Abstract
Elk1 belongs to the ternary complex (TCF) subfamily of the ETS-domain transcription factors. Several studies have implicated an important function for Elk1 in the CNS including synaptic plasticity and cell differentiation. Whilst studying ELK1 gene expression in rat brain a 54 aa N-terminally truncated isoform lacking the DBD was observed on immunoblots. A similar protein was also detected in NGF differentiated PC12 cells. It was proposed that this protein, referred to as sElk1, arose due to a de-novo initiation event at the second AUG codon on the Elk1 ORF. Transient over-expression of sElk1 potentiated neurite growth in the PC12 model and induced differentiation in the absence of NGF, leading to the proposition that it may have a specific function in the CNS. Here we report on the translational expression from the mouse and rat transcript and compare it with our earlier published work on human. Results demonstrate that the previously observed sElk1 protein is a non-specific band arising from the antibody employed. The tight conservation of the internal AUG reported to drive sElk1 expression is in fact coupled to Elk1 protein function, a result consistent with the Elk1-SRE crystal structure. It is also supported by the observed conservation of this methionine in the DBD of all ETS transcription factors independent of the N- or C-terminal positioning of this domain. Reporter assays demonstrate that elements both within the 5′UTR and downstream of the AUGElk1 serve to limit 40S access to the AUGsElk1 codon.
Highlights
Elk1 belongs to the ternary complex (TCF) subfamily of the ETS-domain transcription factors
Using the same antibody we observed a band in the PC12 model that co-migrated with a transiently expressed cDNA marker for sElk1, and noted that its expression was triggered by neuronal growth factor (NGF) treatment independent of the serum conditions (Figure 1A)
These cells have very high endogenous P-eIF2a levels compared to HEK293T cells and it seemed reasonable to assume, based upon our published model from the human gene, that this could explain the delayed reinitiation event required for ribosomal access to the AUGsElk1 [8]
Summary
Elk belongs to the ternary complex (TCF) subfamily of the ETS-domain transcription factors. The TCFs are major nuclear targets for MAPKs (mitogen-activated protein kinases) of the extracellular-signal regulated kinase (ERK) subfamily, and the closely related SAPK/JNK and p38MAPK stress-activated protein kinases They appear to act as an integration point for both growth and stress signals [1]. ERKs are abundant in this tissue and play important roles in neuronal survival, synaptic plasticity, long-term behavioural changes and memory learning These functions seem to be associated with IEG induction (in particular c-fos), and this in-turn suggests a central role for Elk in these processes [2,3,4,5]. It was proposed that it was generated by a de-novo initiation event at the second AUG in the Elk open reading frame (ORF) This 45 kDa protein was expressed uniquely in brain tissue and in nerve growth factor (NGF) differentiated PC12 cells. It was proposed that both Elk and sElk exercise important functions in the brain possibly coupled to the regulation of neurone differentiation
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