Emerging Mechanisms of G 1 /S Cell Cycle Control by Human and Mouse Cytomegaloviruses

The cell division cycle of the early sea urchin embryo is basic. Nonetheless, it has control points in common with the yeast and mammalian cell cycles, at START, mitosis ENTRY and mitosis EXIT. Progression through each control point in sea urchins is triggered by transient increases in intracellular free calcium. The Cai transients control cell cycle progression by translational and post-translational regulation of the cell cycle control proteins pp34 and cyclin. The START Cai transient leads to phosphorylation of pp34 and cyclin synthesis. The mitosis ENTRY Cai transient triggers cyclin phosphorylation. The motosis EXIT transient causes destruction of phosphorylated cyclin. We compare cell cycle regulation by calcium in sea urchin embryos to cell cycle regulation in other eggs and oocytes and in mammalian cells.

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Ubiquitin signaling in cell cycle control and tumorigenesis

Cell Death and Differentiation ◽

10.1038/s41418-020-00648-0 ◽

2020 ◽

Author(s):

Fabin Dang ◽

Li Nie ◽

Wenyi Wei

Keyword(s):

Cell Cycle ◽

Cell Cycle Regulation ◽

Cell Cycle Progression ◽

Kinase Inhibitors ◽

Cell Cycle Control ◽

Ubiquitin Ligases ◽

E3 Ubiquitin Ligases ◽

Cycle Progression ◽

Precise Control ◽

Cycle Regulation

Abstract Cell cycle progression is a tightly regulated process by which DNA replicates and cell reproduces. The major driving force underlying cell cycle progression is the sequential activation of cyclin-dependent kinases (CDKs), which is achieved in part by the ubiquitin-mediated proteolysis of their cyclin partners and kinase inhibitors (CKIs). In eukaryotic cells, two families of E3 ubiquitin ligases, anaphase-promoting complex/cyclosome and Skp1-Cul1-F-box protein complex, are responsible for ubiquitination and proteasomal degradation of many of these CDK regulators, ensuring cell cycle progresses in a timely and precisely regulated manner. In the past couple of decades, accumulating evidence have demonstrated that the dysregulated cell cycle transition caused by inefficient proteolytic control leads to uncontrolled cell proliferation and finally results in tumorigenesis. Based upon this notion, targeting the E3 ubiquitin ligases involved in cell cycle regulation is expected to provide novel therapeutic strategies for cancer treatment. Thus, a better understanding of the diversity and complexity of ubiquitin signaling in cell cycle regulation will shed new light on the precise control of the cell cycle progression and guide anticancer drug development.

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Three independent forms of regulation affect expression of HO, CLN1 and CLN2 during the cell cycle of Saccharomyces cerevisiae.

Genetics ◽

10.1093/genetics/138.4.1015 ◽

1994 ◽

Vol 138 (4) ◽

pp. 1015-1024 ◽

Cited By ~ 5

Author(s):

L Breeden ◽

G Mikesell

Keyword(s):

Saccharomyces Cerevisiae ◽

Cell Cycle ◽

Normal Cell ◽

Cell Cycle Regulation ◽

Cell Cycle Control ◽

G1 Cyclins ◽

Affect Expression ◽

Cdc28 Kinase ◽

Cycle Regulation ◽

Normal Cell Cycle

Abstract The G1 cyclins (CLNs) bind to and activate the CDC28 kinase during the G1 to S transition in Saccharomyces cerevisiae. Two G1 cyclins are regulated at the RNA level so that their RNAs peak at the G1/S boundary. In this report we show that the cell cycle regulation of CLN1 and CLN2 is partially determined by the restricted expression of SW14, a known trans-activator of SCB elements. When SWI4 is constitutively expressed or deleted, cell cycle regulation of CLN1/2 is reduced but not eliminated. In the absence of SwI6, another known regulator of both SCB and MCB elements, cell cycle regulation of the CLNs is also reduced, and the Start-dependence of HO transcription is eliminated. This indicates that SwI6 also plays an important role in the normal cell cycle regulation of all three promoters. When both SwI6 activity and the transcriptional regulation of SW14 are eliminated, cell cycle regulation is further reduced, indicating that these are two independent pathways of regulation. However, a twofold fluctuation in transcript levels still persists under these conditions. This reveals a third source of cell cycle control, which could affect SwI4 activity post-transcriptionally, or reflect the existence of another unidentified regulator of these promoters.

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The Involvement of Two cdc2-related Kinases (CRKs) inTrypanosoma bruceiCell Cycle Regulation and the Distinctive Stage-specific Phenotypes Caused by CRK3 Depletion

Journal of Biological Chemistry ◽

10.1074/jbc.m312862200 ◽

2004 ◽

Vol 279 (19) ◽

pp. 20519-20528 ◽

Cited By ~ 88

Author(s):

Xiaoming Tu ◽

Ching C. Wang

Keyword(s):

Cell Cycle ◽

Cell Cycle Regulation ◽

Cell Cycle Progression ◽

Cell Cycle Control ◽

Eukaryotic Cell ◽

Small Population ◽

Bloodstream Form ◽

Phenotypic Change ◽

Procyclic Form ◽

Cycle Regulation

Cyclin-dependent protein kinases are among the key regulators of eukaryotic cell cycle progression. Potential functions of the five cdc2-related kinases (CRK) inTrypanosoma bruceiwere analyzed using the RNA interference (RNAi) technique. In both the procyclic and bloodstream forms ofT. brucei, CRK1 is apparently involved in controlling the G1/S transition, whereas CRK3 plays an important role in catalyzing cells across the G2/M junction. A knockdown of CRK1 caused accumulation of cells in the G1phase without apparent phenotypic change, whereas depletion of CRK3 enriched cells of both forms in the G2/M phase. However, two distinctive phenotypes were observed between the CRK3-deficient procyclic and bloodstream forms. The procyclic form has a majority of the cells containing a single enlarged nucleus plus one kinetoplast. There is also an enhanced population of anucleated cells, each containing a single kinetoplast known as the zoids (0N1K). The CRK3-depleted bloodstream form has an increased number of one nucleus-two kinetoplast cells (1N2K) and a small population containing aggregated multiple nuclei and multiple kinetoplasts. Apparently, these two forms have different mechanisms in cell cycle regulation. Although the procyclic form can be driven into cytokinesis and cell division by kinetoplast segregation without a completed mitosis, the bloodstream form cannot enter cytokinesis under the same condition. Instead, it keeps going through another G1phase and enters a new S phase resulting in an aggregate of multiple nuclei and multiple kinetoplasts in an undivided cell. The different leakiness in cell cycle regulation between two stage-specific forms of an organism provides an interesting and useful model for further understanding the evolution of cell cycle control among the eukaryotes.

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

eLife ◽

10.7554/elife.52459 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 3

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.

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The Hippo Signaling Pathway in Cancer: A Cell Cycle Perspective

Cancers ◽

10.3390/cancers13246214 ◽

2021 ◽

Vol 13 (24) ◽

pp. 6214

Author(s):

Yi Xiao ◽

Jixin Dong

Keyword(s):

Cell Cycle ◽

Cell Cycle Regulation ◽

Cell Cycle Progression ◽

Cell Cycle Control ◽

Hippo Pathway ◽

Hippo Signaling ◽

Functional Conservation ◽

The Core ◽

The Hippo Pathway ◽

Cycle Regulation

Cell cycle progression is an elaborate process that requires stringent control for normal cellular function. Defects in cell cycle control, however, contribute to genomic instability and have become a characteristic phenomenon in cancers. Over the years, advancement in the understanding of disrupted cell cycle regulation in tumors has led to the development of powerful anti-cancer drugs. Therefore, an in-depth exploration of cell cycle dysregulation in cancers could provide therapeutic avenues for cancer treatment. The Hippo pathway is an evolutionarily conserved regulator network that controls organ size, and its dysregulation is implicated in various types of cancers. Although the role of the Hippo pathway in oncogenesis has been widely investigated, its role in cell cycle regulation has not been comprehensively scrutinized. Here, we specifically focus on delineating the involvement of the Hippo pathway in cell cycle regulation. To that end, we first compare the structural as well as functional conservation of the core Hippo pathway in yeasts, flies, and mammals. Then, we detail the multi-faceted aspects in which the core components of the mammalian Hippo pathway and their regulators affect the cell cycle, particularly with regard to the regulation of E2F activity, the G1 tetraploidy checkpoint, DNA synthesis, DNA damage checkpoint, centrosome dynamics, and mitosis. Finally, we briefly discuss how a collective understanding of cell cycle regulation and the Hippo pathway could be weaponized in combating cancer.

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Inhibition of TFII-I-Dependent Cell Cycle Regulation by p53

Molecular and Cellular Biology ◽

10.1128/mcb.25.24.10940-10952.2005 ◽

2005 ◽

Vol 25 (24) ◽

pp. 10940-10952 ◽

Cited By ~ 24

Author(s):

Zana P. Desgranges ◽

Jinwoo Ahn ◽

Maria B. Lazebnik ◽

Todd Ashworth ◽

Caleb Lee ◽

...

Keyword(s):

Cell Cycle ◽

Cyclin D1 ◽

Cell Cycle Arrest ◽

Cell Cycle Regulation ◽

Cellular Proliferation ◽

Cell Cycle Control ◽

Genotoxic Stress ◽

Dependent Manner ◽

Cycle Arrest ◽

Cycle Regulation

ABSTRACT The multifunctional transcription factor TFII-I is tyrosine phosphorylated in response to extracellular growth signals and transcriptionally activates growth-promoting genes. However, whether activation of TFII-I also directly affects the cell cycle profile is unknown. Here we show that under normal growth conditions, TFII-I is recruited to the cyclin D1 promoter and transcriptionally activates this gene. Most strikingly, upon cell cycle arrest resulting from genotoxic stress and p53 activation, TFII-I is ubiquitinated and targeted for proteasomal degradation in a p53- and ATM (ataxia telangiectasia mutated)-dependent manner. Consistent with a direct role of TFII-I in cell cycle regulation and cellular proliferation, stable and ectopic expression of wild-type TFII-I increases cyclin D1 levels, resulting in accelerated entry to and exit from S phase, and overcomes p53-mediated cell cycle arrest, despite radiation. We further show that the transcriptional regulation of cyclin D1 and cell cycle control by TFII-I are dependent on its tyrosine phosphorylation at positions 248 and 611, sites required for its growth signal-mediated transcriptional activity. Taken together, our data define TFII-I as a growth signal-dependent transcriptional activator that is critical for cell cycle control and proliferation and further reveal that genotoxic stress-induced degradation of TFII-I results in cell cycle arrest.

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