scholarly journals Mad4 is regulated by a transcriptional repressor complex that contains Miz-1 and c-Myc

2003 ◽  
Vol 370 (1) ◽  
pp. 291-298 ◽  
Author(s):  
Louise KIME ◽  
Stephanie C. WRIGHT
Keyword(s):  
Transcriptional Repression ◽  
Cellular Proliferation ◽  
Core Promoter ◽  
Core Promoter Region ◽  
Differentiated Cells ◽  
Chemically Induced ◽  
Proliferation And Differentiation ◽  
Repressor Complex ◽  
Undifferentiated Cells ◽  
Novel Target

Myc and Mad family proteins are central regulators of cellular proliferation and differentiation. We show that various Mad family genes have distinct patterns of expression during the chemically induced differentiation of mouse erythroleukaemia (MEL) cells, suggesting that they each serve a different function. Mad4 RNA is highly induced and persists in terminally differentiated cells, in agreement with observations in other systems. Using reporter gene assays in stably transfected MEL cells, we show that induction of Mad4 is mediated by a 49nt core promoter region. We demonstrate that the initiator element is required for Mad4 activation, and show that induction is associated with the loss from the initiator of a complex that contains Miz-1 and c-Myc. Miz-1 activates the Mad4 promoter in transient transfection assays, and this effect is antagonized by c-Myc. We therefore identify Mad4 as a novel target of transcriptional repression by c-Myc. These data suggest that the expression of Mad4 in proliferating undifferentiated cells is suppressed by the binding of a c-Myc—Miz-1 repressor complex at the initiator, and that the activation of Mad4 during differentiation results, at least in part, from a decrease in c-Myc-mediated repression.

scholarly journals The winged-helix/forkhead protein myocyte nuclear factor β (MNF-β) forms a co-repressor complex with mammalian Sin3B

2000 ◽  
Vol 345 (2) ◽  
pp. 335-343 ◽  
Author(s):  
Quan YANG ◽  
Yanfeng KONG ◽  
Beverly ROTHERMEL ◽  
Daniel J. GARRY ◽  
Rhonda BASSEL-DUBY ◽  
...  
Keyword(s):  
Gene Family ◽  
Transcriptional Repression ◽  
Growth Regulation ◽  
Cellular Proliferation ◽  
Precursor Cells ◽  
Nuclear Factor ◽  
Winged Helix ◽  
Repressor Complex ◽  
Myocyte Nuclear Factor ◽  
Myogenic Precursor

Winged-helix/forkhead proteins regulate developmental events in both invertebrate and vertebrate organisms, but biochemical functions that establish a mechanism of action have been defined for only a few members of this extensive gene family. Here we demonstrate that MNF (myocyte nuclear factor)-β, a winged-helix protein expressed selectively and transiently in myogenic precursor cells of the heart and skeletal muscles, collaborates with proteins of the mammalian Sin3 (mSin3) family to repress transcription. Mutated forms of MNF-β that fail to bind mSin3 are defective in transcriptional repression and in negative growth regulation, an overexpression phenotype revealed in oncogenic transformation assays. These data extend the known repertoire of transcription factors with which mSin3 proteins can function as co-repressors to include members of the winged-helix gene family. Transcriptional repression by MNF-β-mSin3 complexes may contribute to the co-ordination of cellular proliferation and terminal differentiation of myogenic precursor cells.

scholarly journals Erythropoietin-induced stimulation of differentiation and proliferation in J2E cells is not mimicked by chemical induction

Blood ◽  
1992 ◽  
Vol 80 (2) ◽  
pp. 412-419 ◽  
Author(s):  
SJ Busfield ◽  
SP Klinken
Keyword(s):  
Cell Line ◽  
Messenger Rna ◽  
Cellular Proliferation ◽  
Erythroid Cell ◽  
Chemical Induction ◽  
Chemically Induced ◽  
Proliferation And Differentiation ◽  
Differentiation And Proliferation ◽  
Sudden Decrease ◽  
Physiologic Stimulus

The J2E cell line is a novel erythroid cell line that differentiates in response to erythropoietin (Epo), the physiologic stimulus for erythropoiesis. After exposure to Epo, the cells synthesize hemoglobin, and we show here that this process is tightly linked to increases in cellular proliferation and DNA synthesis. The hormone-induced terminal differentiation also results in morphologic alterations and the accumulation of transcripts for alpha, beta maj, and beta min globins. c-myc messenger RNA levels increase rapidly after exposure to Epo and precede the increase in cell division, while c-myb undergoes a transient decrease. Differentiation of J2E cells can also be achieved with sodium butyrate, but, in contrast with Epo, this is associated with a retardation of replication and a sudden decrease in c-myc levels. These results show that, in this system, chemically induced differentiation differs from terminal maturation promoted by Epo and that the processes of proliferation and differentiation in J2E cells can be uncoupled.

scholarly journals Erythropoietin-induced stimulation of differentiation and proliferation in J2E cells is not mimicked by chemical induction

Blood ◽  
1992 ◽  
Vol 80 (2) ◽  
pp. 412-419 ◽  
Author(s):  
SJ Busfield ◽  
SP Klinken
Keyword(s):  
Cell Line ◽  
Messenger Rna ◽  
Cellular Proliferation ◽  
Erythroid Cell ◽  
Chemical Induction ◽  
Chemically Induced ◽  
Proliferation And Differentiation ◽  
Differentiation And Proliferation ◽  
Sudden Decrease ◽  
Physiologic Stimulus

Abstract The J2E cell line is a novel erythroid cell line that differentiates in response to erythropoietin (Epo), the physiologic stimulus for erythropoiesis. After exposure to Epo, the cells synthesize hemoglobin, and we show here that this process is tightly linked to increases in cellular proliferation and DNA synthesis. The hormone-induced terminal differentiation also results in morphologic alterations and the accumulation of transcripts for alpha, beta maj, and beta min globins. c-myc messenger RNA levels increase rapidly after exposure to Epo and precede the increase in cell division, while c-myb undergoes a transient decrease. Differentiation of J2E cells can also be achieved with sodium butyrate, but, in contrast with Epo, this is associated with a retardation of replication and a sudden decrease in c-myc levels. These results show that, in this system, chemically induced differentiation differs from terminal maturation promoted by Epo and that the processes of proliferation and differentiation in J2E cells can be uncoupled.

β-PVDF Membranes Induce Cellular Proliferation and Differentiation in Static and Dynamic Conditions

2008 ◽  
Vol 587-588 ◽  
pp. 72-76 ◽  
Author(s):  
M.T. Rodrigues ◽  
Manuela E. Gomes ◽  
João F. Mano ◽  
Rui L. Reis
Keyword(s):  
Polyvinylidene Fluoride ◽  
Cellular Proliferation ◽  
Bone Marrow Cells ◽  
Culture Conditions ◽  
Cellular Behavior ◽  
Cellular Attachment ◽  
Proliferation And Differentiation ◽  
Undifferentiated Cells ◽  
Marrow Cells

Bone marrow cells are a potential source to induce different lineage cells which can be used to rebuild or replace damaged tissues using a Tissue Engineering (TE) approach. However, TE strategies usually require the use of a material to support the development of a biological tissue. Beta-polyvinylidene fluoride (β-PVDF) is a biocompatible, thermoplastic with piezo-electrical properties that has been shown to provide a good cellular attachment and therefore might present advantageous properties as a scaffold material for cell seeding/culturing. The present study describes the characterization of β-PVDF membranes as a support material for growth and differentiation of goat marrow cells (GMCs) into osteoblasts, leading to the formation of substitutes for tissue regeneration. The obtained results suggest that β-PVDF piezoelectric properties influence cellular behavior. β- PVDF membranes not only enhance GMCs adherence and proliferation but also improve differentiation towards the osteogenic phenotype both in static and dynamic culture conditions. Furthermore, β-PVDF membranes exhibit very promising properties, suggesting that this material provides adequate support for the seeding and the development of undifferentiated cells towards a desired phenotype.

scholarly journals Nutritional Stimulation by In-ovo Feeding Modulates Cellular Proliferation and Differentiation in the Small Intestinal Epithelium of Chicks

2021 ◽  
Author(s):  
Naama Reicher ◽  
Tal Melkman-Zehavi ◽  
Jonathan Dayan ◽  
Eric A. Wong ◽  
Zehava Uni
Keyword(s):  
Goblet Cell ◽  
Cellular Proliferation ◽  
In Ovo ◽  
Treatment Groups ◽  
Differentiated Cells ◽  
Cell Counts ◽  
Proliferation And Differentiation ◽  
Cell Densities ◽  
In Ovo Feeding ◽  
The Impact

Abstract BackgroundNutritional stimulation of the small intestine (SI) of chick embryos can be conducted by enriching the amniotic fluid with nutrients via the in-ovo feeding (IOF) methodology. The impact of IOF of specific nutrients on cellular proliferation and differentiation within the multipotent (MP) and differentiated cell niches of the developing SI have not yet been characterized. In the study, we examined the effects of IOF of 1% glutamine (IOF-Gln), 1% leucine (IOF-Leu) and 0.4% NaCl (IOF-NaCl), compared to non-injected controls, on the proportions and localizations of MP, progenitor and differentiated cells within the SI epithelium of peri-hatch chicks. MP, progenitor and differentiated cells were located and quantified in jejunum sections of all treatment groups at E17 and at E19, and post-hatch at days 0, 1, 3 and 7, by immunofluorescence of Sox9 and PCNA, in-situ hybridization of Lgr5 and PepT1 and histochemical goblet cell staining.ResultsAt E19, 48 h post IOF, the effects of IOF treatments, in comparison to Control embryos, were as follows: total cell counts increased by 40%, 33% and 19%, and MP cell counts increased by 52%, 50% and 38%, in IOF-Gln, IOF-Leu and IOF-NaCl embryos, respectively. Only IOF-Gln embryos exhibited a significant, 36% increase in progenitor cell counts. Lgr5+ stem cell localizations shifted to villus bottoms in IOF-treated embryos. The differentiated, PepT1+ region of the villi was 1.9 and 1.3-fold longer in IOF-Gln and IOF-Leu embryos, respectively, while goblet cell densities decreased by 20% in IOF-Gln embryos. Between hatch and D7, crypt and villi epithelial cell counts were significantly higher IOF-Gln chicks, compared to Control chicks (P<0.05).ConclusionsIOF promotes pre-hatch SI maturation through increased proportions and enhanced compartmentalization of the MP and differentiated cell niches. IOF of glutamine stimulates SI maturation to a greater extent than leucine and NaCl, and elicits further expansions of the crypt and villus epithelium during the first week post-hatch. These findings shed light on the link between primary nutritional stimulation and cellular maturation within the SI epithelium.

scholarly journals PC12 and THP-1 Cell Lines as Neuronal and Microglia Model in Neurobiological Research

2021 ◽  
Vol 11 (9) ◽  
pp. 3729
Author(s):  
Katarzyna Balon ◽  
Benita Wiatrak
Keyword(s):  
Cell Culture ◽  
Dna Damage ◽  
Cell Lines ◽  
Inflammatory Factor ◽  
Research Model ◽  
Differentiated Cells ◽  
Undifferentiated Cells ◽  
Primary Cell Lines ◽  
Neurobiological Research ◽  
The Impact

Models based on cell cultures have become a useful tool in modern scientific research. Since primary cell lines are difficult to obtain and handle, neoplasm-derived lines like PC12 and THP-1 offer a cheap and flexible solution for neurobiological studies but require prior differentiation to serve as a neuronal or microglia model. PC12 cells constitute a suitable research model only after differentiation by incubation with nerve growth factor (NGF) and THP-1 cells after administering a differentiation factor such as phorbol 12-myristate-13-acetate (PMA). Still, quite often, studies are performed on these cancer cells without differentiation. The study aimed to assess the impact of PC12 or THP-1 cell differentiation on sensitivity to harmful factors such as Aβ25-35 (0.001–5 µM) (considered as one of the major detrimental factors in the pathophysiology of Alzheimer’s disease) or lipopolysaccharide (1–100 µM) (LPS; a pro-inflammatory factor of bacterial origin). Results showed that in most of the tests performed, the response of PC12 and THP-1 cells induced to differentiation varied significantly from the effect in undifferentiated cells. In general, differentiated cells showed greater sensitivity to harmful factors in terms of metabolic activity and DNA damage, while in the case of the free radicals, the results were heterogeneous. Obtained data emphasize the importance of proper differentiation of cell lines of neoplastic origin in neurobiological research and standardization of cell culture handling protocols to ensure reliable results.

scholarly journals Distinct p63 and p73 Protein Interactions Predict Specific Functions in mRNA Splicing and Polyploidy Control in Epithelia

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 25
Author(s):  
Julian M. Rozenberg ◽  
Olga S. Rogovaya ◽  
Gerry Melino ◽  
Nickolai A. Barlev ◽  
Alexander Kagansky
Keyword(s):  
Protein Interactions ◽  
Transcriptional Repression ◽  
Genome Stability ◽  
Spindle Assembly Checkpoint ◽  
Genotoxic Stress ◽  
Protein Protein Interactions ◽  
Proliferating Cells ◽  
P53 Family ◽  
Differentiated Cells ◽  
Specific Localization

Epithelial organs are the first barrier against microorganisms and genotoxic stress, in which the p53 family members p63 and p73 have both overlapping and distinct functions. Intriguingly, p73 displays a very specific localization to basal epithelial cells in human tissues, while p63 is expressed in both basal and differentiated cells. Here, we analyse systematically the literature describing p63 and p73 protein–protein interactions to reveal distinct functions underlying the aforementioned distribution. We have found that p73 and p63 cooperate in the genome stability surveillance in proliferating cells; p73 specific interactors contribute to the transcriptional repression, anaphase promoting complex and spindle assembly checkpoint, whereas p63 specific interactors play roles in the regulation of mRNA processing and splicing in both proliferating and differentiated cells. Our analysis reveals the diversification of the RNA and DNA specific functions within the p53 family.

scholarly journals BRG1 Controls the Activity of the Retinoblastoma Protein via Regulation of p21CIP1/WAF1/SDI

2004 ◽  
Vol 24 (3) ◽  
pp. 1188-1199 ◽  
Author(s):  
Hyeog Kang ◽  
Kairong Cui ◽  
Keji Zhao
Keyword(s):  
Transcriptional Repression ◽  
Cell Cycle Progression ◽  
Target Genes ◽  
Cellular Proliferation ◽  
Growth Arrest ◽  
Retinoblastoma Protein ◽  
Direct Interaction ◽  
Physical Interaction ◽  
Cdk Inhibitor ◽  
Regulation Of Cell Cycle

ABSTRACT The ubiquitous mammalian chromatin-remodeling SWI/SNF-like BAF complexes play critical roles in tumorigenesis. It was suggested that the direct interaction of BRG1 with the retinoblastoma protein pRB is required for regulation of cell cycle progression by pRB. We present evidence that the BRG1-containing complexes regulate the expression of the cdk inhibitor p21CIP1/WAF1/SDI. Furthermore, we show that the physical interaction between BRG1 and pRB is not required for induction of cell growth arrest and transcriptional repression of E2F target genes by pRB. Instead, BRG1 activates pRB by inducing its hypophosphorylation through up-regulation of the cdk inhibitor p21. The hypophosphorylation of pRB is reinforced by down-regulation of critical components, including cdk2, cyclin E, and cyclin D, in the pRB regulatory network. We demonstrate that up-regulation of p21 by BRG1 is necessary to induce formation of flat cells, growth arrest, and finally, cell senescence. Our results suggest that the BRG1-containing complexes control cellular proliferation and senescence by modulating the pRB pathway via multiple mechanisms.

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