Transcription factor AP2alpha (TFAP2a) regulates differentiation and proliferation of neuroblastoma cells

2008 ◽  
Vol 271 (1) ◽  
pp. 56-63 ◽  
Author(s):  
Johannes H. Schulte ◽  
Jutta Kirfel ◽  
Soyoung Lim ◽  
Alexander Schramm ◽  
Nicolaus Friedrichs ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Neuroblastoma Cells ◽  
Differentiation And Proliferation

Transcription factor AP2alpha (TFAP2a) regulates differentiation and proliferation of neuroblastoma cells

2009 ◽  
Vol 221 (03) ◽  
Author(s):  
F Pentek ◽  
J Kirfel ◽  
S Lim ◽  
A Schramm ◽  
N Friedrichs ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Neuroblastoma Cells ◽  
Differentiation And Proliferation

The transcription factor activating protein 2 beta (TFAP2B) mediates neuronal differentiation in neuroblastoma cells

2013 ◽  
Vol 225 (03) ◽  
Author(s):  
F Sherkheli ◽  
S Ackermann ◽  
F Roels ◽  
H Kocak ◽  
R Volland ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Neuronal Differentiation ◽  
Neuroblastoma Cells

scholarly journals Transcriptomic profile of Pea3 family members reveal regulatory codes for axon outgrowth and neuronal connection specificity

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Başak Kandemir ◽  
Gizem Gulfidan ◽  
Kazim Yalcin Arga ◽  
Bayram Yilmaz ◽  
Isil Aksan Kurnaz
Keyword(s):  
Transcription Factor ◽  
Target Genes ◽  
Neural Circuit ◽  
Molecular Model ◽  
Expression Profiles ◽  
Neuroblastoma Cells ◽  
Branching Morphogenesis ◽  
Subfamily Member ◽  
Circuit Formation ◽  
Cell Cell

Abstract PEA3 transcription factor subfamily is present in a variety of tissues with branching morphogenesis, and play a particularly significant role in neural circuit formation and specificity. Many target genes in axon guidance and cell–cell adhesion pathways have been identified for Pea3 transcription factor (but not for Erm or Er81); however it was not so far clear whether all Pea3 subfamily members regulate same target genes, or whether there are unique targets for each subfamily member that help explain the exclusivity and specificity of these proteins in neuronal circuit formation. In this study, using transcriptomics and qPCR analyses in SH-SY5Y neuroblastoma cells, hypothalamic and hippocampal cell line, we have identified cell type-specific and subfamily member-specific targets for PEA3 transcription factor subfamily. While Pea3 upregulates transcription of Sema3D and represses Sema5B, for example, Erm and Er81 upregulate Sema5A and Er81 regulates Unc5C and Sema4G while repressing EFNB3 in SH-SY5Y neuroblastoma cells. We furthermore present a molecular model of how unique sites within the ETS domain of each family member can help recognize specific target motifs. Such cell-context and member-specific combinatorial expression profiles help identify cell–cell and cell-extracellular matrix communication networks and how they establish specific connections.

scholarly journals The tumour suppressor p53 regulates the expression of amyloid precursor protein (APP)

2009 ◽  
Vol 418 (3) ◽  
pp. 643-650 ◽  
Author(s):  
Ascensión Cuesta ◽  
Alberto Zambrano ◽  
María Royo ◽  
Angel Pascual
Keyword(s):  
Transcription Factor ◽  
Amyloid Precursor Protein ◽  
Dna Sequences ◽  
Primary Cultures ◽  
Neuroblastoma Cells ◽  
Dominant Negative ◽  
Precursor Protein ◽  
Human Neuroblastoma Cell ◽  
Dependent Manner ◽  
Human Neuroblastoma

The expression of the APP (amyloid precursor protein), which plays a key role in the development of AD (Alzheimer's disease), is regulated by a variety of cellular mediators in a cell-dependent manner. In this study, we present evidence that p53 regulates the expression of the APP gene in neuroblastoma cells. Transient expression of ectopic p53, activation of endogenous p53 by the DNA-damaging drug camptothecin or Mdm2 (murine double minute 2) depletion decreases the intracellular levels of APP in murine N2aβ neuroblastoma cells. This effect was also observed in primary cultures of rat neurons as well as in SH-SY5Y cells, a human neuroblastoma cell line. Transient transfection studies using plasmids that contain progressive deletions of the 5′ region of the gene demonstrate that p53 represses APP promoter activity through a mechanism that is mediated by DNA sequences located downstream of the transcription start site (+55/+101). Accordingly, expression of a dominant-negative p53 mutant significantly increases the transcriptional activity of the APP promoter. In addition, results obtained in gel mobility-shift assays show that p53 does not bind to the +55/+101 APP region, although it reduces binding of the transcription factor Sp1 (stimulating protein 1). Reduction of Sp1 binding after activation of p53 with camptothecin was also observed in chromatin immunoprecipitation assays. Altogether, our results strongly suggest a mechanism by which p53 precludes binding of Sp1 to DNA, and therefore the stimulation of the APP promoter by this transcription factor.

scholarly journals The PERK-EIF2α-ATF4 signaling branch regulates osteoblast differentiation and proliferation by PTH

2019 ◽  
Vol 316 (4) ◽  
pp. E590-E604 ◽  
Author(s):  
Kefan Zhang ◽  
Miaomiao Wang ◽  
Yingjiang Li ◽  
Chunping Li ◽  
Shaidi Tang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endoplasmic Reticulum ◽  
Transcription Factor ◽  
Er Stress ◽  
Signaling Pathway ◽  
Osteoblast Differentiation ◽  
Type I ◽  
Matrix Mineralization ◽  
Related Peptide ◽  
Differentiation And Proliferation

Parathyroid hormone (PTH) and its related peptide (PTH-related peptide 1–34) are two of the Food and Drug Administration-approved bone-promoting drugs for age-related osteoporosis. Treatment with PTH stimulates bone formation. However, the molecular mechanisms of PTH-mediated osteoblast differentiation and cell proliferation are still not completely understood. In this study, we showed that PTH induced endoplasmic reticulum (ER) stress in osteoblasts through the PKR-like endoplasmic reticulum kinase (PERK)-eukaryotic initiation factor 2α (EIF2α)-activating transcription factor 4 (ATF4)-signaling pathway. After separately blocking PERK-EIF2α-ATF4 signaling with two different inhibitors [AMG’44 and integrated stress response inhibitor (ISRIB)] or specific small interfering RNA for PERK and ATF4, the following targets were all downregulated: expression of osteoblast differentiation markers [runt-related transcription factor 2 (Runx2), alkaline phosphatase (Alp), type I collagen (Col1a1), and osteocalcin (Ocn)], cell proliferation markers (CyclinE, CyclinD, and CDC2), amino acid import (Glyt1), and metabolism-related genes (Asns). Additionally, Alp-positive staining cells, Alp activity, matrix mineralization, Ocn secretion, and cell proliferation indexes were inhibited. Interestingly, we found that salubrinal enhanced PTH-induced osteoblast differentiation and proliferation by maintenance of phosphorylation of EIF2α. Furthermore, we observed that PTH increased the association between heat shock protein 90 (HSP90) and PERK and maintained PERK protein stabilization in the early stages of PTH-induced ER stress. Treatment of MC3T3-E1 cells with geldanamycin, an HSP90 inhibitor, decreased PERK protein expression and inhibited osteoblast differentiation and cell proliferation upon PTH treatment. Taken together, our data demonstrate that PTH regulates osteoblast differentiation and cell proliferation, partly by activating the HSP90-dependent PERK-EIF2α-ATF4 signaling pathway.

scholarly journals ER stress signaling has an activating transcription factor 6α (ATF6)-dependent “off-switch”

2018 ◽  
Vol 293 (47) ◽  
pp. 18270-18284 ◽  
Author(s):  
Franziska Walter ◽  
Aisling O'Brien ◽  
Caoimhín G. Concannon ◽  
Heiko Düssmann ◽  
Jochen H. M. Prehn
Keyword(s):  
Transcription Factor ◽  
Er Stress ◽  
Neuroblastoma Cells ◽  
Stress Signaling ◽  
Signaling Proteins ◽  
Protein Levels ◽  
Activating Transcription Factor ◽  
Screening Platform ◽  
The Unfolded Protein Response ◽  
Activating Transcription Factor 6Α

In response to an accumulation of unfolded proteins in the endoplasmic reticulum (ER) lumen, three ER transmembrane signaling proteins, inositol-requiring enzyme 1 (IRE1), PRKR-like ER kinase (PERK), and activating transcription factor 6α (ATF6α), are activated. These proteins initiate a signaling and transcriptional network termed the unfolded protein response (UPR), which re-establishes cellular proteostasis. When this restoration fails, however, cells undergo apoptosis. To investigate cross-talk between these different UPR enzymes, here we developed a high-content live cell screening platform to image fluorescent UPR-reporter cell lines derived from human SH-SY5Y neuroblastoma cells in which different ER stress signaling proteins were silenced through lentivirus-delivered shRNA constructs. We observed that loss of ATF6 expression results in uncontrolled IRE1-reporter activity and increases X box–binding protein 1 (XBP1) splicing. Transient increases in both IRE1 mRNA and IRE1 protein levels were observed in response to ER stress, suggesting that IRE1 up-regulation is a general feature of ER stress signaling and was further increased in cells lacking ATF6 expression. Moreover, overexpression of the transcriptionally active N-terminal domain of ATF6 reversed the increases in IRE1 levels. Furthermore, inhibition of IRE1 kinase activity or of downstream JNK activity prevented an increase in IRE1 levels during ER stress, suggesting that IRE1 transcription is regulated through a positive feed-forward loop. Collectively, our results indicate that from the moment of activation, IRE1 signaling during ER stress has an ATF6-dependent “off-switch.”

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