1tw6: Difference between revisions
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{{STRUCTURE_1tw6| PDB=1tw6 | SCENE= }} | {{STRUCTURE_1tw6| PDB=1tw6 | SCENE= }} | ||
===Structure of an ML-IAP/XIAP chimera bound to a 9mer peptide derived from Smac=== | |||
{{ABSTRACT_PUBMED_15485396}} | |||
=== | ==Disease== | ||
[[http://www.uniprot.org/uniprot/DBLOH_HUMAN DBLOH_HUMAN]] Defects in DIABLO are the cause of deafness autosomal dominant type 64 (DFNA64) [MIM:[http://omim.org/entry/614152 614152]]. DFNA64 is a form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.<ref>PMID:21722859</ref> | |||
==Function== | |||
[[http://www.uniprot.org/uniprot/BIRC7_HUMAN BIRC7_HUMAN]] Apoptotic regulator capable of exerting proapoptotic and anti-apoptotic activities and plays crucial roles in apoptosis, cell proliferation, and cell cycle control. Its anti-apoptotic activity is mediated through the inhibition of CASP3, CASP7 and CASP9, as well as by its E3 ubiquitin-protein ligase activity. As it is a weak caspase inhibitor, its anti-apoptotic activity is thought to be due to its ability to ubiquitinate DIABLO/SMAC targeting it for degradation thereby promoting cell survival. May contribute to caspase inhibition, by blocking the ability of DIABLO/SMAC to disrupt XIAP/BIRC4-caspase interactions. Protects against apoptosis induced by TNF or by chemical agents such as adriamycin, etoposide or staurosporine. Suppression of apoptosis is mediated by activation of MAPK8/JNK1, and possibly also of MAPK9/JNK2. This activation depends on TAB1 and NR2C2/TAK1. In vitro, inhibits CASP3 and proteolytic activation of pro-CASP9. Isoform 1 blocks staurosporine-induced apoptosis. Isoform 2 blocks etoposide-induced apoptosis. Isoform 2 protects against natural killer (NK) cell killing whereas isoform 1 augments killing.<ref>PMID:11084335</ref><ref>PMID:16729033</ref><ref>PMID:17294084</ref><ref>PMID:18034418</ref> [[http://www.uniprot.org/uniprot/DBLOH_HUMAN DBLOH_HUMAN]] Promotes apoptosis by activating caspases in the cytochrome c/Apaf-1/caspase-9 pathway. Acts by opposing the inhibitory activity of inhibitor of apoptosis proteins (IAP). Inhibits the activity of BIRC6/bruce by inhibiting its binding to caspases. Isoform 3 attenuates the stability and apoptosis-inhibiting activity of XIAP/BIRC4 by promoting XIAP/BIRC4 ubiquitination and degradation through the ubiquitin-proteasome pathway. Isoform 3 also disrupts XIAP/BIRC4 interacting with processed caspase-9 and promotes caspase-3 activation. Isoform 1 is defective in the capacity to down-regulate the XIAP/BIRC4 abundance.<ref>PMID:10929711</ref><ref>PMID:14523016</ref><ref>PMID:15200957</ref> | |||
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
<ref group="xtra">PMID:015485396</ref><ref group="xtra">PMID:012846571</ref><ref group="xtra">PMID:012620238</ref><references group="xtra"/> | <ref group="xtra">PMID:015485396</ref><ref group="xtra">PMID:012846571</ref><ref group="xtra">PMID:012620238</ref><references group="xtra"/><references/> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Das, K.]] | [[Category: Das, K.]] | ||
