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C|[sol]|EBP|[alpha]| redirects androgen receptor signaling through a unique bimodal interaction

机译：C | [sol] | EBP |α|通过独特的双峰相互作用重定向雄激素受体信号

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Nuclear expression of CCAAT enhancer binding protein-α (C/EBPα), which supports tissue differentiation through several antiproliferative protein–protein interactions, augurs terminal differentiation of prostate epithelial cells. C/EBPα is also a tumor suppressor, but in many tumors its antiproliferative interactions may be attenuated by de-phosphorylation. C/EBPα acts as a corepressor of the classical androgen response element (ARE)-mediated gene activation by the androgen receptor (AR), but this is paradoxical as the genotropic actions of AR are crucial not only for the growth of the prostate but also for its maintenance and function. We show that DNA-bound C/EPBα recruits AR to activate transcription. C/EBPα-dependent trans-activation by AR also overrode suppression of AREs by C/EBPα elsewhere in a promoter. This mechanism was remarkable in that its androgen dependence was apparently for nuclear translocation of AR; it was otherwise androgen independent, flutamide insensitive and tolerant to disruption of AR dimerization. Gene response profiles and global chromatin associations in situ supported the direct bimodal regulation of AR transcriptional signaling by C/EBPα. This unique mechanism explains the functional coordination between AR and C/EPBα in the prostate and also shows that hormone-refractory AR signaling in prostate cancer could occur through receptor tethering.
机译：CCAAT增强子结合蛋白-α（C /EBPα）的核表达，通过几种抗增殖蛋白-蛋白相互作用来支持组织分化，预示着前列腺上皮细胞的终末分化。 C /EBPα也是一种肿瘤抑制因子，但在许多肿瘤中，其抗增殖相互作用可能会因去磷酸化作用而减弱。 C /EBPα充当由雄激素受体（AR）介导的经典雄激素反应元件（ARE）介导的基因激活的核心抑制剂，但这是自相矛盾的，因为AR的促基因作用不仅对前列腺的生长至关重要，而且对为其维护和功能。我们显示DNA绑定C /EPBα募集AR来激活转录。 AR依赖C /EBPα的反式激活也覆盖了启动子其他位置C /EBPα对ARE的抑制作用。该机制的显着之处在于其雄激素依赖性显然是AR的核易位。否则，它是雄激素非依赖性的，氟他胺不敏感并且耐受AR二聚化的破坏。基因反应概况和全球染色质协会就地支持通过C /EBPα的AR转录信号的直接双峰调节。这种独特的机制解释了AR和C /EPBα在前列腺中的功能协调，还表明前列腺癌中激素难治性AR信号传导可能通过受体束缚发生。

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