tailieunhanh - Báo cáo khoa học: All-trans-retinoic acid inhibits collapsin response mediator protein-2 transcriptional activity during SH-SY5Y neuroblastoma cell differentiation

Neurons are highly polarized cells composed of two structurally and func-tionally 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 fre-quent in neuro-oncologic diseases. | ễFEBS Journal All-trans-retinoic acid inhibits collapsin response mediator protein-2 transcriptional activity during SH-SY5Y neuroblastoma cell differentiation Lorena Fontan-Gabas1 Erik Oliemuller2 Juan Jose Martinez-Irujo1 2 Carlos de Miguel1 and Ana Rouzaut1 2 1 Department of Biochemistry University of Navarra Pamplona Spain 2 Division of Oncology Center for Applied MedicalResearch University of Navarra Pamplona Spain Keywords CRMP-2 gene regulation neuroblastoma promoter retinoic acid Correspondence A. Rouzaut Center for Applied Medical Research University of Navarra Av. Pio XII 55 31008 Pamplona Spain Fax 34 948 19 47 18 Tel 34 948 19 47 00 E-mail arouzaut@ Received 14 July 2006 revised 9 October 2006 accepted 16 November 2006 doi 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 .