Regulacion de la actividad transcripcional del gen crmp2 en celulas de neuroblastoma estudio de su posible implicacion en la diferenciacion axonal

Abstract

The family of the collapsin response mediator proteins (crmp) has been implicated in a great number of processes involved in cytoskeleton control. These proteins are related to tissue morphogenesis, cellular mi gration and axonal pathfinding. crmps present high expression íevel in the embryo while it diminisnes in the adult, in fact, some proteins from this family have been shown to play a role in tumour transformation.%&/This work has been focussed on the study of transcriptional regulation of CRMP-2 gene, we started studying basa! regulation of this gene transen'ption. We infered from this study that AP-2 and PAX-3 transcription factors play an important role in the transcriptional modulation of CRMP-2 gene in SH-SY5Y neuroblastoma cells. Subsequently, we have studied CRMP-2 gene regulation in response to all-trans reti noic acid (atra) treatment in SH-SY5Y cells. atra promotes the differentiation of these cells, triggering the development of the axon. atra treatment causes a decrease in AP-2 and Pax-3 binding to their respective consensus sites in CRMP-2 promoter. Pax-3 binding activity regulation seems to be performed at the transcriptional level but AP-2 binding to CRMP-2 promoter seems to oceur through a different mechanism that do not implícate the interaction with the retinoblastoma protein. We have also performed some studies devoted to clarify CRMP-2 protein expression levéis, phospnorylation status and subcellular localization in control and atra treated SH-SY5Y neuroblastoma cells. /Unravelling the molecular mechanisms behind the action of atra on neuroblastoma cells could offer new perspectives in its clinical applications.