title: Activation function-1 domain of androgen receptor contributes to the interaction between two distinct subnuclear compartments.
abstract: 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 alpha (ERalpha). 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.
authors.affiliation: Department of Medicine and Bioregulatory Science (3rd Department of Internal Medicine), Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan. kgotou@intmed3.med.kyushu-u.ac.jp
authors.forename: Kiminobu
authors.initials: K
authors.lastname: Goto
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.forename: Masayuki
authors.initials: M
authors.lastname: Saito
authors.forename: Arihiro
authors.initials: A
authors.lastname: Tomura
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Morinaga
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Nomura
authors.forename: Taijiro
authors.initials: T
authors.lastname: Okabe
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yanase
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Takayanagi
authors.forename: Hajime
authors.initials: H
authors.lastname: Nawata
mesh_terms: D001665:Binding Sites; D002467:Cell Nucleus / Q000502:physiology*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D017930:Genes, Reporter; D006801:Humans; D015388:Organelles / Q000502:physiology; D011944:Receptors, Androgen / Q000737:chemistry* / Q000502:physiology*; D011965:Receptors, Glucocorticoid / Q000737:chemistry / Q000502:physiology; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000502:physiology; D012867:Skin / Q000166:cytology; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D011944:Receptors, Androgen; D011965:Receptors, Glucocorticoid; D011994:Recombinant Proteins