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dc.contributor.authorLópez-Carballo, Gracia-
dc.contributor.authorMoreno, Lucrecia-
dc.contributor.authorMasiá, Susana-
dc.contributor.authorPérez, Paloma-
dc.contributor.authorBarettino, Domingo-
dc.identifier.citationJ Biol Chem. 2002 Jul 12;277(28):25297-304en_US
dc.description8 pages, 6 figures.--PMID: 12000752 [PubMed]en_US
dc.description.abstractRetinoic acid (RA) induces neural differentiation of SH-SY5Y neuroblastoma cells. We show that the mRNA levels of the differentiation-inhibiting basic helix-loop-helix transcription factors ID1, ID2, and ID3 are down-regulated during RA-induced differentiation of SH-SY5Y cells. The levels of ID proteins decreased in parallel to the observed transcriptional repression. The expression of other basic helix-loop-helix genes changed during RA-induced differentiation: expression of neuroblast-specific ASCL1 (HASH-1) gene was promptly reduced after RA treatment, whereas expression of differentiation-promoting genes NEUROD6 (NEX-1, HATH-2) and NEUROD1 was increased. Treatments with 12-O-tetradecanoylphorbol-13-acetate, another inducer of neuroblastoma cell differentiation, also resulted in coordinated down-regulation of ID gene expression, underscoring the role of ID genes in differentiation. Down-regulation of ID gene expression by RA involves a complex mechanism because full transcriptional repression required newly synthesized proteins and signaling by phosphatidylinositol 3-kinase (PI3K). RA treatment activates the PI3K/Akt signaling pathway, resulting in increased PI3K activity in extracts from RA-treated cells and a rapid increase in phosphorylation of Akt in Ser-473. Inhibition of PI3K by LY294002 impaired RA-induced differentiation, as assessed by morphological and biochemical criteria. We propose that RA, by activating the PI3K/Akt signaling pathway, plays an important role in the regulation of neuronal cell survival.en_US
dc.description.sponsorshipThis work has been supported by grants of the Spanish Ministry of Education and Culture (PM96-0073) and Ministry of Science and Technology (PM1999-0112) to D.B. G. L.-C. was the recipient of a pre-doctoral fellowship (FPI) from the Consellería de Educación y Cultura de la Generalitat Valenciana. L.M. was the recipient of a fellowship from the Bancaixa-CSIC Program. S. M. was the recipient of a pre-doctoral fellowship (FPI) from the Ministry of Science and Technology.en_US
dc.format.extent578659 bytes-
dc.publisherAmerican Society for Biochemistry and Molecular Biologyen_US
dc.titleActivation of the phosphatidylinositol 3-kinase/Akt signaling pathway by retinoic acid is required for neural differentiation of SH-SY5Y human neuroblastoma cellsen_US
dc.description.peerreviewedPeer revieweden_US
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