Activation function-1 domain of androgen receptor contributes to the interaction between two distinct subnuclear compartments

• Published in: Journal of steroid biochemistry and molecular biology Vol. 85; no. 2; pp. 201 - 208
• Main Authors: Goto, Kiminobu, Zhao, Yue, Saito, Masayuki, Tomura, Arihiro, Morinaga, Hidetaka, Nomura, Masatoshi, Okabe, Taijiro, Yanase, Toshihiko, Takayanagi, Ryoichi, Nawata, Hajime
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Oxford Elsevier Ltd 01.06.2003; Elsevier Science
• Subjects: Activation function-1; Androgen receptor; Binding Sites; Biological and medical sciences; Cell Nucleus - physiology; Cells, Cultured; Cloning, Molecular; Fibroblasts - cytology; Fibroblasts - physiology; Genes, Reporter; Gynecology. Andrology. Obstetrics; Humans; Male and female genital diseases. Gonadal dysgenesis. Hermaphroditism. Sex hormones resistance; Medical sciences; Organelles - physiology; Receptors, Androgen - chemistry; Receptors, Androgen - physiology; Receptors, Glucocorticoid - chemistry; Receptors, Glucocorticoid - physiology; Recombinant Proteins - chemistry; Recombinant Proteins - metabolism; Saccharomyces cerevisiae - physiology; Skin - cytology; Splicing factor compartment; Transcriptional Activation; Transfection; Splicing factor compartment; Activation function-1; Androgen receptor; Human; Androgen; Monkey; Molecular interaction; Splicing factor; In vitro; Male pseudohermaphroditism; Kidney; Genetic disease; Target tissue resistance; Signal transduction; Vertebrata; Mammalia; Cell line; Primates; Transcription factor; Male genital diseases; Prostate; Biological receptor
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/S0960-0760(03)00196-1

The nucleus contains different sets of functional compartments often called “speckles”. The splicing factor compartment (SFC) has been speculated to consist of SFs and transcription factors, which thus make transcription-splicing coupling possible at the periphery of SFC. Androgen receptor (AR), as well as glucocorticoid receptor (GR), is unique since most, if not all, of its activities are mediated via the constitutive activity of the activation function-1 (AF-1) function. Transcriptionally active AR produces 250–400 subnuclear fine speckles11 shared with GR or estrogen receptor (ER), which colocalize with chiefly activation function-2 (AF-2)-interacting p160 family- or CBP-related speckles. We herein report the isolation of ANT-1 (AR N-terminal domain (NTD) transactivating protein-1) enhancing autonomous AF-1 transactivation function of AR or GR, but not of estrogen receptor α (ERα). The ANT-1 was identical to a binding protein of human splicing factor U5 snRNP (U5 snRNP-associated protein). ANT-1 was compartmentalized into 15–20 coarse SFC speckles which were spatially distinct from but surrounded by the AR compartments. Our results suggest that ANT-1 may play a key role in the molecular interaction between two spatially distinct subnuclear compartments in a receptor-specific fashion, and thereby induce the strong autonomous transactivation functions either of AR- or GR-AF-1.