The role of E2F1-topoIIβ signaling in regulation of cell cycle exit and neuronal differentiation of human SH-SY5Y cells.

This study aims to test the role of E2F1-topoIIβ signaling in neuronal differentiation of SH-SY5Y cells. With retinoic acid (RA) induction, a high percentage of cells were found to be arrested at the G/G phase, with decreased levels of cyclinD1, CDK4, phosphorylation status of pRb and E2F1, in addition to an elevated level of p27. The cells were shown to differentiate into neuronal phenotypes characterized by highly expressed neuronal markers, MAP2 and enriched topoIIβ, and remarkable neurite outgrowth. Exogenously forced E2F1 expression with a specific E2F1 plasmid led to suppression of topoIIβ expression and disruption of the neuronal differentiation of SH-SY5Y cells. On further examination using the ChIP assay, we found that E2F1 bound directly to the promoter region of topoIIβ, and its binding ability was inversely correlated with topoIIβ expression in response to RA induction. Thus, our findings suggest that E2F1-topoIIβ signaling may play a role in regulation of cell cycle exit and neuronal differentiation.