| http://purl.uniprot.org/citations/18566606 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18566606 | http://www.w3.org/2000/01/rdf-schema#comment | "Studies of the cell death pathway in the nematode Caenorhabditis elegans provided the first evidence of the evolutionary conservation of apoptosis signalling. Here we show that the worm Bcl-2 homology domain-3 (BH3)-only protein EGL-1 binds mammalian pro-survival proteins very poorly, but can be converted into a high-affinity ligand for Bcl-2 and Bcl-x(L) by subtle mutation of the cysteine residue at position 62 within the BH3 domain. A 100-fold increase in affinity was observed following a single atom change (cysteine to serine substitution), and a further 10-fold increase by replacement with glycine. The low affinity of wild-type EGL-1 for mammalian pro-survival proteins and its poor expression correlates with its weak killing activity in mammalian cells whereas the high-affinity C62G mutant is a very potent killer of cells lacking Mcl-1. Cell killing by the C62S mutant with intermediate affinity only occurs when this EGL-1 BH3 domain is placed in a more stable context, namely that of Bim(S), which allows higher expression, though the kinetics of cell death now vary depending on whether Mcl-1 is neutralized by Noxa or genetically deleted. These results demonstrate how levels of BH3-only proteins, target affinity and the spectrum of neutralization of pro-survival proteins all contribute to killing activity."xsd:string |
| http://purl.uniprot.org/citations/18566606 | http://purl.org/dc/terms/identifier | "doi:10.1038/cdd.2008.86"xsd:string |
| http://purl.uniprot.org/citations/18566606 | http://purl.uniprot.org/core/author | "Chen L."xsd:string |
| http://purl.uniprot.org/citations/18566606 | http://purl.uniprot.org/core/author | "Yang H."xsd:string |
| http://purl.uniprot.org/citations/18566606 | http://purl.uniprot.org/core/author | "Huang D.C."xsd:string |
| http://purl.uniprot.org/citations/18566606 | http://purl.uniprot.org/core/author | "Colman P.M."xsd:string |
| http://purl.uniprot.org/citations/18566606 | http://purl.uniprot.org/core/author | "Fairlie W.D."xsd:string |
| http://purl.uniprot.org/citations/18566606 | http://purl.uniprot.org/core/author | "Lee E.F."xsd:string |
| http://purl.uniprot.org/citations/18566606 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18566606 | http://purl.uniprot.org/core/name | "Cell Death Differ"xsd:string |
| http://purl.uniprot.org/citations/18566606 | http://purl.uniprot.org/core/pages | "1609-1618"xsd:string |
| http://purl.uniprot.org/citations/18566606 | http://purl.uniprot.org/core/title | "EGL-1 BH3 mutants reveal the importance of protein levels and target affinity for cell-killing potency."xsd:string |
| http://purl.uniprot.org/citations/18566606 | http://purl.uniprot.org/core/volume | "15"xsd:string |
| http://purl.uniprot.org/citations/18566606 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/18566606 |
| http://purl.uniprot.org/citations/18566606 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/18566606 |
| http://purl.uniprot.org/uniprot/#_A0A1L4AQQ4-mappedCitation-18566606 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18566606 |
| http://purl.uniprot.org/uniprot/#_P10415-mappedCitation-18566606 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18566606 |
| http://purl.uniprot.org/uniprot/#_Q07817-mappedCitation-18566606 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18566606 |
| http://purl.uniprot.org/uniprot/#_A0A0S2Z3C5-mappedCitation-18566606 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18566606 |
| http://purl.uniprot.org/uniprot/#_A0A0S2Z3D2-mappedCitation-18566606 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18566606 |
| http://purl.uniprot.org/uniprot/#_A0A1L4AQQ5-mappedCitation-18566606 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18566606 |
| http://purl.uniprot.org/uniprot/#_A0A1L4AQQ8-mappedCitation-18566606 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18566606 |
| http://purl.uniprot.org/uniprot/#_A0A1L4AQR6-mappedCitation-18566606 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18566606 |
| http://purl.uniprot.org/uniprot/#_A0A7I2V3S7-mappedCitation-18566606 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18566606 |