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Article: SIRT6 regulates TNF-α secretion through hydrolysis of long-chain fatty acyl lysine

TitleSIRT6 regulates TNF-α secretion through hydrolysis of long-chain fatty acyl lysine
Authors
Issue Date2013
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/nature
Citation
Nature, 2013, v. 496, p. 110-113 How to Cite?
AbstractThe Sir2 family of enzymes or sirtuins are known as nicotinamide adenine dinucleotide (NAD)-dependent deacetylases and have been implicated in the regulation of transcription, genome stability, metabolism and lifespan. However, four of the seven mammalian sirtuins have very weak deacetylase activity in vitro. Here we show that human SIRT6 efficiently removes long-chain fatty acyl groups, such as myristoyl, from lysine residues. The crystal structure of SIRT6 reveals a large hydrophobic pocket that can accommodate long-chain fatty acyl groups. We demonstrate further that SIRT6 promotes the secretion of tumour necrosis factor-α (TNF-α) by removing the fatty acyl modification on K19 and K20 of TNF-α. Protein lysine fatty acylation has been known to occur in mammalian cells, but the function and regulatory mechanisms of this modification were unknown. Our data indicate that protein lysine fatty acylation is a novel mechanism that regulates protein secretion. The discovery of SIRT6 as an enzyme that controls protein lysine fatty acylation provides new opportunities to investigate the physiological function of a protein post-translational modification that has been little studied until now. © 2013 Macmillan Publishers Limited. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/184041
ISSN
2015 Impact Factor: 38.138
2015 SCImago Journal Rankings: 21.936
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorJiang, H-
dc.contributor.authorKhan, S-
dc.contributor.authorWang, Y-
dc.contributor.authorCharron, G-
dc.contributor.authorSebastian, C-
dc.contributor.authorDu, JT-
dc.contributor.authorKim, R-
dc.contributor.authorGe, E-
dc.contributor.authorMostoslavsky, R-
dc.contributor.authorHang, HC-
dc.contributor.authorHao, Q-
dc.contributor.authorLin, HN-
dc.date.accessioned2013-06-18T05:08:51Z-
dc.date.available2013-06-18T05:08:51Z-
dc.date.issued2013-
dc.identifier.citationNature, 2013, v. 496, p. 110-113-
dc.identifier.issn0028-0836-
dc.identifier.urihttp://hdl.handle.net/10722/184041-
dc.description.abstractThe Sir2 family of enzymes or sirtuins are known as nicotinamide adenine dinucleotide (NAD)-dependent deacetylases and have been implicated in the regulation of transcription, genome stability, metabolism and lifespan. However, four of the seven mammalian sirtuins have very weak deacetylase activity in vitro. Here we show that human SIRT6 efficiently removes long-chain fatty acyl groups, such as myristoyl, from lysine residues. The crystal structure of SIRT6 reveals a large hydrophobic pocket that can accommodate long-chain fatty acyl groups. We demonstrate further that SIRT6 promotes the secretion of tumour necrosis factor-α (TNF-α) by removing the fatty acyl modification on K19 and K20 of TNF-α. Protein lysine fatty acylation has been known to occur in mammalian cells, but the function and regulatory mechanisms of this modification were unknown. Our data indicate that protein lysine fatty acylation is a novel mechanism that regulates protein secretion. The discovery of SIRT6 as an enzyme that controls protein lysine fatty acylation provides new opportunities to investigate the physiological function of a protein post-translational modification that has been little studied until now. © 2013 Macmillan Publishers Limited. All rights reserved.-
dc.languageeng-
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/nature-
dc.relation.ispartofNature-
dc.titleSIRT6 regulates TNF-α secretion through hydrolysis of long-chain fatty acyl lysine-
dc.typeArticle-
dc.identifier.emailWang, Y: wyhku83@hku.hk-
dc.identifier.emailHao, Q: qhao@hku.hk-
dc.identifier.authorityWang, Y=rp02093-
dc.identifier.authorityHao, Q=rp01332-
dc.identifier.doi10.1038/nature12038-
dc.identifier.pmid23552949-
dc.identifier.pmcidPMC3635073-
dc.identifier.scopuseid_2-s2.0-84875881601-
dc.identifier.hkuros214687-
dc.identifier.volume496-
dc.identifier.spage110-
dc.identifier.epage113-
dc.publisher.placeUnited Kingdom-
dc.identifier.f1000717996842-

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