Wang W, Ledee D

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 ...

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that associate with TR?1 in the heart we performed a pull-down assay on cardiac tissue using GST-TR?1 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 TR?1. ACAA2 showed an ability to bind to TR recognition sequences but did not alter TR?1 DNA binding ability. Thus, ACAA2 as a novel TR?1 associating protein opens a new paradigm to understanding how TH/TRs may be manipulated by energetic pathway molecules.

Date: Oct. 22, 2021

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