Human immunodeficiency virus type 1 Tat binding protein-1 is a transcriptional coactivator specific for TR.
The DNA-binding domain of nuclear hormone receptors functions as an interaction interface for other transcription factors. Using the DNA-binding domain of TRbeta1 as bait in the yeast two-hybrid system, we cloned the Tat binding protein-1 that was originally isolated as a protein binding to the human immunodeficiency virus type 1 Tat transactivator. Tat binding protein-1 has subsequently been identified as a member of the ATPase family and a component of the 26S proteasome. Tat binding protein-1 interacted with the DNA-binding domain but not with the ligand binding domain of TR in vivo and in vitro. TR bound to the amino-terminal portion of Tat binding protein-1 that contains a leucine zipper-like structure. In mammalian cells, Tat binding protein-1 potentiated the ligand-dependent transactivation by TRbeta1 and TRalpha1 via thyroid hormone response elements. Both the intact DNA-binding domain and activation function-2 of the TR were required for the transcriptional enhancement in the presence of Tat binding protein-1. Tat binding protein-1 did not augment the transactivation function of the RAR, RXR, PPARgamma, or ER. The intrinsic activation domain in Tat binding protein-1 resided within the carboxyl-terminal conserved ATPase domain, and a mutation of a putative ATP binding motif but not a helicase motif in the carboxyl-terminal conserved ATPase domain abolished the activation function. Tat binding protein-1 synergistically activated the TR-mediated transcription with the steroid receptor coactivator 1, p120, and cAMP response element-binding protein, although Tat binding protein-1 did not directly interact with these coactivators in vitro. In contrast, the N-terminal portion of Tat binding protein-1 directly interacted in vitro and in vivo with the TR-interacting protein 1 possessing an ATPase activity that interacts with the activation function-2 of liganded TR. Collectively, Tat binding protein-1 might function as a novel DNA-binding domain-binding transcriptional coactivator specific for the TR probably in cooperation with other activation function-2-interacting cofactors such as TR-interacting protein 1.
Ishizuka
T
T
First Department of Internal Medicine, Gunma University School of Medicine 3-39-15, Maebashi 371-8511, Japan.
Satoh
T
T
Monden
T
T
Shibusawa
N
N
Hashida
T
T
Yamada
M
M
Mori
M
M
D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000737:chemistry; D000255:Adenosine Triphosphate / Q000378:metabolism; D001665:Binding Sites; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D019281:Dimerization; D004357:Drug Synergism; D005656:Fungal Proteins / Q000235:genetics; D015870:Gene Expression; D005982:Glutathione Transferase / Q000235:genetics; D015497:HIV-1 / Q000737:chemistry*; D017405:Herpes Simplex Virus Protein Vmw65 / Q000235:genetics; D006801:Humans; D008156:Luciferases / Q000235:genetics; D046988:Proteasome Endopeptidase Complex; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011993:Recombinant Fusion Proteins; D020218:Response Elements; D029701:Saccharomyces cerevisiae Proteins; D013963:Thyroid Hormones / Q000494:pharmacology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation; D014162:Transfection
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D017405:Herpes Simplex Virus Protein Vmw65; D011988:Receptors, Thyroid Hormone; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D013963:Thyroid Hormones; D015534:Trans-Activators; D014157:Transcription Factors; D000255:Adenosine Triphosphate; D004247:DNA; D008156:Luciferases; D005982:Glutathione Transferase; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities; C064757:PSMC3 protein, human