Activation function-1 domain of androgen receptor contributes to the interaction between two distinct subnuclear compartments
Activation function-1 domain of androgen receptor contributes to the interaction between two distinct subnuclear compartments
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DOI：
10.1016/s0960-0760(03)00196-1
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发表时间：
2003-06-01
影响因子：
4.1
通讯作者：
Nawatab, H
中科院分区：
文献类型：
--
作者：
Goto, K;Zhao, Y;Nawatab, H
细胞核包含不同组的功能区室，通常称为“斑点”。据推测，剪接因子区室 (SFC) 由 SF 和转录因子组成，从而使转录-剪接耦合在 SFC 的外围成为可能。雄激素受体 (AR) 以及糖皮质激素受体 (GR) 是独特的，因为其大多数（如果不是全部）活性是通过激活功能 1 (AF-1) 功能的组成性活性介导的。转录活跃的 AR 产生 250-400 个与 GR 或雌激素受体 (ER) 共享的亚核细斑点 11，它们与主要与激活功能 2 (AF-2) 相互作用的 p 160 家族或 CBP 相关斑点共定位。我们在此报告分离ANT-1（AR N端结构域（NTD）反式激活蛋白-1）增强AR或GR的自主AF-1反式激活功能，但不增强雌激素受体α（ERα）的自主性AF-1反式激活功能。 ANT-1与人剪接因子U5 snRNP的结合蛋白（U5 snRNP相关蛋白）相同。 ANT-1 被划分为 15-20 个粗 SFC 斑点，这些斑点在空间上与 AR 隔间不同但被 AR 隔间包围。我们的结果表明，ANT-1 可能在两个空间不同的亚核区室之间以受体特异性方式的分子相互作用中发挥关键作用，从而诱导 AR- 或 GR-AF-1 的强自主反式激活功能。 (C) 2003 Elsevier Ltd. 保留所有权利。
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 speckles 11 shared with GR or estrogen receptor (ER), which colocalize with chiefly activation function-2 (AF-2)-interacting p 160 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. (C) 2003 Elsevier Ltd. All rights reserved.