S-phase-specific expression of the Mad3 gene in proliferating and differentiating cells

2001 ◽  
Vol 359 (2) ◽  
pp. 361-367 ◽  
Author(s):  
Elizabeth J. FOX ◽  
Stephanie C. WRIGHT
Keyword(s):  
Cell Cycle ◽  
Cellular Proliferation ◽  
Cultured Cells ◽  
S Phase ◽  
Proliferating Cells ◽  
Specific Expression ◽  
Related Function ◽  
Erythroleukemia Cells ◽  
A Cell ◽  
Pass Through

The Myc/Max/Mad transcription factor network plays a central role in the control of cellular proliferation, differentiation and apoptosis. In order to elucidate the biological function of Mad3, we have analysed the precise temporal patterns of Mad3 mRNA expression during the cell cycle and differentiation in cultured cells. We show that Mad3 is induced at the G1/S transition in proliferating cells; expression persists throughout S-phase, and then declines as cells pass through G2 and mitosis. The expression pattern of Mad3 is coincident with that of Cdc2 throughout the cell cycle. In contrast, the expression of Mad3 during differentiation of cultured mouse erythroleukemia cells shows two transient peaks of induction. The first of these occurs at the onset of differentiation, and does not correlate with the S-phase of the cell cycle, whereas the second is coincident with the S-phase burst that precedes the terminal stages of differentiation. Our results therefore suggest that Mad3 serves a cell-cycle-related function in both proliferating and differentiating cells, and that it may also have a distinct role at various stages of differentiation.

Temporal and spatial expression of the cell-cycle regulator cul-1 in Drosophila and its stimulation by radiation-induced apoptosis

2000 ◽  
Vol 203 (18) ◽  
pp. 2747-2756 ◽  
Author(s):  
V. Filippov ◽  
M. Filippova ◽  
F. Sehnal ◽  
S.S. Gill
Keyword(s):  
Phase Transition ◽  
Cell Cycle ◽  
Cultured Cells ◽  
Lethal Dose ◽  
S Phase ◽  
Model Organisms ◽  
Cell Cycle Regulators ◽  
Protein Levels ◽  
Pass Through ◽  
Induced Apoptosis

Cul-1 protein is part of the ubiquitin ligase complex that is conserved from yeast to humans. This complex specifically marks cell-cycle regulators for their subsequent destruction. Two null mutations of the cul-1 gene are known, in budding yeast and in nematodes. Although in both these organisms the cul-1 gene executes essentially the same function, the manifestation of its lack-of-function mutations differs considerably. In yeast the mutation causes arrest at the G(1)/S-phase transition, whereas in nematodes excessive cell divisions occur because mutant cells are unable to exit the mitotic cycle. We isolated cul-1 orthologues from two model organisms, Drosophila melanogaster and mouse. We show that the Drosophila full-length cul-1 gene restores the yeast mutant's inability to pass through the G(1)/S-phase transition. We also characterize expression of this gene at the transcript and protein levels during Drosophila development and show that cul-1 gene is maternally supplied as a protein, but not as an RNA transcript. Zygotic transcription of the gene, however, resumes at early stages of embryogenesis. We also found an increase in cul-1 transcription in cultured cells treated with a lethal dose of gamma-irradiation.

scholarly journals A protein synthesis-dependent increase in E2F1 mRNA correlates with growth regulation of the dihydrofolate reductase promoter.

1993 ◽  
Vol 13 (3) ◽  
pp. 1610-1618 ◽  
Author(s):  
J E Slansky ◽  
Y Li ◽  
W G Kaelin ◽  
P J Farnham
Keyword(s):  
Cell Cycle ◽  
Protein Synthesis ◽  
Phase Boundary ◽  
Dihydrofolate Reductase ◽  
Transcription Initiation ◽  
Growth Regulation ◽  
Cellular Proliferation ◽  
Protein S ◽  
S Phase ◽  
Dependent Manner

Enhanced expression of genes involved in nucleotide biosynthesis, such as dihydrofolate reductase (DHFR), is a hallmark of entrance into the DNA synthesis (S) phase of the mammalian cell cycle. To investigate the regulated expression of the DHFR gene, we stimulated serum-starved NIH 3T3 cells to synchronously reenter the cell cycle. Our previous results show that a cis-acting element at the site of DHFR transcription initiation is necessary for serum regulation. Recently, this element has been demonstrated to bind the cloned transcription factor E2F. In this study, we focused on the role of E2F in the growth regulation of DHFR. We demonstrated that a single E2F site, in the absence or presence of other promoter elements, was sufficient for growth-regulated promoter activity. Next, we showed that the increase in DHFR mRNA at the G1/S-phase boundary required protein synthesis, raising the possibility that a protein(s) lacking in serum-starved cells is required for DHFR transcription. We found that, similar to DHFR mRNA expression, levels of murine E2F1 mRNA were low in serum-starved cells and increased at the G1/S-phase boundary in a protein synthesis-dependent manner. Furthermore, in a cotransfection experiment, expression of human E2F1 stimulated the DHFR promoter 22-fold in serum-starved cells. We suggest that E2F1 may be the key protein required for DHFR transcription that is absent in serum-starved cells. Expression of E2F also abolished the serum-stimulated regulation of the DHFR promoter and resulted in transcription patterns similar to those seen with expression of the adenoviral oncoprotein E1A. In summary, we provide evidence for the importance of E2F in the growth regulation of DHFR and suggest that alterations in the levels of E2F may have severe consequences in the control of cellular proliferation.

scholarly journals JunB Breakdown in Mid-/Late G2 Is Required for Down-Regulation of Cyclin A2 Levels and Proper Mitosis

2008 ◽  
Vol 28 (12) ◽  
pp. 4173-4187 ◽  
Author(s):  
Rosa Farràs ◽  
Véronique Baldin ◽  
Sandra Gallach ◽  
Claire Acquaviva ◽  
Guillaume Bossis ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Suppressor ◽  
Genetic Instability ◽  
S Phase ◽  
Subsequent Reduction ◽  
Suppressor Activity ◽  
Cell Synchronization ◽  
Tumor Suppressor Activity ◽  
A Cell ◽  
Cyclin A2

ABSTRACT JunB, a member of the AP-1 family of dimeric transcription factors, is best known as a cell proliferation inhibitor, a senescence inducer, and a tumor suppressor, although it also has been attributed a cell division-promoting activity. Its effects on the cell cycle have been studied mostly in G1 and S phases, whereas its role in G2 and M phases still is elusive. Using cell synchronization experiments, we show that JunB levels, which are high in S phase, drop during mid- to late G2 phase due to accelerated phosphorylation-dependent degradation by the proteasome. The forced expression of an ectopic JunB protein in late G2 phase indicates that JunB decay is necessary for the subsequent reduction of cyclin A2 levels in prometaphase, the latter event being essential for proper mitosis. Consistently, abnormal JunB expression in late G2 phase entails a variety of mitotic defects. As these aberrations may cause genetic instability, our findings contrast with the acknowledged tumor suppressor activity of JunB and reveal a mechanism by which the deregulation of JunB might contribute to tumorigenesis.

scholarly journals Terminal differentiation of ectodermal epithelial stem cells of Hydra can occur in G2 without requiring mitosis or S phase.

1990 ◽  
Vol 110 (4) ◽  
pp. 939-945 ◽  
Author(s):  
S Dübel ◽  
H C Schaller
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Epithelial Cells ◽  
Terminal Differentiation ◽  
S Phase ◽  
Epithelial Stem Cells ◽  
Proliferating Cells ◽  
Specific Differentiation ◽  
G2 Phase

Using bromodeoxyuridine incorporation to label cells in S phase we found that ectodermal epithelial cells of Hydra can start and complete their terminal differentiation in the G2 phase of the cell cycle. Most of the cells traversed their last S phase before the signal for differentiation, namely excision of head or foot, was given. The S phase inhibitor aphidicolin accordingly did not inhibit head or foot specific differentiation. The results show that differentiation to either head- or foot-specific ectodermal epithelial cells can start and is completed within the same G2 phase. This is therefore the first description of a complete differentiation from a population of proliferating cells to terminally differentiated, cell cycle-arrested cells without the necessity of passing through an S phase or mitosis.

scholarly journals The INO80 complex activates the transcription of S‐phase genes in a cell cycle‐regulated manner

FEBS Journal ◽  
2018 ◽  
Vol 285 (20) ◽  
pp. 3870-3881 ◽  
Author(s):  
Iva Knezevic ◽  
Alberto González‐Medina ◽  
Laura Gaspa ◽  
Elena Hidalgo ◽  
José Ayté
Keyword(s):  
Cell Cycle ◽  
S Phase ◽  
A Cell

Cyclin Dependent Kinases and Regulation of the Fission Yeast Cell Cycle

1999 ◽  
Vol 380 (7-8) ◽  
pp. 729-733 ◽  
Author(s):  
P. Nurse
Keyword(s):  
Cell Cycle ◽  
Yeast Cell ◽  
Fission Yeast ◽  
S Phase ◽  
Yeast Cell Cycle ◽  
Cyclin Dependent Kinases ◽  
Fission Yeast Cell ◽  
Nutritional Deprivation ◽  
Orderly Fashion ◽  
A Cell

AbstractThe cyclin dependent kinases (CDKs), formed by complexes between Cdc2p and the B-cyclins Cig2p and Cdc13p, have a central role in regulating the fission yeast cell cycle and maintaining genomic stability. The CDK Cig2p/Cdc2p controls the onset of S-phase and the CDK Cdc13p/Cdc2p controls the onset of mitosis and ensures that there is only one S-phase in each cell. Cdc13p/Cdc2p can replace Cig2p/Cdc2p for the onset of S-phase, suggesting that the increasing activity of a single CDK during the cell cycle is sufficient to drive a cell in an orderly fashion into S-phase and into mitosis. If S-phase is incomplete, then inhibition of Cdc13p/Cdc2p prevents cells with unreplicated DNA from undergoing a catastrophic entry into mitosis. Control of CDK activity is also important to allow cells to exit the cell cycle and accumulate in G1 in response to nutritional deprivation and the presence of pheromone.

scholarly journals Targeted Deletion of the S-Phase-Specific Myc Antagonist Mad3 Sensitizes Neuronal and Lymphoid Cells to Radiation-Induced Apoptosis

2001 ◽  
Vol 21 (3) ◽  
pp. 703-712 ◽  
Author(s):  
Christophe Quéva ◽  
Grant A. McArthur ◽  
Brian M. Iritani ◽  
Robert N. Eisenman
Keyword(s):  
Cell Cycle ◽  
Progenitor Cells ◽  
Cellular Response ◽  
Leucine Zipper ◽  
Neural Progenitor Cells ◽  
Expression Patterns ◽  
S Phase ◽  
Lymphoid Cells ◽  
Cell Cycle Exit ◽  
Proliferating Cells

ABSTRACT The Mad family comprises four basic-helix-loop-helix/leucine zipper proteins, Mad1, Mxi1, Mad3, and Mad4, which heterodimerize with Max and function as transcriptional repressors. The balance between Myc-Max and Mad-Max complexes has been postulated to influence cell proliferation and differentiation. The expression patterns of Mad family genes are complex, but in general, the induction of most family members is linked to cell cycle exit and differentiation. The expression pattern ofmad3 is unusual in that mad3 mRNA and protein were found to be restricted to proliferating cells prior to differentiation. We show here that during murine developmentmad3 is specifically expressed in the S phase of the cell cycle in neuronal progenitor cells that are committed to differentiation. To investigate mad3 function, we disrupted the mad3 gene by homologous recombination in mice. No defect in cell cycle exit and differentiation could be detected inmad3 homozygous mutant mice. However, upon gamma irradiation, increased cell death of thymocytes and neural progenitor cells was observed, implicating mad3 in the regulation of the cellular response to DNA damage.

scholarly journals The Human Cytomegalovirus UL82 Gene Product (pp71) Accelerates Progression through the G1 Phase of the Cell Cycle

2003 ◽  
Vol 77 (6) ◽  
pp. 3451-3459 ◽  
Author(s):  
Robert F. Kalejta ◽  
Thomas Shenk
Keyword(s):  
Cell Cycle ◽  
Human Cytomegalovirus ◽  
Cell Cycle Progression ◽  
Protein Product ◽  
S Phase ◽  
Quiescent Cells ◽  
A Cell ◽  
Infected Cells ◽  
The One ◽  
Infectious Cycle

ABSTRACT As viruses are reliant upon their host cell to serve as proper environments for their replication, many have evolved mechanisms to alter intracellular conditions to suit their own needs. For example, human cytomegalovirus induces quiescent cells to enter the cell cycle and then arrests them in late G1, before they enter the S phase, a cell cycle compartment that is presumably favorable for viral replication. Here we show that the protein product of the human cytomegalovirus UL82 gene, pp71, can accelerate the movement of cells through the G1 phase of the cell cycle. This activity would help infected cells reach the late G1 arrest point sooner and thus may stimulate the infectious cycle. pp71 also induces DNA synthesis in quiescent cells, but a pp71 mutant protein that is unable to induce quiescent cells to enter the cell cycle still retains the ability to accelerate the G1 phase. Thus, the mechanism through which pp71 accelerates G1 cell cycle progression appears to be distinct from the one that it employs to induce quiescent cells to exit G0 and subsequently enter the S phase.

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