Wildtype Elk-1, but not a SUMOylation mutant, represses egr-1 expression in SH-SY5Y neuroblastomas.

Elk-1, an ETS domain transcription factor of the TCF (ternary complex factor) subfamily, is known to be involved in the regulation of immediate-early genes such as c-fos upon mitogen activation, and thus commonly implied in cell proliferation. Early growth response-1, Egr-1, which was known to be an immediate-early gene, has recently been shown to be pro-apoptotic for SH-SY5Y neuroblastoma cells. In that respect, it was not clear whether Elk-1 would activate or repress from this promoter, since Elk-1 is mostly associated with proliferation and not apoptosis. In this study, we wanted to address whether Elk-1 activates or represses egr-1 promoter in neuroblastoma cells, and using a combination of RNA interference and reporter analyses, we present evidence that egr-1 gene is repressed by Elk-1 in normally cycling SH-SY5Y neuroblastoma cell line in a SUMO (small ubiquitin-related modifier)-dependent manner, a potential mechanism used by these cells to bypass apoptosis.