Activation function-1 domain of androgen receptor contributes to the interaction between two distinct subnuclear compartments.
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.
Goto
Kiminobu
K
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
Zhao
Yue
Y
Saito
Masayuki
M
Tomura
Arihiro
A
Morinaga
Hidetaka
H
Nomura
Masatoshi
M
Okabe
Taijiro
T
Yanase
Toshihiko
T
Takayanagi
Ryoichi
R
Nawata
Hajime
H
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
D011944:Receptors, Androgen; D011965:Receptors, Glucocorticoid; D011994:Recombinant Proteins