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.

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 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 Alsterpaullone, a Cyclin-Dependent Kinase Inhibitor, Mediated Toxicity in HeLa Cells through Apoptosis-Inducing Effect

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Chunying Cui ◽  
Yuji Wang ◽  
Yaonan Wang ◽  
Ming Zhao ◽  
Shiqi Peng
Keyword(s):  
Cell Cycle ◽  
Hela Cells ◽  
Cell Cycle Progression ◽  
Caspase 3 ◽  
Kinase Inhibitor ◽  
Cdk Inhibitor ◽  
Cyclin Dependent Kinase ◽  
Cycle Progression ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Dose Dependent

Alsterpaullone, a small molecule cyclin-dependent kinase (CDK) inhibitor, regulates the cell cycle progression. Beyond death-inducing properties, we identified the effect of alsterpaullone on cycle procedure and apoptosis of HeLa cell. It was found that alsterpaullone inhibited HeLa cells in a time-dependent (0–72 h) and dose-dependent (0–30 μM) manner. In the presence of alsterpaullone, HeLa cells were arrested in G2/M prior to undergoing apoptosis via a mechanism that is involved in the regulation of various antiapoptotic genes, DNA-repair, transcription, and cell cycle progression. Compared to controls, alsterpaullone effectively prevented HeLa cells from entering S-phase. These potential therapeutic efficacies could be correlated with the activation of caspase-3.

scholarly journals Combination Gene Delivery of the Cell Cycle Inhibitor p27 with Thymidine Kinase Enhances Prodrug Cytotoxicity

1998 ◽  
Vol 72 (11) ◽  
pp. 9201-9207 ◽  
Author(s):  
Xavier Danthinne ◽  
Kazunori Aoki ◽  
Akiko L. Kurachi ◽  
Gary J. Nabel ◽  
Elizabeth G. Nabel
Keyword(s):  
Cell Cycle ◽  
Gene Transfer ◽  
Thymidine Kinase ◽  
Cell Cycle Progression ◽  
Kinase Inhibitor ◽  
Genetically Modified ◽  
Cyclin Dependent Kinase ◽  
Cycle Progression ◽  
Cyclin Dependent Kinase Inhibitor

ABSTRACT Cytoxicity induced by the herpesvirus thymidine kinase (TK) gene in combination with prodrugs is dependent on cell growth and leads to the elimination of genetically modified cells, thus limiting the duration of expression and efficacy of this treatment in vivo. Here, an effort was made to enhance TK/prodrug efficacy by coexpression of a cyclin-dependent kinase inhibitor (CKI), p27, to render cells resistant to TK/prodrug by inhibiting DNA synthesis. Expression of p27 by transfection substantially reduced cell cycle progression, and its activity was enhanced by mutations designed to stabilize the protein. Coexpression of p27 and TK or a p27/TK fusion protein led to greater prodrug cytotoxicity than that produced by TK alone in the Renca cell line, which is sensitive to bystander killing. Combination gene transfer of this CKI with TK therefore sustained the synthesis of TK by genetically modified cells to enhance the susceptibility of bystander cells to prodrug cytotoxicity and increased the efficacy of this gene transfer approach.

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