BIROn - Birkbeck Institutional Research Online

Regulation Of Brn-3a N-terminal transcriptional activity by MEK1/2-ERK1/2 signalling in neural differentiation

Berwick, D.C. and Calissano, M. and Corness, J.D. and Cook, S.J. and Latchman, David S. (2009) Regulation Of Brn-3a N-terminal transcriptional activity by MEK1/2-ERK1/2 signalling in neural differentiation. Brain Research 1256 , pp. 8-18. ISSN 0006-8993.

Full text not available from this repository.
Official URL: http://dx.doi.org/10.1016/j.brainres.2008.12.009

Abstract

The POU family transcription factor Brn-3a is required for the differentiation and survival of sensory neurones, and is phosphorylated in neuroblastoma cells following treatment with all-trans retinoic acid (RA). Mutation of serines-121 and -122 of Brn-3a to alanine blocks its phosphorylation and impairs RA-mediated neurite outgrowth. Here we show that this deficit in differentiation is mimicked by a single mutation at serine-122, and demonstrate a similar requirement for a second residue, threonine-39. Like Brn-3a, the neuropeptide Galanin has been implicated in the development of sensory neurones. We show that Brn-3a over-expression acts synergistically with RA treatment to up-regulate Galanin promoter activity; that the activity of the N-terminal transcriptional activation domain of Brn-3a is increased following RA treatment; and that both these effects require threonine-39 and serine-122. In addition, we demonstrate that the RA-mediated activation of Galanin promoter activity and Brn-3a N-terminal transcriptional activity are both blocked by pan-MEK inhibitors, and show that the expression of a constitutively-active mutant of MEK1, but not MEK5, is sufficient to increase Brn-3a activity. These results reveal an important role for the ERK1/2 pathway in Brn-3a regulation during RA-mediated neuronal differentiation and define the neuropeptide Galanin as a novel target of this transcription factor.

Item Type: Article
Keyword(s) / Subject(s): Brn-3a, Galanin, ERK1/2, neural differentiation, retinoic acid
School or Research Centre: Central Administration Departments > Master's Office
Depositing User: Administrator
Date Deposited: 28 Jul 2011 10:08
Last Modified: 17 Apr 2013 12:21
URI: http://eprints.bbk.ac.uk/id/eprint/3900

Archive Staff Only (login required)

Edit/View Item Edit/View Item