Title: Re‐evaluation of desmethyl, desamino‐PateamineA targeting of eukaryotic translation initiation factor 4F (975.2)
Abstract: The marine natural product PateamineA (PatA) and the simplified analog desmethyl, desamino PateamineA (DMDAPatA) have cytotoxicity selective for rapidly proliferating cells by inhibition of cap‐dependent translation initiation through binding to eIF4A (eukaryotic initiation factor 4A). eIF4A is a member of eIF4F which includes eIF4E (cap‐binding protein) and eIF4G (scaffolding protein). eIF4A is a DEAD‐box helicase that unwinds secondary structure in the 5ʹ‐untranslated region (5ʹ‐UTR) of mRNA allowing for recruitment of the 43S pre‐initiation complex containing the small ribosomal subunit. The small ribosomal subunit then “scans” the 5ʹ‐UTR in search of the AUG start codon which triggers translation. Previously we had proposed a model where binding by PatA/DMDAPatA to eIF4A disrupts the integrity of the eIF4F complex by directly perturbing the protein‐protein interactions between eIF4A and eIF4G causing an inhibition of eIF4A‐ and hence eIF4F‐dependent translation initiation. However, more detailed structural studies have suggested that the eIF4A‐eIF4G interaction is not directly disrupted by PatA. We have re‐examined the integrity of eIF4F complexes in the presence of DMDAPatA, and our preliminary results suggest the potential dependency of prior binding of eIF4E to eIF4G along with eIF4E cap‐binding for disruption of the eIF4A‐eIF4G interaction by DMDAPatA. Grant Funding Source : Supported by St. John's University
Publication Year: 2014
Publication Date: 2014-04-01
Language: en
Type: article
Indexed In: ['crossref']
Access and Citation
AI Researcher Chatbot
Get quick answers to your questions about the article from our AI researcher chatbot