Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The molecular basis of neuroendocrine-specific expression of chromogranin B gene (Chgb) has remained elusive. Utilizing wild-type and mutant Chgb promoter/luciferase reporter constructs, this study established a crucial role for the cAMP response element (CRE) box at -102/-95 bp in endocrine [rat pheochromocytoma (chromaffin) cell line (PC12) and rat pituitary somatotrope cell line (GC)] and neuronal [rat dorsal root ganglion/mouse neuroblastoma hybrid cell line (F-11), cortical and hippocampal primary neurons] cells. Additionally, G/C-rich domains at -134/-127, -125/-117 and -115/-110 bp played especially important roles for endocrine-specific expression of the Chgb gene. Co-transfection of expression plasmids for CREB, activator protein-2 (transcription factor) (AP-2), early growth response protein (transcription factor) (Egr-1) or specificity protein 1 (transcription factor) (Sp1) with the Chgb promoter constructs trans-activated expression of the Chgb gene. Nuclear extracts from either PC12 or F-11 cells formed specific complexes with the Chgb (-110/-87 bp) (CRE) oligonucleotide, which were either supershifted or disrupted by anti-CREB antibodies. In addition PC12 nuclear extracts also formed a specific complex with a Chgb (-140/-104-bp) oligonucleotide containing three G/C-rich regions, which was dose-dependently disrupted by anti-AP-2, anti-Egr-1 or anti-Sp1 antibodies; indeed, any one of these three antibodies completely abolished the complex, suggesting that all three factors bind the region simultaneously, at least in vitro. Chromatin immunoprecipitation assays documented the binding of the transcription factors CREB, AP-2, Egr-1 and Sp1 to the chromosomal Chgb gene promoter in vivo in PC12 cells within the context of chromatin. We conclude that the neuroendocrine-specific expression of Chgb is mediated by the CRE and G/C boxes in cis and the transcription factors CREB, AP-2, Egr-1 and Sp1 in trans.
 ...
PMID:Molecular basis of neuroendocrine cell type-specific expression of the chromogranin B gene: Crucial role of the transcription factors CREB, AP-2, Egr-1 and Sp1. 1698 40

Neurons are highly polarized cells composed of two structurally and functionally distinct parts, the axon and the dendrite. The establishment of this asymmetric structure is a tightly regulated process. In fact, alterations in the proteins involved in the configuration of the microtubule lattice are frequent in neuro-oncologic diseases. One of these cytoplasmic mediators is the protein known as collapsin response mediator protein-2, which interacts with and promotes tubulin polymerization. In this study, we investigated collapsin response mediator protein-2 transcriptional regulation during all-trans-retinoic acid-induced differentiation of SH-SY5Y neuroblastoma cells. All-trans-retinoic acid is considered to be a potential preventive and therapeutic agent, and has been extensively used to differentiate neuroblastoma cells in vitro. Therefore, we first demonstrated that collapsin response mediator protein-2 mRNA levels are downregulated during the differentiation process. After completion of deletion construct analysis and mutagenesis and mobility shift assays, we concluded that collapsin response mediator protein-2 basal promoter activity is regulated by the transcription factors AP-2 and Pax-3, whereas E2F, Sp1 and NeuroD1 seem not to participate in its regulation. Furthermore, we finally established that reduced expression of collapsin response mediator protein-2 after all-trans-retinoic acid exposure is associated with impaired Pax-3 and AP-2 binding to their consensus sequences in the collapsin response mediator protein-2 promoter. Decreased attachment of AP-2 is a consequence of its accumulation in the cytoplasm. On the other hand, Pax-3 shows lower binding due to all-trans-retinoic acid-mediated transcriptional repression. Unraveling the molecular mechanisms behind the action of all-trans-retinoic acid on neuroblastoma cells may well offer new perspectives for its clinical application.
 ...
PMID:All-trans-retinoic acid inhibits collapsin response mediator protein-2 transcriptional activity during SH-SY5Y neuroblastoma cell differentiation. 1722 53


<< Previous 1 2 3