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|All-trans-retinoic acid inhibits collapsin response mediator protein-2 transcriptional activity during SH-SY5Y neuroblastoma cell differentiation|
|Authors: ||Fontan, L. (Lorena)|
Oliemuller, E. (Erik)
Martinez-Irujo, J.J. (Juan José)
Miguel, C. (Carlos) de
Rouzaut, A. (Ana)
|Issue Date: ||2007|
|Publisher: ||Wiley Blackwell|
|Publisher version: ||http://onlinelibrary.wiley.com/doi/10.1111/j.1742-4658.2006.05597.x/abstract|
|Citation: ||Fontan-Gabas L, Oliemuller E, Martinez-Irujo JJ, de Miguel C, Rouzaut A. All-trans-retinoic acid inhibits collapsin response mediator protein-2 transcriptional activity during SH-SY5Y neuroblastoma cell differentiation. FEBS J 2007 Jan;274(2):498-511.|
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.
|Permanent link: ||http://hdl.handle.net/10171/20291|
|Appears in Collections:||DA - Ciencias - Bioquímica y Biología molecular - Artículos de Revista|
DA - CIMA - Oncología - Microambiente tumoral - Artículos de revista
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