@article{1cf49ac375044b0f8ae0bcace36fde15,
title = "An Insulin-Responsive Sensor in the SIRT1 Disordered Region Binds DBC1 and PACS-2 to Control Enzyme Activity",
abstract = "The disordered SIRT1 N-terminal region contains an insulin-responsive sensor (IRS), comprising an acidic cluster (AC) and a 3-helix bundle (3HB), controlling enzyme activity. Insulin triggers DBC1 and PACS-2 binding to the IRS. DBC1 removes the protective shield that hides the IRS, enabling PACS-2 to bind the acidic cluster and the 3-helix bundle, inhibiting SIRT1.",
keywords = "3-helix bundle, AKT, FGF21, NMR spectroscopy, PACS2, PGC-1alpha, PPARalpha, STACs, diet-induced obesity, liver, nuclear magnetic resonance spectroscopy, small molecule sirtuin-activating compounds",
author = "Krzysiak, {Troy C.} and Laurel Thomas and Choi, {You Jin} and Sylvain Auclair and Yiqi Qian and Shan Luan and Krasnow, {Stephanie M.} and Thomas, {Laura L.} and Koharudin, {Leonardus M.I.} and Benos, {Panayiotis V.} and Marks, {Daniel L.} and Gronenborn, {Angela M.} and Gary Thomas",
note = "Funding Information: This work was supported by NIH grants R01 DK114855 (to A.M.G. and G.T.), DK112844 (to G.T.), DK070333 (to D.L.M.), R01 LM012087, and U01 HL137159 (to P.V.B.) and the University of Pittsburgh Aging Institute (to T.C.K. and S.L.). The authors thank T. Brosenitsch for critically reading and editing the manuscript and Drs. M. Jurczak (University of Pittsburgh), A. O'Donnell (University of Pittsburgh), K. Nejak-Bowen (University of Pittsburgh), P. Thibodeau (University of Pittsburgh), U. Shinde (OHSU), B. Hubbard (U. Alberta), X. Li (NIEHS), B. Spiegelman (Yale), and J. Chung (NIH) for reagents and helpful discussions. Mike Delk (University of Pittsburgh) is acknowledged for NMR technical support and S. Klingensmith (University of Pittsburgh) for producing the animations. Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",
year = "2018",
month = dec,
day = "20",
doi = "10.1016/j.molcel.2018.10.007",
language = "English (US)",
volume = "72",
pages = "985--998.e7",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "6",
}