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vel ligand that modulates the protein – protein interactions of the AAA + superfamily oncoprotein reptin †
| Content Provider | Semantic Scholar |
|---|---|
| Author | Healy, Alan R. Houston, Douglas R. Remnant, Lucy Huart, Anne-Sophie Brychtová, Veronika Maslon, Magda M. Meers, Olivia Muller, Petr Krejčí, Adam Blackburn, Elizabeth A. Vojtesek, Borivoj Hernychová, Lenka Walkinshaw, Malcolm D. Westwood, Nicholas James Hupp, Ted R. |
| Copyright Year | 2015 |
| Abstract | Developing approaches to discover protein–protein interactions (PPIs) remains a fundamental challenge. A chemical biology platform is applied here to identify novel PPIs for the AAA+ superfamily oncoprotein reptin. An in silico screen coupled with chemical optimization provided Liddean, a nucleotide-mimetic which modulates reptin's oligomerization status, protein-binding activity and global conformation. Combinatorial peptide phage library screening of Liddean-bound reptin with next generation sequencing identified interaction motifs including a novel reptin docking site on the p53 tumor suppressor protein. Proximity ligation assays demonstrated that endogenous reptin forms a predominantly cytoplasmic complex with its paralog pontin in cancer cells and Liddean promotes a shift of this complex to the nucleus. An emerging view of PPIs in higher eukaryotes is that they occur through a striking diversity of linear peptide motifs. The discovery of a compound that alters reptin's protein interaction landscape potentially leads to novel avenues for therapeutic development. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://pubs.rsc.org/en/Content/ArticlePDF/2015/SC/C4SC03885A |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
