Elk-1 a transcription factor with multiple facets in the brain
- Laboratoire de Physiopathologie des Maladies du Système Nerveux Central, UMR CNRS-7224 CNRS et UMRS-INSERM 952, Université Pierre et Marie Curie-Paris 6, Paris, France
The ternary complex factor (TCF) Elk-1 is a transcription factor that regulates immediate early gene (IEG) expression via the serum response element (SRE) DNA consensus site. Elk-1 is associated with a dimer of serum response factor (SRF) at the SRE site, and its phosphorylation occurs at specific residues in response to mitogen-activated protein kinases (MAPKs), including c-Jun-N terminal kinase (JNK), p38/MAPK, and extracellular-signal regulated kinase (ERK). This phosphorylation event is critical for triggering SRE-dependent transcription. Although MAPKs are fundamental actors for the instatement and maintenance of memory, and much investigation of their downstream signaling partners have been conducted, no data yet clearly implicate Elk-1 in these processes. This is partly due to the complexity of Elk-1 sub-cellular localization, and hence functions, within neurons. Elk-1 is present in its resting state in the cytoplasm, where it colocalizes with mitochondrial proteins or microtubules. In this particular sub-cellular compartment, overexpression of Elk-1 is toxic for neuronal cells. When phosphorylated by the MAPK/ERK, Elk-1 translocates to the nucleus where it is implicated in regulating chromatin remodeling, SRE-dependent transcription, and neuronal differentiation. Another post-translational modification is the conjugation to SUMO (Small Ubiquitin-like MOdifier), which relocalizes Elk-1 in the cytoplasm. Thus, Elk-1 plays a dual role in neuronal functions: pro-apoptotic within the cytoplasm, and pro-differentiation within the nucleus. To address the role of Elk-1 in the brain, one must be aware of its multiple facets, and design molecular tools that will shut down Elk-1 expression, trafficking, or activation, in specific neuronal compartments. We summarize in this review the known molecular functions of Elk-1, its regulation in neuronal cells, and present evidence of its possible implication in model systems of synaptic plasticity, learning, but also in neurodegenerative diseases.
Keywords: ERK signaling, gene regulation, chromatin remodeling, brain plasticity, memory formation, long-term neuronal adaptation
Citation: Besnard A, Galan-Rodriguez B, Vanhoutte P and Caboche J (2011) Elk-1 a transcription factor with multiple facets in the brain. Front. Neurosci. 5:35. doi: 10.3389/fnins.2011.00035
Received: 30 December 2010;
Paper pending published: 22 January 2011;
Accepted: 04 March 2011; Published online: 16 March 2011.
Edited by:Shannon K. Mcweeney, Oregon Clinical and Translational Research Institute, USA
Reviewed by:Claudio V. Mello, Oregon Health and Science University, USA
Hans P. Herzel, Humboldt University, Germany
Copyright: © 2011 Besnard, Galan-Rodriguez, Vanhoutte and Caboche. This is an open-access article subject to an exclusive license agreement between the authors and Frontiers Media SA, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.
*Correspondence: Jocelyne Caboche and Peter Vanhoutte, Laboratoire de Physiopathologie des Maladies du Système Nerveux Central, UMR CNRS-7224 CNRS et UMRS-INSERM 952, Université Pierre et Marie Curie-Paris 6, Paris, France. e-mail: firstname.lastname@example.org; email@example.com