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>