scholarly journals Prenatal Octamethylcyclotetrasiloxane Exposure Impaired Proliferation of Neuronal Progenitor, Leading to Motor, Cognition, Social and Behavioral Functions

2021 ◽  
Vol 22 (23) ◽  
pp. 12949
Author(s):  
Dinh Nam Tran ◽  
Seon-Mi Park ◽  
Eui-Man Jung ◽  
Eui-Bae Jeung
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Kinase Inhibitor ◽  
Endocrine Disrupting Chemical ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Neuronal Progenitor ◽  
Neuronal Progenitors ◽  
Aberrant Gene Expression ◽  
Pregnant Mice ◽  
Aberrant Gene

Cyclic siloxane octamethylcyclotetrasiloxane (D4) has raised concerns as an endocrine-disrupting chemical (EDC). D4 is widely used in detergent products, cosmetics, and personal care products. Recently, robust toxicological data for D4 has been reported, but the adverse effects of D4 on brain development are unknown. Here, pregnant mice on gestational day 9.5 were treated daily with D4 to postnatal day 28, and the offspring mice were studied. The prenatal D4-treated mice exhibited cognitive dysfunction, limited memory, and motor learning defect. Moreover, prenatal D4 exposure reduced the proliferation of neuronal progenitors in the offspring mouse brain. Next, the mechanisms through which D4 regulated the cell cycle were investigated. Aberrant gene expression, such as cyclin-dependent kinases CDK6 and cyclin-dependent kinase inhibitor p27, were found in the prenatal D4-treated mice. Furthermore, the estrogen receptors ERa and ERb were increased in the brain of prenatal D4-treated mice. Overall, these findings suggest that D4 exerts estrogen activity that affects the cell cycle progression of neuronal progenitor cells during neurodevelopment, which may be associated with cognitive deficits in offspring.

scholarly journals Prenatal Octamethylcyclotetrasiloxane Exposure Impaired Proliferation of Neuronal Progenitor, Leading to Motor, Cognition, Social and Behavioral Functions

2021 ◽  
Author(s):  
Dinh Nam Tran ◽  
Seon-Mi Park ◽  
Eui-Man Jung ◽  
Eui-Bae Jeung
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Kinase Inhibitor ◽  
Endocrine Disrupting Chemical ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Neuronal Progenitor ◽  
Neuronal Progenitors ◽  
Aberrant Gene Expression ◽  
Pregnant Mice ◽  
Aberrant Gene

Abstract Cyclic siloxane octamethylcyclotetrasiloxane (D4) is an endocrine-disrupting chemical (EDC) used widely in detergent products, cosmetics, and personal care products. Recently, robust toxicological data for D4 has been reported, but the adverse effects of D4 on brain development are unknown. Here, pregnant mice on a gestational day 9.5 were treated daily with D4 to postnatal day 28, and the offspring mice were studied. The prenatal D4-treated mice exhibited cognitive dysfunction, limited memory, and motor learning defect. Moreover, prenatal D4 exposure reduced the proliferation of neuronal progenitors in the offspring mouse brain. Next, the mechanism(s) through which D4 regulated the cell cycle was investigated. Aberrant gene expression, such as cyclin-dependent kinases CDK6 and cyclin-dependent kinase inhibitor p27, was found in the prenatal D4-treated mice. Furthermore, estrogen receptor ERa and ERb increased in the brain of prenatal D4-treated mice. Overall, these findings suggest that D4 exerts estrogen activity that affects the cell cycle progression of neuronal progenitor cells during neurodevelopment, which may be associated with cognitive deficits in offspring.

Paradoxical accumulation of the cyclin-dependent kinase inhibitor p27kip1 during the cAMP-dependent mitogenic stimulation of thyroid epithelial cells

1996 ◽  
Vol 109 (7) ◽  
pp. 1759-1764
Author(s):  
F. Depoortere ◽  
J.E. Dumont ◽  
P.P. Roger
Keyword(s):  
Cell Cycle ◽  
Epithelial Cells ◽  
Cell Cycle Progression ◽  
Kinase Inhibitor ◽  
Concomitant Administration ◽  
Growth Stimulation ◽  
Positive Control ◽  
Cycle Progression ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Enhanced Expression

In different systems, cAMP either blocks or promotes cell cycle progression in mid to late G1 phase. Dog thyroid epithelial cells in primary culture constitute a model of positive control of DNA synthesis initiation and G0-S pre-replicative phase progression by cyclic AMP (cAMP) as a second messenger for thyrotropin (TSH). We report here that TSH markedly increases the expression of p27kip1, the inhibitor of the cell cycle and cyclin-dependent kinases. This effect was prevented by the concomitant administration of the cAMP-independent mitogens, epidermal growth factor (EGF)+serum. EGF+serum also slightly inhibited the weak basal accumulation of p27kip1. Nevertheless, in the case of stimulation by TSH alone, the cAMP-dependent cell cycle progression was fully compatible with the enhanced expression of p27kip1. This observation is paradoxical since a decrease of p27kip1 is generally associated with growth stimulation in other systems, and since a similar cAMP-dependent increase of p27kip1 in macrophages has been found responsible for mid-G1 cell cycle arrest. The opposite regulation of p27kip1 in response to TSH or EGF+serum in dog thyroid epithelial cells suggests a major difference at mid to late G1 stages between cAMP-dependent and cAMP-independent mitogenic pathways.

scholarly journals MicroRNAs in the miR-106b Family Regulate p21/CDKN1A and Promote Cell Cycle Progression

2008 ◽  
Vol 28 (7) ◽  
pp. 2167-2174 ◽  
Author(s):  
Irena Ivanovska ◽  
Alexey S. Ball ◽  
Robert L. Diaz ◽  
Jill F. Magnus ◽  
Miho Kibukawa ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Kinase Inhibitor ◽  
Phenotype Microarray ◽  
Loss Of Function ◽  
Cycle Progression ◽  
Multiple Tumor ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Expression Of Genes ◽  
Tumor Types

ABSTRACT microRNAs in the miR-106b family are overexpressed in multiple tumor types and are correlated with the expression of genes that regulate the cell cycle. Consistent with these observations, miR-106b family gain of function promotes cell cycle progression, whereas loss of function reverses this phenotype. Microarray profiling uncovers multiple targets of the family, including the cyclin-dependent kinase inhibitor p21/CDKN1A. We show that p21 is a direct target of miR-106b and that its silencing plays a key role in miR-106b-induced cell cycle phenotypes. We also show that miR-106b overrides a doxorubicin-induced DNA damage checkpoint. Thus, miR-106b family members contribute to tumor cell proliferation in part by regulating cell cycle progression and by modulating checkpoint functions.

GATA-2 Controls Proliferation of Megakaryocyte Progenitors and Its Expression Contributes to Human DS-AMKL.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1380-1380
Author(s):  
Zan Huang ◽  
John Crispino
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Blast Crisis ◽  
Myelogenous Leukemia ◽  
Chromosome 21 ◽  
Cell Cycle Regulators ◽  
Megakaryoblastic Leukemia ◽  
Aberrant Gene Expression ◽  
Genome Wide ◽  
Aberrant Gene

Abstract GATA2 is an essential transcription factor that regulates multiple aspects of hematopoiesis. Mutations in GATA2 are associated with blast crisis phase of chronic myelogenous leukemia (CML) while overexpression of GATA2 is a hallmark of Down syndrome acute megakaryoblastic leukemia (DS-AMKL), a malignancy that is defined by the combination of trisomic chromosome 21 and a GATA1 mutation. Here, we show thatGATA2 is essential for megakaryocyte development from both wild-type and GATA-1mutant hematopoietic progenitors. Furthermore, we reveal that GATA2 is indispensable for cell cycle progression and that its expression cooperates with activated JAK3 to promote TPO-independent expansion of megakaryocytes. Genome-wide microarray analysis revealed that GATA2 regulates a wide set of genes including cell cycle regulators and lineage-specific genes that are essential for terminal differentiation of megakaryocytes. Of note, a subset of genes within the GATA2 signature is contained within human DS-AMKL patient specimens. These observations implicate overexpression of GATA2 in the aberrant gene expression and proliferation of AMKL. Taken together, our data demonstrate thatGATA2 is a critical regulator of normal and malignant megakaryopoiesis.

scholarly journals Transcriptional Downregulation of p27KIP1 through Regulation of E2F Function during LMP1-Mediated Transformation

2009 ◽  
Vol 83 (24) ◽  
pp. 12671-12679 ◽  
Author(s):  
David N. Everly ◽  
Bernardo A. Mainou ◽  
Nancy Raab-Traub
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Kinase Inhibitor ◽  
Cyclin Dependent Kinase ◽  
Mobility Shift ◽  
Cycle Progression ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Phenotypic Transformation ◽  
Electrophoretic Mobility Shift Assays ◽  
Posttranscriptional Level

ABSTRACT LMP1 induces the phenotypic transformation of fibroblasts and affects regulators of the cell cycle during this process. LMP1 decreases expression of the cyclin-dependent kinase inhibitor p27 and increases the levels and phosphorylation of cyclin-dependent kinase 2 and the retinoblastoma protein. In the present study, the effects of LMP1 on cell cycle progression and the mechanism of p27 downregulation by LMP1 were determined. Although p27 is frequently regulated at the posttranscriptional level during cell cycle progression and in cancer, LMP1 did not decrease ectopically expressed p27. However, LMP1 did decrease p27 RNA levels and inhibited the activity of p27 promoter reporters. The LMP1-regulated promoter element was mapped to a region containing two E2F sites. Electrophoretic mobility shift assays determined that the regulated cis element bound an inhibitory E2F complex containing E2F4 and p130. These findings indicate that LMP1 decreases p27 transcription through effects on E2F family transcription factors. This property likely contributes to the ability of LMP1 to stimulate cell cycle progression.

scholarly journals FOXO target gene CTDSP2 regulates cell cycle progression through Ras and p21Cip1/Waf1

2015 ◽  
Vol 469 (2) ◽  
pp. 289-298 ◽  
Author(s):  
David E.A. Kloet ◽  
Paulien E. Polderman ◽  
Astrid Eijkelenboom ◽  
Lydia M. Smits ◽  
Miranda H. van Triest ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Kinase Inhibitor ◽  
Cyclin Dependent Kinase ◽  
Cycle Progression ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Altered Gene Expression ◽  
Forkhead Box ◽  
Altered Gene ◽  
Regulate Cell Cycle Progression

Growth factor controlled activity of forkhead box O transcription factors results in altered gene expression, including expression of CTDSP2 (C-terminal domain small phosphatase 2). CTDSP2 can regulate cell cycle progression through Ras and the cyclin-dependent kinase inhibitor p21Cip1/Waf1.

scholarly journals CCNE1 and E2F1 Partially Suppress G1 Phase Arrest Caused by Spliceostatin A Treatment

2021 ◽  
Vol 22 (21) ◽  
pp. 11623
Author(s):  
Kei Kikuchi ◽  
Daisuke Kaida
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Kinase Inhibitor ◽  
G1 Phase ◽  
Cell Cycle Regulators ◽  
Protein Levels ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Phase Arrest ◽  
G1 Phase Arrest ◽  
Spliceostatin A

The potent splicing inhibitor spliceostatin A (SSA) inhibits cell cycle progression at the G1 and G2/M phases. We previously reported that upregulation of the p27 cyclin-dependent kinase inhibitor encoded by CDKN1B and its C-terminal truncated form, namely p27*, which is translated from CDKN1B pre-mRNA, is one of the causes of G1 phase arrest caused by SSA treatment. However, the detailed molecular mechanism underlying G1 phase arrest caused by SSA treatment remains to be elucidated. In this study, we found that SSA treatment caused the downregulation of cell cycle regulators, including CCNE1, CCNE2, and E2F1, at both the mRNA and protein levels. We also found that transcription elongation of the genes was deficient in SSA-treated cells. The overexpression of CCNE1 and E2F1 in combination with CDKN1B knockout partially suppressed G1 phase arrest caused by SSA treatment. These results suggest that the downregulation of CCNE1 and E2F1 contribute to the G1 phase arrest induced by SSA treatment, although they do not exclude the involvement of other factors in SSA-induced G1 phase arrest.

Sign in / Sign up

Export Citation Format

Share Document