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dc.contributor.authorGuarente, Leonard Pershing
dc.contributor.authorAkieda-Asai, Sayaka
dc.contributor.authorZaima, Nobuhiro
dc.contributor.authorIkegami, Koji
dc.contributor.authorKahyo, Tomoaki
dc.contributor.authorYao, Ikuko
dc.contributor.authorHatanaka, Takahiro
dc.contributor.authorIemura, Shun-ichiro
dc.contributor.authorSugiyama, Rika
dc.contributor.authorYokozeki, Takeaki
dc.contributor.authorEishi, Yoshinobu
dc.contributor.authorKoike, Morio
dc.contributor.authorIkeda, Kyoji
dc.contributor.authorChiba, Takuya
dc.contributor.authorYamaza, Haruyoshi
dc.contributor.authorShimokawa, Isao
dc.contributor.authorSong, Si-Young
dc.contributor.authorMatsuno, Akira
dc.contributor.authorMizutani, Akiko
dc.contributor.authorSawabe, Motoji
dc.contributor.authorChao, Moses V.
dc.contributor.authorTanaka, Masashi
dc.contributor.authorKanaho, Yasunori
dc.contributor.authorNatsume, Tohru
dc.contributor.authorSugimura, Haruhiko
dc.contributor.authorDate, Yukari
dc.contributor.authorMcBurney, Michael W.
dc.contributor.authorSetou, Mitsutoshi
dc.date.accessioned2010-12-21T22:25:02Z
dc.date.available2010-12-21T22:25:02Z
dc.date.issued2010-07
dc.date.submitted2010-04
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/1721.1/60353
dc.description.abstractBackground: SIRT1, a NAD-dependent deacetylase, has diverse roles in a variety of organs such as regulation of endocrine function and metabolism. However, it remains to be addressed how it regulates hormone release there. Methodology/Principal Findings: Here, we report that SIRT1 is abundantly expressed in pituitary thyrotropes and regulates thyroid hormone secretion. Manipulation of SIRT1 level revealed that SIRT1 positively regulated the exocytosis of TSH-containing granules. Using LC/MS-based interactomics, phosphatidylinositol-4-phosphate 5-kinase (PIP5K)γ[subscript gamma] was identified as a SIRT1 binding partner and deacetylation substrate. SIRT1 deacetylated two specific lysine residues (K265/K268) in PIP5Kγ[subscript gamma] and enhanced PIP5Kγ[subscript gamma] enzyme activity. SIRT1-mediated TSH secretion was abolished by PIP5Kγ[subscript gamma] knockdown. SIRT1 knockdown decreased the levels of deacetylated PIP5Kγ, PI(4,5)P[subscript 2], and reduced the secretion of TSH from pituitary cells. These results were also observed in SIRT1-knockout mice. Conclusions/Significance: Our findings indicated that the control of TSH release by the SIRT1-PIP5Kγ[subscript gamma] pathway is important for regulating the metabolism of the whole body.en_US
dc.description.sponsorshipMitsubishi Institute of Life Sciencesen_US
dc.description.sponsorshipJapan Society for the Promotion of Science. (WAKATE S grant)en_US
dc.language.isoen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofhttp://dx.doi.org/10.1371/journal.pone.0011755en_US
dc.rightsCreative Commons Attributionen_US
dc.rights.urihttp://creativecommons.org/licenses/by/2.5/en_US
dc.sourcePLoSen_US
dc.titleSIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kγ[subscript gamma] Activity through Deacetylation of Specific Lysine Residues in Mammalsen_US
dc.typeArticleen_US
dc.identifier.citationAkieda-Asai, Sayaka et al. “SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kγ Activity through Deacetylation of Specific Lysine Residues in Mammals.” Ed. Mikhail V. Blagosklonny. PLoS ONE 5.7 (2010): e11755.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.approverGuarente, Leonard Pershing
dc.contributor.mitauthorGuarente, Leonard Pershing
dc.relation.journalPLoS ONEen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsAkieda-Asai, Sayaka; Zaima, Nobuhiro; Ikegami, Koji; Kahyo, Tomoaki; Yao, Ikuko; Hatanaka, Takahiro; Iemura, Shun-ichiro; Sugiyama, Rika; Yokozeki, Takeaki; Eishi, Yoshinobu; Koike, Morio; Ikeda, Kyoji; Chiba, Takuya; Yamaza, Haruyoshi; Shimokawa, Isao; Song, Si-Young; Matsuno, Akira; Mizutani, Akiko; Sawabe, Motoji; Chao, Moses V.; Tanaka, Masashi; Kanaho, Yasunori; Natsume, Tohru; Sugimura, Haruhiko; Date, Yukari; McBurney, Michael W.; Guarente, Leonard; Setou, Mitsutoshien
dc.identifier.orcidhttps://orcid.org/0000-0003-4064-2510
mit.licensePUBLISHER_CCen_US


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