Thyroid hormones (THs) play a critical role in the metabolic phenotype of the heart; and most of the effects involve transcriptional regulation via thyroid hormone receptors (TRs). TRs ability to form combinatorial complexes with an array of partners accounts for TRs physiological flexibility in modulating gene expression. To identify proteins that associate with TRβ1 in the heart we performed a pull-down assay on cardiac tissue using GST-TRβ1 as bait and identified the bound proteins by LC MS/MS. ACAA2, a mitochondrial thiolase enzyme, was identified as a novel interacting protein. We confirmed ACAA2 localized to the nucleus and using a luciferase reporter assay showed ACAA2 acted as a TH-dependent coactivator for TRβ1. ACAA2 showed an ability to bind to TR recognition sequences but did not alter TRβ1 DNA binding ability. Thus, ACAA2 as a novel TRβ1 associating protein opens a new paradigm to understanding how TH/TRs may be manipulated by energetic pathway molecules.

甲状腺激素 (THs) 在心脏的代谢表型中起关键作用；大多数影响涉及通过甲状腺激素受体 (TRs) 进行的转录调节。TRs 与一系列合作伙伴形成组合复合物的能力解释了 TRs 在调节基因表达方面的生理灵活性。为了鉴定与心脏中的 TRβ1 相关的蛋白质，我们使用 GST-TRβ1 作为诱饵对心脏组织进行了下拉测定，并通过 LC MS/MS 鉴定了结合的蛋白质。ACAA2 是一种线粒体硫解酶，被鉴定为一种新型的相互作用蛋白。我们证实了 ACAA2 定位于细胞核，并使用荧光素酶报告基因测定显示 ACAA2 作为 TRβ1 的 TH 依赖性共激活剂。ACAA2 显示出与 TR 识别序列结合的能力，但不改变 TRβ1 DNA 结合能力。因此，