Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
46
pubmed:dateCreated
2000-12-29
pubmed:databankReference
pubmed:abstractText
Smac/DIABLO is a mitochondrial protein that is released along with cytochrome c during apoptosis and promotes cytochrome c-dependent caspase activation by neutralizing inhibitor of apoptosis proteins (IAPs). We provide evidence that Smac/DIABLO functions at the levels of both the Apaf-1-caspase-9 apoptosome and effector caspases. The N terminus of Smac/DIABLO is absolutely required for its ability to interact with the baculovirus IAP repeat (BIR3) of XIAP and to promote cytochrome c-dependent caspase activation. However, it is less critical for its ability to interact with BIR1/BIR2 of XIAP and to promote the activity of the effector caspases. Consistent with the ability of Smac/DIABLO to function at the level of the effector caspases, expression of a cytosolic Smac/DIABLO in Type II cells allowed TRAIL to bypass Bcl-xL inhibition of death receptor-induced apoptosis. Combined, these data suggest that Smac/DIABLO plays a critical role in neutralizing IAP inhibition of the effector caspases in the death receptor pathway of Type II cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins, http://linkedlifedata.com/resource/pubmed/chemical/BCL2L1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Bacterial Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Caspases, http://linkedlifedata.com/resource/pubmed/chemical/DIABLO protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Inhibitor of Apoptosis Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Insect Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides..., http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Mitochondrial Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms, http://linkedlifedata.com/resource/pubmed/chemical/Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor, http://linkedlifedata.com/resource/pubmed/chemical/TNF-Related Apoptosis-Inducing..., http://linkedlifedata.com/resource/pubmed/chemical/TNFSF10 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha, http://linkedlifedata.com/resource/pubmed/chemical/X-Linked Inhibitor of Apoptosis..., http://linkedlifedata.com/resource/pubmed/chemical/XIAP protein, human, http://linkedlifedata.com/resource/pubmed/chemical/bcl-X Protein
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
36152-7
pubmed:dateRevised
2008-5-14
pubmed:meshHeading
pubmed-meshheading:10950947-Amino Acid Sequence, pubmed-meshheading:10950947-Apoptosis, pubmed-meshheading:10950947-Apoptosis Regulatory Proteins, pubmed-meshheading:10950947-Bacterial Proteins, pubmed-meshheading:10950947-Carrier Proteins, pubmed-meshheading:10950947-Caspases, pubmed-meshheading:10950947-Cell Differentiation, pubmed-meshheading:10950947-Cytosol, pubmed-meshheading:10950947-Enzyme Activation, pubmed-meshheading:10950947-Humans, pubmed-meshheading:10950947-Inhibitor of Apoptosis Proteins, pubmed-meshheading:10950947-Insect Proteins, pubmed-meshheading:10950947-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:10950947-Membrane Glycoproteins, pubmed-meshheading:10950947-Mitochondria, pubmed-meshheading:10950947-Mitochondrial Proteins, pubmed-meshheading:10950947-Molecular Sequence Data, pubmed-meshheading:10950947-Mutation, pubmed-meshheading:10950947-Protein Binding, pubmed-meshheading:10950947-Protein Isoforms, pubmed-meshheading:10950947-Proteins, pubmed-meshheading:10950947-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:10950947-Receptors, Tumor Necrosis Factor, pubmed-meshheading:10950947-Signal Transduction, pubmed-meshheading:10950947-TNF-Related Apoptosis-Inducing Ligand, pubmed-meshheading:10950947-Transfection, pubmed-meshheading:10950947-Tumor Cells, Cultured, pubmed-meshheading:10950947-Tumor Necrosis Factor-alpha, pubmed-meshheading:10950947-X-Linked Inhibitor of Apoptosis Protein, pubmed-meshheading:10950947-bcl-X Protein
pubmed:year
2000
pubmed:articleTitle
Molecular determinants of the caspase-promoting activity of Smac/DIABLO and its role in the death receptor pathway.
pubmed:affiliation
Center for Apoptosis Research and the Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.