Cyclin C influences the timing of mitosis in fission yeast

The multiprotein Mediator complex is required for the regulated transcription of nearly all RNA polymerase II–dependent genes. Mediator contains the Cdk8 regulatory subcomplex, which directs periodic transcription and influences cell cycle progression in fission yeast. Here we investigate the role of CycC, the cognate cyclin partner of Cdk8, in cell cycle control. Previous reports suggested that CycC interacts with other cellular Cdks, but a fusion of CycC to Cdk8 reported here did not cause any obvious cell cycle phenotypes. We find that Cdk8 and CycC interactions are stabilized within the Mediator complex and the activity of Cdk8-CycC is regulated by other Mediator components. Analysis of a mutant yeast strain reveals that CycC, together with Cdk8, primarily affects M-phase progression but mutations that release Cdk8 from CycC control also affect timing of entry into S phase.

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

Cells ◽

10.3390/cells10123327 ◽

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.

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The Multiple Roles of the Cdc14 Phosphatase in Cell Cycle Control

International Journal of Molecular Sciences ◽

10.3390/ijms21030709 ◽

2020 ◽

Vol 21 (3) ◽

pp. 709

Author(s):

Javier Manzano-López ◽

Fernando Monje-Casas

Keyword(s):

Cell Cycle ◽

Cell Cycle Progression ◽

Current Knowledge ◽

Cell Cycle Control ◽

Multiple Roles ◽

Special Focus ◽

Cyclin Dependent Kinase ◽

Yeast Saccharomyces Cerevisiae ◽

Cycle Progression

The Cdc14 phosphatase is a key regulator of mitosis in the budding yeast Saccharomyces cerevisiae. Cdc14 was initially described as playing an essential role in the control of cell cycle progression by promoting mitotic exit on the basis of its capacity to counteract the activity of the cyclin-dependent kinase Cdc28/Cdk1. A compiling body of evidence, however, has later demonstrated that this phosphatase plays other multiple roles in the regulation of mitosis at different cell cycle stages. Here, we summarize our current knowledge about the pivotal role of Cdc14 in cell cycle control, with a special focus in the most recently uncovered functions of the phosphatase.

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Cell cycle control

Oxford Textbook of Oncology ◽

10.1093/med/9780199656103.003.0004 ◽

2016 ◽

pp. 31-41

Author(s):

Simon M. Carr ◽

Nicholas B. La Thangue

Keyword(s):

Cell Cycle ◽

Final Stage ◽

Cell Cycle Progression ◽

Cell Cycle Control ◽

Control Mechanisms ◽

Chromosomal Dna ◽

Cycle Progression ◽

M Phase ◽

Cellular Components ◽

Regulate Cell Cycle Progression

All cells arise by the division of existing cells in a highly regulated series of events known as the cell cycle. Whilst duplication of other cellular contents occurs throughout all stages of the cycle, chromosomal DNA is replicated only once at a stage known as S phase. Once this is complete, distribution of chromosomes and other cellular components occurs during the final stage of the cell cycle, known as M phase, or mitosis. The cell cycle is therefore regulated in a temporal fashion, so that entry into subsequent cell cycle stages only occurs once the previous stage has been completed. A number of signalling mechanisms monitor the integrity of cell cycle progression, and later cell cycle stages can be delayed if any errors need correction. This chapter gives an overview of the major control mechanisms that regulate cell cycle progression, and how these are circumvented during the onset of cancer.

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Canonical and Alternative Pathways in Cyclin-Dependent Kinase 1/Cyclin B Inactivation upon M-Phase Exit in Xenopus laevis Cell-Free Extracts

Enzyme Research ◽

10.4061/2011/523420 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8

Author(s):

Jacek Z. Kubiak ◽

Mohammed El Dika

Keyword(s):

Cell Cycle ◽

Xenopus Laevis ◽

Cell Cycle Progression ◽

Cyclin B ◽

Cyclin Dependent Kinase ◽

Cycle Progression ◽

Alternative Pathways ◽

Global View ◽

M Phase

Cyclin-Dependent Kinase 1 (CDK1) is the major M-phase kinase known also as the M-phase Promoting Factor or MPF. Studies performed during the last decade have shown many details of how CDK1 is regulated and also how it regulates the cell cycle progression. Xenopus laevis cell-free extracts were widely used to elucidate the details and to obtain a global view of the role of CDK1 in M-phase control. CDK1 inactivation upon M-phase exit is a primordial process leading to the M-phase/interphase transition during the cell cycle. Here we discuss two closely related aspects of CDK1 regulation in Xenopus laevis cell-free extracts: firstly, how CDK1 becomes inactivated and secondly, how other actors, like kinases and phosphatases network and/or specific inhibitors, cooperate with CDK1 inactivation to assure timely exit from the M-phase.

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Emerging concepts of nucleolar assembly

Journal of Cell Science ◽

10.1242/jcs.115.11.2265 ◽

2002 ◽

Vol 115 (11) ◽

pp. 2265-2270 ◽

Cited By ~ 4

Author(s):

Danièle Hernandez-Verdun ◽

Pascal Roussel ◽

Jeannine Gébrane-Younès

Keyword(s):

Cell Cycle ◽

Ribosome Biogenesis ◽

Cell Cycle Progression ◽

Cell Cycle Control ◽

Cycle Progression ◽

Cooperative Interactions ◽

Cellular Processes ◽

Nuclear Domain ◽

New Ideas

The nucleolus is a large nuclear domain and the site of ribosome biogenesis. It is also at the parting of the ways of several cellular processes, including cell cycle progression, gene silencing, and ribonucleoprotein complex formation. Consequently, a functional nucleolus is crucial for cell survival. Recent investigations of nucleolar assembly during the cell cycle and during embryogenesis have provided an integrated view of the dynamics of this process. Moreover, they have generated new ideas about cell cycle control of nucleolar assembly, the dynamics of the delivery of the RNA processing machinery, the formation of prenucleolar bodies, the role of precursor ribosomal RNAs in stabilizing the nucleolar machinery and the fact that nucleolar assembly is completed by cooperative interactions between chromosome territories. This has opened a new area of research into the dynamics of nuclear organization and the integration of nuclear functions.

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Cyclin C: The Story of a Non-Cycling Cyclin

Biology ◽

10.3390/biology8010003 ◽

2019 ◽

Vol 8 (1) ◽

pp. 3 ◽

Cited By ~ 3

Author(s):

Jan Ježek ◽

Daniel G. J. Smethurst ◽

David C. Stieg ◽

Z. A. C. Kiss ◽

Sara E. Hanley ◽

...

Keyword(s):

Cell Cycle ◽

Rna Polymerase Ii ◽

Cell Cycle Progression ◽

Mitochondrial Fission ◽

Yeast Cells ◽

Regulatory Function ◽

Transcriptional Regulatory ◽

Cyclin C ◽

Accessory Subunits

The class I cyclin family is a well-studied group of structurally conserved proteins that interact with their associated cyclin-dependent kinases (Cdks) to regulate different stages of cell cycle progression depending on their oscillating expression levels. However, the role of class II cyclins, which primarily act as transcription factors and whose expression remains constant throughout the cell cycle, is less well understood. As a classic example of a transcriptional cyclin, cyclin C forms a regulatory sub-complex with its partner kinase Cdk8 and two accessory subunits Med12 and Med13 called the Cdk8-dependent kinase module (CKM). The CKM reversibly associates with the multi-subunit transcriptional coactivator complex, the Mediator, to modulate RNA polymerase II-dependent transcription. Apart from its transcriptional regulatory function, recent research has revealed a novel signaling role for cyclin C at the mitochondria. Upon oxidative stress, cyclin C leaves the nucleus and directly activates the guanosine 5’-triphosphatase (GTPase) Drp1, or Dnm1 in yeast, to induce mitochondrial fragmentation. Importantly, cyclin C-induced mitochondrial fission was found to increase sensitivity of both mammalian and yeast cells to apoptosis. Here, we review and discuss the biology of cyclin C, focusing mainly on its transcriptional and non-transcriptional roles in tumor promotion or suppression.

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The S-phase-induced lncRNA SUNO1 promotes cell proliferation by controlling YAP1/Hippo signaling pathway

eLife ◽

10.7554/elife.55102 ◽

2020 ◽

Vol 9 ◽

Author(s):

Qinyu Hao ◽

Xinying Zong ◽

Qinyu Sun ◽

Yo-Chuen Lin ◽

You Jin Song ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Rna Polymerase Ii ◽

Cell Cycle Progression ◽

S Phase ◽

Cancer Prognosis ◽

Cycle Phase ◽

Hippo Signaling ◽

Cycle Progression

Cell cycle is a cellular process that is subject to stringent control. In contrast to the wealth of knowledge of proteins controlling the cell cycle, very little is known about the molecular role of lncRNAs (long noncoding RNAs) in cell-cycle progression. By performing genome-wide transcriptome analyses in cell-cycle-synchronized cells, we observed cell-cycle phase-specific induction of >2000 lncRNAs. Further, we demonstrate that an S-phase-upregulated lncRNA, SUNO1, facilitates cell-cycle progression by promoting YAP1-mediated gene expression. SUNO1 facilitates the cell-cycle-specific transcription of WTIP, a positive regulator of YAP1, by promoting the co-activator, DDX5-mediated stabilization of RNA polymerase II on chromatin. Finally, elevated SUNO1 levels are associated with poor cancer prognosis and tumorigenicity, implying its pro-survival role. Thus, we demonstrate the role of a S-phase up-regulated lncRNA in cell-cycle progression via modulating the expression of genes controlling cell proliferation.

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The Morphogenesis Checkpoint in Saccharomyces cerevisiae: Cell Cycle Control of Swe1p Degradation by Hsl1p and Hsl7p

Molecular and Cellular Biology ◽

10.1128/mcb.19.10.6929 ◽

1999 ◽

Vol 19 (10) ◽

pp. 6929-6939 ◽

Cited By ~ 117

Author(s):

John N. McMillan ◽

Mark S. Longtine ◽

Rey A. L. Sia ◽

Chandra L. Theesfeld ◽

Elaine S. G. Bardes ◽

...

Keyword(s):

Saccharomyces Cerevisiae ◽

Cell Cycle ◽

Cell Cycle Progression ◽

Cell Cycle Control ◽

Negative Regulators ◽

Cycle Progression ◽

Bud Formation ◽

M Phase ◽

Subsequent Degradation ◽

Morphogenesis Checkpoint

ABSTRACT In Saccharomyces cerevisiae, the Wee1 family kinase Swe1p is normally stable during G1 and S phases but is unstable during G2 and M phases due to ubiquitination and subsequent degradation. However, perturbations of the actin cytoskeleton lead to a stabilization and accumulation of Swe1p. This response constitutes part of a morphogenesis checkpoint that couples cell cycle progression to proper bud formation, but the basis for the regulation of Swe1p degradation by the morphogenesis checkpoint remains unknown. Previous studies have identified a protein kinase, Hsl1p, and a phylogenetically conserved protein of unknown function, Hsl7p, as putative negative regulators of Swe1p. We report here that Hsl1p and Hsl7p act in concert to target Swe1p for degradation. Both proteins are required for Swe1p degradation during the unperturbed cell cycle, and excess Hsl1p accelerates Swe1p degradation in the G2-M phase. Hsl1p accumulates periodically during the cell cycle and promotes the periodic phosphorylation of Hsl7p. Hsl7p can be detected in a complex with Swe1p in cell lysates, and the overexpression of Hsl7p or Hsl1p produces an effective override of the G2arrest imposed by the morphogenesis checkpoint. These findings suggest that Hsl1p and Hsl7p interact directly with Swe1p to promote its recognition by the ubiquitination complex, leading ultimately to its destruction.

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PTTG has a Dual Role of Promotion-Inhibition in the Development of Pituitary Adenomas

Protein and Peptide Letters ◽

10.2174/0929866526666190722145449 ◽

2019 ◽

Vol 26 (11) ◽

pp. 800-818

Author(s):

Zujian Xiong ◽

Xuejun Li ◽

Qi Yang

Keyword(s):

Cell Cycle ◽

Pituitary Adenoma ◽

Pituitary Adenomas ◽

Cell Cycle Progression ◽

Key Factors ◽

Cycle Progression ◽

Sister Chromatids ◽

Regulation Of Cell Cycle ◽

Late Stages

Pituitary Tumor Transforming Gene (PTTG) of human is known as a checkpoint gene in the middle and late stages of mitosis, and is also a proto-oncogene that promotes cell cycle progression. In the nucleus, PTTG works as securin in controlling the mid-term segregation of sister chromatids. Overexpression of PTTG, entering the nucleus with the help of PBF in pituitary adenomas, participates in the regulation of cell cycle, interferes with DNA repair, induces genetic instability, transactivates FGF-2 and VEGF and promotes angiogenesis and tumor invasion. Simultaneously, overexpression of PTTG induces tumor cell senescence through the DNA damage pathway, making pituitary adenoma possessing the potential self-limiting ability. To elucidate the mechanism of PTTG in the regulation of pituitary adenomas, we focus on both the positive and negative function of PTTG and find out key factors interacted with PTTG in pituitary adenomas. Furthermore, we discuss other possible mechanisms correlate with PTTG in pituitary adenoma initiation and development and the potential value of PTTG in clinical treatment.

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Phosphorylation of RCC1 on Serine 11 Facilitates G1/S Transition in HPV E7-Expressing Cells

Biomolecules ◽

10.3390/biom11070995 ◽

2021 ◽

Vol 11 (7) ◽

pp. 995

Author(s):

Xiaoyan Hou ◽

Lijun Qiao ◽

Ruijuan Liu ◽

Xuechao Han ◽

Weifang Zhang

Keyword(s):

Cell Cycle ◽

Cervical Cancer ◽

Cell Cycle Regulation ◽

Cell Cycle Progression ◽

Mtor Pathway ◽

Cycle Progression ◽

Post Translational Modifications ◽

Hpv E7 ◽

Cycle Regulation

Persistent infection of high-risk human papillomavirus (HR-HPV) plays a causal role in cervical cancer. Regulator of chromosome condensation 1 (RCC1) is a critical cell cycle regulator, which undergoes a few post-translational modifications including phosphorylation. Here, we showed that serine 11 (S11) of RCC1 was phosphorylated in HPV E7-expressing cells. However, S11 phosphorylation was not up-regulated by CDK1 in E7-expressing cells; instead, the PI3K/AKT/mTOR pathway promoted S11 phosphorylation. Knockdown of AKT or inhibition of the PI3K/AKT/mTOR pathway down-regulated phosphorylation of RCC1 S11. Furthermore, S11 phosphorylation occurred throughout the cell cycle, and reached its peak during the mitosis phase. Our previous data proved that RCC1 was necessary for the G1/S cell cycle progression, and in the present study we showed that the RCC1 mutant, in which S11 was mutated to alanine (S11A) to mimic non-phosphorylation status, lost the ability to facilitate G1/S transition in E7-expressing cells. Moreover, RCC1 S11 was phosphorylated by the PI3K/AKT/mTOR pathway in HPV-positive cervical cancer SiHa and HeLa cells. We conclude that S11 of RCC1 is phosphorylated by the PI3K/AKT/mTOR pathway and phosphorylation of RCC1 S11 facilitates the abrogation of G1 checkpoint in HPV E7-expressing cells. In short, our study explores a new role of RCC1 S11 phosphorylation in cell cycle regulation.

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