scholarly journals Cell cycle S-phase arrest drives cell extrusion

2019 ◽  
Author(s):  
Vivek K. Dwivedi ◽  
Carlos Pardo-Pastor ◽  
Rita Droste ◽  
Daniel P. Denning ◽  
Jody Rosenblatt ◽  
...  
Keyword(s):  
Cell Cycle ◽  
S Phase ◽  
C Elegans ◽  
Phase Arrest ◽  
Genome Wide ◽  
S Phase Arrest ◽  
Epithelial Cultures ◽  
A Cell ◽  
Cycle Dependent ◽  
Cell Extrusion

SUMMARYCell extrusion is a process of cell elimination in which a cell is squeezed out from its tissue of origin. Extrusion occurs in organisms as diverse as sponges, nematodes, insects, fish and mammals. Defective extrusion is linked to many epithelial disorders, including cancer. Despite broad occurrence, cell-intrinsic triggers of extrusion conserved across phyla are generally unknown. We combined genome-wide genetic screens with live-imaging studies of C. elegans embryos and mammalian epithelial cultures and found that S-phase arrest induced extrusion in both. Cells extruded from C. elegans embryos exhibited S-phase arrest, and RNAi treatments that specifically prevent S-phase entry or arrest blocked cell extrusion. Pharmacological induction of S-phase arrest was sufficient to promote cell extrusion from a canine epithelial monolayer. Thus, we have discovered an evolutionarily conserved cell-cycle-dependent trigger of cell extrusion. We suggest that S-phase-arrest induced cell extrusion plays a key role in physiology and disease.

scholarly journals ZFP36L2 is a cell cycle-regulated CCCH protein necessary for DNA lesion-induced S-phase arrest

Biology Open ◽  
2018 ◽  
Vol 7 (3) ◽  
pp. bio031575 ◽  
Author(s):  
Aya Noguchi ◽  
Shungo Adachi ◽  
Naoto Yokota ◽  
Tomohisa Hatta ◽  
Tohru Natsume ◽  
...  
Keyword(s):  
Cell Cycle ◽  
S Phase ◽  
Dna Lesion ◽  
Phase Arrest ◽  
S Phase Arrest ◽  
A Cell

Antimycin A as a mitochondria damage agent induces an S phase arrest of the cell cycle in HeLa cells

Life Sciences ◽  
2008 ◽  
Vol 83 (9-10) ◽  
pp. 346-355 ◽  
Author(s):  
Yong Hwan Han ◽  
Suhn Hee Kim ◽  
Sung Zoo Kim ◽  
Woo Hyun Park
Keyword(s):  
Cell Cycle ◽  
Hela Cells ◽  
S Phase ◽  
Antimycin A ◽  
Phase Arrest ◽  
S Phase Arrest

scholarly journals Inhibition of tumor cell growth by adenine is mediated by apoptosis induction and cell cycle S phase arrest

Oncotarget ◽  
2017 ◽  
Vol 8 (55) ◽  
pp. 94286-94296 ◽  
Author(s):  
Ming Han ◽  
Xin Cheng ◽  
Zhiqin Gao ◽  
Rongrong Zhao ◽  
Shizhuang Zhang
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Tumor Cell ◽  
S Phase ◽  
Tumor Cell Growth ◽  
Apoptosis Induction ◽  
Phase Arrest ◽  
S Phase Arrest

scholarly journals p21Cip1 and p27Kip1Regulate Cell Cycle Reentry after Hypoxic Stress but Are Not Necessary for Hypoxia-Induced Arrest

2001 ◽  
Vol 21 (4) ◽  
pp. 1196-1206 ◽  
Author(s):  
Susannah L. Green ◽  
Rachel A. Freiberg ◽  
Amato J. Giaccia
Keyword(s):  
Cell Cycle ◽  
Dna Synthesis ◽  
Kinase Inhibitors ◽  
S Phase ◽  
Hypoxic Stress ◽  
Cyclin Dependent Kinase ◽  
Low Oxygen ◽  
Double Knockout ◽  
Phase Arrest ◽  
S Phase Arrest

ABSTRACT We investigated the role of the cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1 in cell cycle regulation during hypoxia and reoxygenation. While moderate hypoxia (1 or 0.1% oxygen) does not significantly impair bromodeoxyuridine incorporation, at very low oxygen tensions (0.01% oxygen) DNA replication is rapidly shut down in immortalized mouse embryo fibroblasts. This S-phase arrest is intact in fibroblasts lacking the cyclin kinase inhibitors p21Cip1 and p27Kip1, indicating that these molecules are not essential elements of the arrest pathway. Hypoxia-induced arrest is accompanied by dephosphorylation of pRb and inhibition of cyclin-dependent kinase 2, which results in part from inhibitory phosphorylation. Interestingly, cells lacking the retinoblastoma tumor suppressor protein also display arrest under hypoxia, suggesting that pRb is not an essential mediator of this response. Upon reoxygenation, DNA synthesis resumes by 3.5 h and reaches aerobic levels by 6 h. Cells lacking p21, however, resume DNA synthesis more rapidly upon reoxygenation than wild-type cells, suggesting that this inhibitor may play a role in preventing premature reentry into the cell cycle upon cessation of the hypoxic stress. While p27 null cells did not exhibit rapid reentry into the cell cycle, cells lacking both p21 and p27 entered S phase even more aggressively than those lacking p21 alone, revealing a possible secondary role for p27 in this response. Cdk2 activity is also restored more rapidly in the double-knockout cells when returned to normoxia. These studies reveal that restoration of DNA synthesis after hypoxic stress, but not the S phase arrest itself, is regulated by p21 and p27.

Differential induction of ‘metabolic genes’ after mitogen stimulation and during normal cell cycle progression

1994 ◽  
Vol 107 (1) ◽  
pp. 241-252 ◽  
Author(s):  
C. Burger ◽  
M. Wick ◽  
S. Brusselbach ◽  
R. Muller
Keyword(s):  
Cell Cycle ◽  
Normal Cell ◽  
Cell Cycle Progression ◽  
S Phase ◽  
Cycle Progression ◽  
Genes Encoding ◽  
A Cell ◽  
Induced Genes ◽  
Cycle Dependent ◽  
Normal Cell Cycle

Mitogenic stimulation of quiescent cells not only triggers the cell division cycle but also induces an increase in cell volume, associated with an activation of cellular metabolism. It is therefore likely that genes encoding enzymes and other proteins involved in energy metabolism and biosynthetic pathways represent a major class of mitogen-induced genes. In the present study, we investigated in the non-established human fibroblast line WI-38 the induction by mitogens of 17 genes whose products play a role in different metabolic processes. We show that these genes fall into 4 different categories, i.e. non-induced genes, immediate early (IE) primary genes, delayed early (DE) secondary genes and late genes reaching peak levels in S-phase. In addition, we have analysed the regulation of these genes during normal cell cycle progression, using HL-60 cells separated by counterflow elutriation. A clear cell cycle regulation was seen with those genes that are induced in S-phase, i.e. thymidine kinase, thymidylate synthase and dihydrofolate reductase. In addition, two DE genes showed a cell cycle dependent expression. Ornithine decarboxylase mRNA increased around mid-G1, reaching maximum levels in S/G2, while hexokinase mRNA expression was highest in early G1. In contrast, the expression of other DE and IE genes did not fluctuate during the cell cycle, a result that was confirmed with elutriated WI-38 and serum-stimulated HL-60 cells. These observations suggest that G0-->S and G1-->S transition are distinct processes, exhibiting characteristic programmes of gene regulation, and merging around S-phase entry.

A Role for NIPA in DNA Damage Response.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1265-1265
Author(s):  
Christine von Klitzing ◽  
Florian Bassermann ◽  
Stephan W. Morris ◽  
Christian Peschel ◽  
Justus Duyster
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Phosphorylation Site ◽  
Genotoxic Stress ◽  
S Phase ◽  
Damage Response ◽  
A Cell ◽  
Cycle Dependent

Abstract The nuclear interaction partner of ALK (NIPA) is a nuclear protein identified by our group in a screen for NPM-ALK interaction partners. We recently reported that NIPA is an F-box protein that assembles with SKP1, Cul1 and Roc1 to establish a novel SCF-type E3 ubiquitin ligase. The formation of the SCFNIPA complex is regulated by cell cycle-dependent phosphorylation of NIPA that restricts SCFNIPA assembly from G1- to late S-phase, thus allowing its substrates to be active from late S-phase throughout mitosis. Proteins involved in cell cycle regulation frequently play a role in DNA damage checkpoints. We therefore sought to determine whether NIPA has a function in the cellular response to genotoxic stress. For this reason we treated NIH/3T3 cells with various DNA-damaging agents. Surprisingly, we observed phosphorylation of NIPA in response to some of these agents, including UV radiation. This phosphorylation was cell cycle phase independent and thus independent of the physiological cell cycle dependent phosphorylation of NIPA. The relevant phosphorylation site is identical to the respective site in the course of cell cycle-dependent phosphorylation of NIPA. Thus, phosphorylation of NIPA upon genotoxic stress would inactivate the SCFNIPA complex in a cell cycle independent manner. Interestingly, this phosphorylation site lies within a consensus site of the Chk1/Chk2 checkpoint kinases. These kinases are central to DNA damage checkpoint signaling. Chk1 is activated by ATR in response to blocked replication forks as they occur after treatment with UV. We performed experiments using the ATM/ATR inhibitor caffeine and the Chk1 inhibitor SB218078 to investigate a potential role of Chk1 in NIPA phosphorylation. Indeed, we found both inhibitors to prevent UV-induced phosphorylation of NIPA. Current experiments applying Chk1 knock-out cells will unravel the role of Chk1 in NIPA phosphorylation. Additional experiments were performed to investigate a function for NIPA in DNA-damage induced apoptosis. In this regard, we observed overexpression of NIPA WT to induce apoptosis in response to UV, whereas no proapoptotic effect was seen with the phosphorylation deficient NIPA mutant. Therefore, the phosphorylated form of NIPA may be involved in apoptotic signaling pathways. In summary, we present data suggesting a cell cycle independent function for NIPA. This activity is involved in DNA damage response and may be involved in regulating apoptosis upon genotoxic stress.

scholarly journals EGT2 gene transcription is induced predominantly by Swi5 in early G1.

1996 ◽  
Vol 16 (7) ◽  
pp. 3264-3274 ◽  
Author(s):  
B Kovacech ◽  
K Nasmyth ◽  
T Schuster
Keyword(s):  
Cell Cycle ◽  
Transcriptional Activation ◽  
Cell Separation ◽  
S Phase ◽  
Dependent Manner ◽  
Yeast Saccharomyces Cerevisiae ◽  
Concentration Dependent Manner ◽  
A Cell ◽  
Cycle Dependent ◽  
Ho Gene

In a screen for cell cycle-regulated genes in the yeast Saccharomyces cerevisiae, we have identified a gene, EGT2, which is involved in cell separation in the G1 stage of the cell cycle. Transcription of EGT2 is tightly regulated in a cell cycle-dependent manner. Transcriptional levels peak at the boundary of mitosis and early G1 The transcription factors responsible for EGT2 expression in early G1 are Swi5 and, to a lesser extent, Ace2. Swi5 is involved in the transcriptional activation of the HO gene during late G1 and early S phase, and Ace2 induces CTS1 transcription during early and late G1 We show that Swi5 activates EGT2 transcription as soon as it enters the nucleus at the end of mitosis in a concentration-dependent manner. Since Swi5 is unstable in the nucleus, its level drops rapidly, causing termination of EGT2 transcription before cells are committed to the next cell cycle. However, Swi5 is still able to activate transcription of HO in late G1 in conjunction with additional activators such as Swi4 and Swi6.

Methimazole inhibits FRTL5 thyroid cell proliferation by inducing S-phase arrest of the cell cycle.

Endocrinology ◽  
1993 ◽  
Vol 133 (5) ◽  
pp. 2403-2406 ◽  
Author(s):  
P Smerdely ◽  
V Pitsiavas ◽  
S C Boyages
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
S Phase ◽  
Thyroid Cell ◽  
Phase Arrest ◽  
S Phase Arrest

scholarly journals Cell Cycle Modulation by Marek’s Disease Virus: The Tegument Protein VP22 Triggers S-Phase Arrest and DNA Damage in Proliferating Cells

PLoS ONE ◽  
2014 ◽  
Vol 9 (6) ◽  
pp. e100004 ◽  
Author(s):  
Laëtitia Trapp-Fragnet ◽  
Djihad Bencherit ◽  
Danièle Chabanne-Vautherot ◽  
Yves Le Vern ◽  
Sylvie Remy ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Disease Virus ◽  
S Phase ◽  
Tegument Protein ◽  
Proliferating Cells ◽  
Phase Arrest ◽  
Cell Cycle Modulation ◽  
S Phase Arrest ◽  
Protein Vp22
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