRB in cell cycle based decisions and how these insights will be useful for development of anti-cancer and anti-viral drugs.

Meiosis-specific cell cycle regulation in maturing Xenopus oocytes

1994 ◽  
Vol 107 (11) ◽  
pp. 3005-3013 ◽  
Author(s):  
K. Ohsumi ◽  
W. Sawada ◽  
T. Kishimoto
Keyword(s):  
Cell Cycle ◽  
Meiotic Division ◽  
Cell Cycle Regulation ◽  
Xenopus Oocytes ◽  
Kinase Activity ◽  
S Phase ◽  
Cell Cycles ◽  
Minute Interval ◽  
Cycle Regulation ◽  
Meiosis I

Meiotic cell cycles differ from mitotic cell cycles in that the former lack S-phase in the interphase between meiosis I and meiosis II. To obtain clues for mechanisms involved in the cell cycle regulation unique to meiosis, we have examined changes in chromosomal morphology and H1 kinase activity during a meiotic period from metaphase I (MI) to metaphase II (MII) in Xenopus oocytes. Using populations of oocytes that underwent germinal vesicle breakdown (GVBD) within a 10 minute interval, we found that the kinase activity declined gradually during the 60 minute period after GVBD and then increased steadily during the following 80 minute interval, showing remarkable differences from the rapid drop and biphasic increase of the kinase activity in intermitotic periods (Solomon et al. (1990) Cell 63, 1013–1024; Dasso and Newport (1990) Cell 61, 811–823). We also found that the exit from MI lagged, by more than 30 minutes, behind the time of lowest H1 kinase activity, whereas the two events took place concomitantly at the end of meiosis II and mitosis. Consequently, the H1 kinase activity was already increasing during the first meiotic division. When H1 kinase activation at MII was delayed by a transient inhibition of protein synthesis after GVBD, oocytes were able to support formation of interphase nuclei and DNA replication between the first meiotic division and the MII arrest, indicating that the cell cycle entered S-phase between meiosis I and meiosis II. These results strongly suggest that the machinery required for entering S-phase has been established in maturing oocytes by the end of meiosis I.(ABSTRACT TRUNCATED AT 250 WORDS)

The Cyclin Interactor p26INCA1 Regulates the Hematopoietic Stem Cell Pool Via CDK Inhibition.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 637-637
Author(s):  
Nicole Baeumer ◽  
Sven Diederichs ◽  
Steffen Koschmieder ◽  
Boris V. Skryabin ◽  
Feng Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bone Marrow ◽  
Stem Cell ◽  
Cell Cycle Regulation ◽  
Kinase Activity ◽  
Bone Marrow Cells ◽  
S Phase ◽  
Hematopoietic Stem ◽  
Cdk2 Activity ◽  
Cycle Regulation

Abstract Cell cycle progression is driven by the kinase activity of cyclin/CDK complexes. Dysregulation of the cell cycle leads to altered cell growth and contributes to tumorigenesis. Recently, we identified p26INCA1 as novel interaction partner of Cyclin A1/CDK2. Here, we characterize the phenotype of Inca1-null mice to uncover the cellular and molecular function of Inca1. Inca1-knockout mice were viable and fertile. FACS analyses revealed that aging mutant animals harbored an increased hematopoietic stem cell (HSC) pool. Bone marrow cells of young mice exhibited enhanced clonogenic replating efficiency in colony formation assays as compared to wildtype mice. Weekly administration of the myeloablative agent 5-fluorouracil (5-FU) led to a significantly shorter life span of Inca1−/ − mice compared to wildtype littermates. The increased 5-FU toxicity might thus be related to a higher number of cycling HSC in Inca1−/ − bone marrow. Analysis of the impact of Inca1 on cell cycle regulation demonstrated that the fraction of Inca1−/ − embryonic fibroblasts (MEFs) in S phase was significantly increased. Ectopic INCA1 expression reduced proliferation and colony formation of proliferating cells such as primary bone marrow cells, HeLa, HuTu80 and 32D cell lines. Serum starvation rapidly induced and mitogenic signals inhibited Inca1 expression providing a further link to cell cycle regulation. To identify the molecular mechanism of cell cycle regulation by Inca1, we investigated the influence of Inca1 on the direct inhibition of CDK2. In spleen lysates from Inca1-deficient mice, cellular CDK2 kinase activity towards Histone H1 was significantly induced compared to lysates of wildtype littermates. In in vitro kinase assays, recombinant INCA1 strongly inhibited CDK2 activity. In addition, we hypothesized that other cyclin kinase inhibitors (CKI) could partially compensate in vivo for the loss of Inca1 function. p21cip1/waf1 mRNA and protein expression were induced in Inca1−/ − MEFs compared to wildtype cells hinting at a partial compensation of the loss of Inca1 by induction of p21. Loss of Inca1 combined with p21 knockdown synergistically increased S-phase. These results indicate that Inca1 could be functionally related to p21 and that the rather mild phenotype observed in Inca1−/ − mice and the modest differences in Cdk activity observed in cell lysates lacking Inca1 could be due to compensatory induction of the CKI p21. In summary, loss of Inca1 increased cell proliferation, replating efficiency, S-phase progression, and Cdk2 activity whereas gain of Inca1 suppressed these cell functions. Inca1 expression was induced during cell cycle arrest. We conclude that Inca1 could be a novel cell cycle suppressor regulating the quiescence of HSCs through the inhibition of Cdk2.

scholarly journals A Sequence Element Downstream of the Yeast HTB1 Gene Contributes to mRNA 3′ Processing and Cell Cycle Regulation

2002 ◽  
Vol 22 (24) ◽  
pp. 8415-8425 ◽  
Author(s):  
Susan G. Campbell ◽  
Marcel li del Olmo ◽  
Paul Beglan ◽  
Ursula Bond
Keyword(s):  
Cell Cycle ◽  
Site Selection ◽  
Cleavage Site ◽  
Cell Cycle Regulation ◽  
Binding Activity ◽  
S Phase ◽  
Sequence Element ◽  
Reading Frame ◽  
Protein Factor ◽  
Cycle Regulation

ABSTRACT Histone mRNAs accumulate in the S phase and are rapidly degraded as cells progress into the G2 phase of the cell cycle. In Saccharomyces cerevisiae, fusion of the 3′ untranslated region and downstream sequences of the yeast histone gene HTB1 to a neomycin phosphotransferase open reading frame is sufficient to confer cell cycle regulation on the resulting chimera gene (neo-HTB1). We have identified a sequence element, designated the distal downstream element (DDE), that influences both the 3′-end cleavage site selection and the cell cycle regulation of the neo-HTB1 mRNA. Mutations in the DDE, which is located approximately 110 nucleotides downstream of the HTB1 gene, lead to a delay in the accumulation of the neo-HTB1 mRNA in the S phase and a lack of mRNA turnover in the G2 phase. The DDE is transcribed as part of the primary transcript and binds a protein factor(s). Maximum binding is observed in the S phase of the cell cycle, and mutations that affect the turnover of the HTB1 mRNA alter the binding activity. While located in the same general region, mutations that affect 3′-end cleavage site selection act independently from those that alter the cell cycle regulation.

scholarly journals Intrinsic Negative Cell Cycle Regulation Provided by PIP Box- and Cul4Cdt2-Mediated Destruction of E2f1 during S Phase

2008 ◽  
Vol 15 (6) ◽  
pp. 890-900 ◽  
Author(s):  
Shusaku T. Shibutani ◽  
Aida Flor A. de la Cruz ◽  
Vuong Tran ◽  
William J. Turbyfill ◽  
Tânia Reis ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
S Phase ◽  
Negative Cell ◽  
Cycle Regulation

scholarly journals An advanced cell cycle tag toolbox reveals principles underlying temporal control of structure-selective nucleases

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Julia Bittmann ◽  
Rokas Grigaitis ◽  
Lorenzo Galanti ◽  
Silas Amarell ◽  
Florian Wilfling ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Regulation ◽  
Cell Cycle Control ◽  
S Phase ◽  
Specific Cell ◽  
Protein Functionality ◽  
M Phase ◽  
Cell Cycle Phases ◽  
Cycle Regulation

Cell cycle tags allow to restrict target protein expression to specific cell cycle phases. Here, we present an advanced toolbox of cell cycle tag constructs in budding yeast with defined and compatible peak expression that allow comparison of protein functionality at different cell cycle phases. We apply this technology to the question of how and when Mus81-Mms4 and Yen1 nucleases act on DNA replication or recombination structures. Restriction of Mus81-Mms4 to M phase but not S phase allows a wildtype response to various forms of replication perturbation and DNA damage in S phase, suggesting it acts as a post-replicative resolvase. Moreover, we use cell cycle tags to reinstall cell cycle control to a deregulated version of Yen1, showing that its premature activation interferes with the response to perturbed replication. Curbing resolvase activity and establishing a hierarchy of resolution mechanisms are therefore the principal reasons underlying resolvase cell cycle regulation.

scholarly journals tmRNA in Caulobacter crescentus Is Cell Cycle Regulated by Temporally Controlled Transcription and RNA Degradation

2003 ◽  
Vol 185 (6) ◽  
pp. 1825-1830 ◽  
Author(s):  
Kenneth C. Keiler ◽  
Lucy Shapiro
Keyword(s):  
Cell Cycle ◽  
Small Rna ◽  
Half Life ◽  
Cell Cycle Regulation ◽  
Caulobacter Crescentus ◽  
Rna Degradation ◽  
S Phase ◽  
Replication Initiation ◽  
Dna Replication Initiation ◽  
Cycle Regulation

ABSTRACT SsrA, or tmRNA, is a small RNA found in all bacteria that intervenes in selected translation reactions to target the nascent polypeptide for rapid proteolysis. We have found that the abundance of SsrA RNA in Caulobacter crescentus is regulated with respect to the cell cycle. SsrA RNA abundance increases in late G1 phase, peaks during the G1-S transition, and declines in early S phase, in keeping with the reported role for SsrA in the timing of DNA replication initiation. Cell cycle regulation of SsrA RNA is accomplished by a combination of temporally controlled transcription and regulated RNA degradation. Transcription from the ssrA promoter peaks late in G1, just before the peak in SsrA RNA abundance. SsrA RNA is stable in G1-phase cells and late S-phase cells but is degraded with a half-life of 4 to 5 min at the onset of S phase. This degradation is surprising, since SsrA RNA is both highly structured and highly abundant. This is the first observation of a structural RNA that is cell cycle regulated.

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