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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
46
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pubmed:dateCreated |
2007-11-12
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pubmed:abstractText |
Sirtuins are homologues of the yeast transcriptional repressor Sir2p and are conserved from bacteria to humans. We report that human SIRT4 is localized to the mitochondria. SIRT4 is a matrix protein and becomes cleaved at amino acid 28 after import into mitochondria. Mass spectrometry analysis of proteins that coimmunoprecipitate with SIRT4 identified insulindegrading enzyme and the ADP/ATP carrier proteins, ANT2 and ANT3. SIRT4 exhibits no histone deacetylase activity but functions as an efficient ADP-ribosyltransferase on histones and bovine serum albumin. SIRT4 is expressed in islets of Langerhans and colocalizes with insulin-expressing beta cells. Depletion of SIRT4 from insulin-producing INS-1E cells results in increased insulin secretion in response to glucose. These observations define a new role for mitochondrial SIRT4 in the regulation of insulin secretion.
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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 |
Nov
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
16
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pubmed:volume |
282
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
33583-92
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:17715127-ADP Ribose Transferases,
pubmed-meshheading:17715127-Cell Line,
pubmed-meshheading:17715127-DNA, Complementary,
pubmed-meshheading:17715127-Glucose,
pubmed-meshheading:17715127-HeLa Cells,
pubmed-meshheading:17715127-Humans,
pubmed-meshheading:17715127-Immunoprecipitation,
pubmed-meshheading:17715127-Insulin,
pubmed-meshheading:17715127-Insulin-Secreting Cells,
pubmed-meshheading:17715127-Islets of Langerhans,
pubmed-meshheading:17715127-Mass Spectrometry,
pubmed-meshheading:17715127-Microscopy, Confocal,
pubmed-meshheading:17715127-Mitochondria,
pubmed-meshheading:17715127-Mitochondrial Proteins,
pubmed-meshheading:17715127-Plasmids,
pubmed-meshheading:17715127-RNA, Small Interfering,
pubmed-meshheading:17715127-Sirtuins,
pubmed-meshheading:17715127-Transfection
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pubmed:year |
2007
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pubmed:articleTitle |
Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase.
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pubmed:affiliation |
Gladstone Institute of Virology and Immunology, University of California, San Francisco, California 94158, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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