dc.contributor.author | Guarente, Leonard Pershing | |
dc.contributor.author | Akieda-Asai, Sayaka | |
dc.contributor.author | Zaima, Nobuhiro | |
dc.contributor.author | Ikegami, Koji | |
dc.contributor.author | Kahyo, Tomoaki | |
dc.contributor.author | Yao, Ikuko | |
dc.contributor.author | Hatanaka, Takahiro | |
dc.contributor.author | Iemura, Shun-ichiro | |
dc.contributor.author | Sugiyama, Rika | |
dc.contributor.author | Yokozeki, Takeaki | |
dc.contributor.author | Eishi, Yoshinobu | |
dc.contributor.author | Koike, Morio | |
dc.contributor.author | Ikeda, Kyoji | |
dc.contributor.author | Chiba, Takuya | |
dc.contributor.author | Yamaza, Haruyoshi | |
dc.contributor.author | Shimokawa, Isao | |
dc.contributor.author | Song, Si-Young | |
dc.contributor.author | Matsuno, Akira | |
dc.contributor.author | Mizutani, Akiko | |
dc.contributor.author | Sawabe, Motoji | |
dc.contributor.author | Chao, Moses V. | |
dc.contributor.author | Tanaka, Masashi | |
dc.contributor.author | Kanaho, Yasunori | |
dc.contributor.author | Natsume, Tohru | |
dc.contributor.author | Sugimura, Haruhiko | |
dc.contributor.author | Date, Yukari | |
dc.contributor.author | McBurney, Michael W. | |
dc.contributor.author | Setou, Mitsutoshi | |
dc.date.accessioned | 2010-12-21T22:25:02Z | |
dc.date.available | 2010-12-21T22:25:02Z | |
dc.date.issued | 2010-07 | |
dc.date.submitted | 2010-04 | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/60353 | |
dc.description.abstract | Background:
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.sponsorship | Mitsubishi Institute of Life Sciences | en_US |
dc.description.sponsorship | Japan Society for the Promotion of Science. (WAKATE S grant) | en_US |
dc.language.iso | en_US | |
dc.publisher | Public Library of Science | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1371/journal.pone.0011755 | en_US |
dc.rights | Creative Commons Attribution | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by/2.5/ | en_US |
dc.source | PLoS | en_US |
dc.title | SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kγ[subscript gamma] Activity through Deacetylation of Specific Lysine Residues in Mammals | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Akieda-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.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.approver | Guarente, Leonard Pershing | |
dc.contributor.mitauthor | Guarente, Leonard Pershing | |
dc.relation.journal | PLoS ONE | en_US |
dc.eprint.version | Final published version | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Akieda-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, Mitsutoshi | en |
dc.identifier.orcid | https://orcid.org/0000-0003-4064-2510 | |
mit.license | PUBLISHER_CC | en_US |
mit.metadata.status | Complete | |