| http://purl.uniprot.org/citations/32661419 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/32661419 | http://www.w3.org/2000/01/rdf-schema#comment | "Apoptosis is regulated by BCL-2 family proteins. Anti-apoptotic members suppress cell death by deploying a surface groove to capture the critical BH3 α-helix of pro-apoptotic members. Cancer cells hijack this mechanism by overexpressing anti-apoptotic BCL-2 family proteins to enforce cellular immortality. We previously identified and harnessed a unique cysteine (C55) in the groove of anti-apoptotic BFL-1 to selectively neutralize its oncogenic activity using a covalent stapled-peptide inhibitor. Here, we find that disulfide bonding between a native cysteine pair at the groove (C55) and C-terminal α9 helix (C175) of BFL-1 operates as a redox switch to control the accessibility of the anti-apoptotic pocket. Reducing the C55-C175 disulfide triggers α9 release, which promotes mitochondrial translocation, groove exposure for BH3 interaction and inhibition of mitochondrial permeabilization by pro-apoptotic BAX. C55-C175 disulfide formation in an oxidative cellular environment abrogates the ability of BFL-1 to bind BH3 domains. Thus, we identify a mechanism of conformational control of BFL-1 by an intramolecular redox switch."xsd:string |
| http://purl.uniprot.org/citations/32661419 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41594-020-0458-9"xsd:string |
| http://purl.uniprot.org/citations/32661419 | http://purl.uniprot.org/core/author | "Engen J.R."xsd:string |
| http://purl.uniprot.org/citations/32661419 | http://purl.uniprot.org/core/author | "Wales T.E."xsd:string |
| http://purl.uniprot.org/citations/32661419 | http://purl.uniprot.org/core/author | "Bird G.H."xsd:string |
| http://purl.uniprot.org/citations/32661419 | http://purl.uniprot.org/core/author | "Walensky L.D."xsd:string |
| http://purl.uniprot.org/citations/32661419 | http://purl.uniprot.org/core/author | "Korshavn K.J."xsd:string |
| http://purl.uniprot.org/citations/32661419 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/32661419 | http://purl.uniprot.org/core/name | "Nat Struct Mol Biol"xsd:string |
| http://purl.uniprot.org/citations/32661419 | http://purl.uniprot.org/core/pages | "781-789"xsd:string |
| http://purl.uniprot.org/citations/32661419 | http://purl.uniprot.org/core/title | "A redox switch regulates the structure and function of anti-apoptotic BFL-1."xsd:string |
| http://purl.uniprot.org/citations/32661419 | http://purl.uniprot.org/core/volume | "27"xsd:string |
| http://purl.uniprot.org/citations/32661419 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/32661419 |
| http://purl.uniprot.org/citations/32661419 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/32661419 |
| http://purl.uniprot.org/uniprot/#_Q16548-mappedCitation-32661419 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32661419 |
| http://purl.uniprot.org/uniprot/Q16548 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/32661419 |