An AUG Codon Conserved for Protein Function Rather than Translational Initiation: The Story of the Protein sElk1
| Autor: | Odin Kuijpers, Béatrice Conne, Joseph Curran, Pascale Jaquier-Gubler, Tanguy Araud, Noémie Legrand |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Cellular differentiation
lcsh:Medicine Gene Expression PC12 Cells Biochemistry 0302 clinical medicine Start codon ddc:590 Antibody Specificity Gene expression ddc:576.5 lcsh:Science Peptide Chain Initiation Translational Genetics ddc:616 0303 health sciences Multidisciplinary Immune System Proteins Cell Differentiation Cell biology DNA-Binding Proteins Transcription Activators Research Article Gene isoform Molecular Sequence Data Biology DNA-binding protein Antibodies Cell Line Molecular Genetics 03 medical and health sciences ELK1 Cell Line Tumor Animals Humans Amino Acid Sequence Codon Transcription factor Molecular Biology 030304 developmental biology ets-Domain Protein Elk-1 Translation Initiation Base Sequence lcsh:R HEK 293 cells Biology and Life Sciences Proteins Rats HEK293 Cells lcsh:Q Protein Translation Sequence Alignment 030217 neurology & neurosurgery Transcription Factors |
| Zdroj: | PLOS ONE, Vol. 9, No 7 (2014) P. e102890 PLoS ONE PLoS ONE, Vol 9, Iss 7, p e102890 (2014) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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