10.1371/journal.pone.0011755
Sayaka Akieda-Asai
Sayaka
Akieda-Asai
Nobuhiro Zaima
Nobuhiro
Zaima
Koji Ikegami
Koji
Ikegami
Tomoaki Kahyo
Tomoaki
Kahyo
Ikuko Yao
Ikuko
Yao
Takahiro Hatanaka
Takahiro
Hatanaka
Shun-ichiro Iemura
Shun-ichiro
Iemura
Rika Sugiyama
Rika
Sugiyama
Takeaki Yokozeki
Takeaki
Yokozeki
Yoshinobu Eishi
Yoshinobu
Eishi
Morio Koike
Morio
Koike
Kyoji Ikeda
Kyoji
Ikeda
Takuya Chiba
Takuya
Chiba
Haruyoshi Yamaza
Haruyoshi
Yamaza
Isao Shimokawa
Isao
Shimokawa
Si-Young Song
Si-Young
Song
Akira Matsuno
Akira
Matsuno
Akiko Mizutani
Akiko
Mizutani
Motoji Sawabe
Motoji
Sawabe
Moses V. Chao
Moses V.
Chao
Masashi Tanaka
Masashi
Tanaka
Yasunori Kanaho
Yasunori
Kanaho
Tohru Natsume
Tohru
Natsume
Haruhiko Sugimura
Haruhiko
Sugimura
Yukari Date
Yukari
Date
Michael W. McBurney
Michael
W. McBurney
Leonard Guarente
Leonard
Guarente
Mitsutoshi Setou
Mitsutoshi
Setou
SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kγ Activity through Deacetylation of Specific Lysine Residues in Mammals
Public Library of Science
2010
sirt1
regulates
thyroid-stimulating
enhancing
deacetylation
lysine
residues
mammals
2010-07-23 00:41:42
Dataset
https://plos.figshare.com/articles/dataset/SIRT1_Regulates_Thyroid_Stimulating_Hormone_Release_by_Enhancing_PIP5K_Activity_through_Deacetylation_of_Specific_Lysine_Residues_in_Mammals/142502
<div><h3>Background</h3><p>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.</p><h3>Methodology/Principal Findings</h3><p>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 was identified as a SIRT1 binding partner and deacetylation substrate. SIRT1 deacetylated two specific lysine residues (K265/K268) in PIP5Kγ and enhanced PIP5Kγ enzyme activity. SIRT1-mediated TSH secretion was abolished by PIP5Kγ knockdown. SIRT1 knockdown decreased the levels of deacetylated PIP5Kγ, PI(4,5)P<sub>2</sub>, and reduced the secretion of TSH from pituitary cells. These results were also observed in SIRT1-knockout mice.</p><h3>Conclusions/Significance</h3><p>Our findings indicated that the control of TSH release by the SIRT1-PIP5Kγ pathway is important for regulating the metabolism of the whole body.</p></div>