Phosphorylation of the Brn-3a transcription factor is modulated during differentiation and regulates its functional activity

Brn-3a is a transcription factor expressed in a subset of neurons of the peripheral nervous system. Its role encompasses the activation of genes involved in neuronal differentiation and survival. While a lot of data have been produced on Brn-3a target promoters, very little is known about the upstream regulatory signals that mediate its activation in response to differentiation. In this work, we describe for the first time that Brn-3a is phosphorylated in IMR-32 neuroblastoma cells in response to differentiation induced by retinoic acid treatment and that its post-translational modification is potentially mediated by the activation of the MAPK/ERK pathway. Furthermore, we show that the mutation of a putative phosphorylated amino acid strongly reduces the ability of Brn-3a to mediate the differentiation of IMR-32 cells.