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rdf:type |
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lifeskim:mentions |
umls-concept:C0015127,
umls-concept:C0026882,
umls-concept:C0033684,
umls-concept:C0086418,
umls-concept:C0205245,
umls-concept:C0521451,
umls-concept:C0679058,
umls-concept:C1314792,
umls-concept:C1427590,
umls-concept:C1547699,
umls-concept:C1842138,
umls-concept:C2700640
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pubmed:issue |
1
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pubmed:dateCreated |
2011-7-18
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pubmed:abstractText |
SMAC/DIABLO is a mitochondrial proapoptotic protein that is released from mitochondria during apoptosis and counters the inhibitory activities of inhibitor of apoptosis proteins, IAPs. By linkage analysis and candidate screening, we identified a heterozygous SMAC/DIABLO mutation, c.377C>T (p.Ser126Leu, refers to p.Ser71Leu in the mature protein) in a six-generation Chinese kindred characterized by dominant progressive nonsyndromic hearing loss, designated as DFNA64. SMAC/DIABLO is highly expressed in human embryonic ears and is enriched in the developing mouse inner-ear hair cells, suggesting it has a role in the development and homeostasis of hair cells. We used a functional study to demonstrate that the SMAC/DIABLO(S71L) mutant, while retaining the proapoptotic function, triggers significant degradation of both wild-type and mutant SMAC/DIABLO and renders host mitochondria susceptible to calcium-induced loss of the membrane potential. Our work identifies DFNA64 as the human genetic disorder associated with SMAC/DIABLO malfunction and suggests that mutant SMAC/DIABLO(S71L) might cause mitochondrial dysfunction.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1537-6605
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pubmed:author |
pubmed-author:AhoAA,
pubmed-author:ChenJingJ,
pubmed-author:ChenZheng-YiZY,
pubmed-author:ChengJingJ,
pubmed-author:FuY PYP,
pubmed-author:HanBingB,
pubmed-author:HanDongyiD,
pubmed-author:HeSudanS,
pubmed-author:LiHuaweiH,
pubmed-author:LiuXuezhongX,
pubmed-author:LuYanpingY,
pubmed-author:PetrilloMarcoM,
pubmed-author:WrzeszczynskiKazimierz OKO,
pubmed-author:YangShimingS,
pubmed-author:YuanHuijunH,
pubmed-author:ZhaiSuoqiangS,
pubmed-author:ZhangMichael QMQ,
pubmed-author:ZhuYuhuaY
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pubmed:copyrightInfo |
Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
89
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
56-66
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pubmed:meshHeading |
pubmed-meshheading:21722859-Adolescent,
pubmed-meshheading:21722859-Adult,
pubmed-meshheading:21722859-Age of Onset,
pubmed-meshheading:21722859-Aged,
pubmed-meshheading:21722859-Amino Acid Sequence,
pubmed-meshheading:21722859-Animals,
pubmed-meshheading:21722859-Apoptosis,
pubmed-meshheading:21722859-Asian Continental Ancestry Group,
pubmed-meshheading:21722859-DNA Mutational Analysis,
pubmed-meshheading:21722859-Down-Regulation,
pubmed-meshheading:21722859-Female,
pubmed-meshheading:21722859-Gene Expression Regulation, Developmental,
pubmed-meshheading:21722859-Genetic Linkage,
pubmed-meshheading:21722859-HeLa Cells,
pubmed-meshheading:21722859-Hearing Loss,
pubmed-meshheading:21722859-Humans,
pubmed-meshheading:21722859-Immunohistochemistry,
pubmed-meshheading:21722859-Immunoprecipitation,
pubmed-meshheading:21722859-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:21722859-Male,
pubmed-meshheading:21722859-Membrane Potentials,
pubmed-meshheading:21722859-Mice,
pubmed-meshheading:21722859-Middle Aged,
pubmed-meshheading:21722859-Mitochondrial Proteins,
pubmed-meshheading:21722859-Molecular Sequence Data,
pubmed-meshheading:21722859-Mutagenesis, Site-Directed,
pubmed-meshheading:21722859-Mutation, Missense,
pubmed-meshheading:21722859-Pedigree,
pubmed-meshheading:21722859-Polymorphism, Single Nucleotide,
pubmed-meshheading:21722859-RNA, Small Interfering,
pubmed-meshheading:21722859-Up-Regulation,
pubmed-meshheading:21722859-Young Adult
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pubmed:year |
2011
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pubmed:articleTitle |
Functional mutation of SMAC/DIABLO, encoding a mitochondrial proapoptotic protein, causes human progressive hearing loss DFNA64.
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pubmed:affiliation |
Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China.
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pubmed:publicationType |
Journal Article,
Case Reports,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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