http://purl.uniprot.org/citations/15485396 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/15485396 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/15485396 | http://www.w3.org/2000/01/rdf-schema#comment | "ML-IAP (melanoma inhibitor of apoptosis) is a potent anti-apoptotic protein that is strongly up-regulated in melanoma and confers protection against a variety of pro-apoptotic stimuli. The mechanism by which ML-IAP regulates apoptosis is unclear, although weak inhibition of caspases 3 and 9 has been reported. Here, the binding to and inhibition of caspase 9 by the single BIR (baculovirus IAP repeat) domain of ML-IAP has been investigated and found to be significantly less potent than the ubiquitously expressed XIAP (X-linked IAP). Engineering of the ML-IAP-BIR domain, based on comparisons with the third BIR domain of XIAP, resulted in a chimeric BIR domain that binds to and inhibits caspase 9 significantly better than either ML-IAP-BIR or XIAP-BIR3. Mutational analysis of the ML-IAP-BIR domain demonstrated that similar enhancements in caspase 9 affinity can be achieved with only three amino acid substitutions. However, none of these modifications affected binding of the ML-IAP-BIR domain to the IAP antagonist Smac (second mitochondrial activator of caspases). ML-IAP-BIR was found to bind mature Smac with low nanomolar affinity, similar to that of XIAP-BIR2-BIR3. Correspondingly, increased expression of ML-IAP results in formation of a ML-IAP-Smac complex and disruption of the endogenous interaction between XIAP and mature Smac. These results suggest that ML-IAP might regulate apoptosis by sequestering Smac and preventing it from antagonizing XIAP-mediated inhibition of caspases, rather than by direct inhibition of caspases."xsd:string |
http://purl.uniprot.org/citations/15485396 | http://purl.org/dc/terms/identifier | "doi:10.1042/bj20041108"xsd:string |
http://purl.uniprot.org/citations/15485396 | http://purl.org/dc/terms/identifier | "doi:10.1042/bj20041108"xsd:string |
http://purl.uniprot.org/citations/15485396 | http://purl.uniprot.org/core/author | "Franklin M.C."xsd:string |
http://purl.uniprot.org/citations/15485396 | http://purl.uniprot.org/core/author | "Franklin M.C."xsd:string |
http://purl.uniprot.org/citations/15485396 | http://purl.uniprot.org/core/author | "Shin H."xsd:string |
http://purl.uniprot.org/citations/15485396 | http://purl.uniprot.org/core/author | "Shin H."xsd:string |
http://purl.uniprot.org/citations/15485396 | http://purl.uniprot.org/core/author | "Salvesen G.S."xsd:string |
http://purl.uniprot.org/citations/15485396 | http://purl.uniprot.org/core/author | "Salvesen G.S."xsd:string |
http://purl.uniprot.org/citations/15485396 | http://purl.uniprot.org/core/author | "Das K."xsd:string |
http://purl.uniprot.org/citations/15485396 | http://purl.uniprot.org/core/author | "Das K."xsd:string |
http://purl.uniprot.org/citations/15485396 | http://purl.uniprot.org/core/author | "Kadkhodayan S."xsd:string |
http://purl.uniprot.org/citations/15485396 | http://purl.uniprot.org/core/author | "Kadkhodayan S."xsd:string |
http://purl.uniprot.org/citations/15485396 | http://purl.uniprot.org/core/author | "Fairbrother W.J."xsd:string |
http://purl.uniprot.org/citations/15485396 | http://purl.uniprot.org/core/author | "Fairbrother W.J."xsd:string |
http://purl.uniprot.org/citations/15485396 | http://purl.uniprot.org/core/author | "Vucic D."xsd:string |
http://purl.uniprot.org/citations/15485396 | http://purl.uniprot.org/core/author | "Vucic D."xsd:string |
http://purl.uniprot.org/citations/15485396 | http://purl.uniprot.org/core/author | "Deshayes K."xsd:string |
http://purl.uniprot.org/citations/15485396 | http://purl.uniprot.org/core/author | "Deshayes K."xsd:string |
http://purl.uniprot.org/citations/15485396 | http://purl.uniprot.org/core/author | "Eckelman B.P."xsd:string |
http://purl.uniprot.org/citations/15485396 | http://purl.uniprot.org/core/author | "Eckelman B.P."xsd:string |
http://purl.uniprot.org/citations/15485396 | http://purl.uniprot.org/core/author | "Elliott L.O."xsd:string |
http://purl.uniprot.org/citations/15485396 | http://purl.uniprot.org/core/author | "Elliott L.O."xsd:string |