title: Roles of proteasomal 19S regulatory particles in promoter loading of thyroid hormone receptor.
abstract: 19S regulatory particles (19SRP) of 26S proteasome participate in multiple steps of gene transcription in yeast. We previously showed that Tat-binding protein-1 (TBP-1), an ATPase of 19SRP, interacts with thyroid hormone receptor (TR) and enhances TR-mediated transcription synergistically with steroid receptor coactivator-1 (SRC-1). To further elucidate the roles of ATPases and a non-ATPase component of 19SRP in gene regulation by TR, we investigated whether knockdown (KO) of TBP-1, TRIP1 or Rpn10 using small interfering RNA affects TR-mediated transactivation in HeLa cells. KO of individual subunits attenuated TR-mediated transactivation through the thyroid hormone response element (TRE) in the absence or presence of cotransfected SRC-1 without altering TR and SRC-1 protein levels. KO of TBP-1 disrupted ligand-induced loading of TR, SRC-1, and RNA polymerase II in chromatin immunoprecipitation assays. Collectively, both ATPase and non-ATPase components of 19SRP play critical roles in TR-mediated transactivation by coordinating the proper loading of liganded TR to TRE.
authors: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi 371-8511, Japan. tsato@showa.gunma-u.ac.jp
authors: Tetsurou
authors: T
authors: Satoh
authors: Takahiro
authors: T
authors: Ishizuka
authors: Satoshi
authors: S
authors: Yoshino
authors: Takuya
authors: T
authors: Tomaru
authors: Yasuyo
authors: Y
authors: Nakajima
authors: Nobuyuki
authors: N
authors: Shibusawa
authors: Koshi
authors: K
authors: Hashimoto
authors: Masanobu
authors: M
authors: Yamada
authors: Masatomo
authors: M
authors: Mori
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D039621:Eukaryotic Initiation Factor-3 / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D011401:Promoter Regions, Genetic; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D039621:Eukaryotic Initiation Factor-3; C498506:PSMD4 protein, human; D016601:RNA-Binding Proteins; D011988:Receptors, Thyroid Hormone; C096013:EIF3I protein, human; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities; C064757:PSMC3 protein, human