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• W2029890603 abstract "<i>Lot1</i>, a zinc finger transcription factor acting as a tumor suppressor gene on tumoral cells, is highly expressed during brain development. In developing rat cerebellum, <i>Lot1</i> expression is high in cerebellar granule cells (CGC), a neuronal population undergoing postnatal neurogenesis. The time course of <i>Lot1</i> cerebellar expression closely matches the expression of pituitary adenylate cyclase-activating polypeptide (PACAP) receptors coupled to adenylyl cyclase. The aim of this study was to ascertain whether <i>Lot1</i> expression is regulated by cAMP-dependent pathways and to identify mechanisms of <i>Lot1</i> activation in CGC cultures. Our results show that <i>Lot1</i> expression in CGC is cAMP-dependent, as treatments with either forskolin or PACAP-38 induced an increase in its expression at both the mRNA and protein levels. This effect on <i>Lot1</i> expression was mimicked by dibutyryl cAMP and suppressed by protein kinase A and MEK inhibitors. In parallel, we found that treatments with forskolin and PACAP-38 in precursor CGC inhibited bromodeoxyuridine incorporation by 25 and 35%, respectively, indicating a negative effect on neuronal precursor proliferation. Luciferase reporter analysis and mutagenesis of the <i>Lot1</i> promoter region indicated a crucial role of the AP1-binding site (located at -268 bp) in cAMP-induced <i>Lot1</i> transcription. In addition, cotransfection experiments indicated that the c-Fos/c-Jun heterodimer is responsible for cAMP-dependent <i>Lot1</i> transcriptional activation. In conclusion, our data demonstrate that, in CGC, <i>Lot1</i> is under the transcriptional control of cAMP through an AP1 site regulated by the c-Fos/c-Jun heterodimer and suggest that this gene may be an important element of the cAMP-mediated pathway that regulates neuronal proliferation through the protein kinase A-MEK signaling cascade." @default.
• W2029890603 created "2016-06-24" @default.
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• W2029890603 date "2005-09-01" @default.
• W2029890603 modified "2023-09-29" @default.
• W2029890603 title "Cyclic AMP-mediated Regulation of Transcription Factor Lot1 Expression in Cerebellar Granule Cells" @default.
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• W2029890603 doi "https://doi.org/10.1074/jbc.m413323200" @default.
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