Post-transcriptional regulation of androgen receptor mRNA by an ErbB3 binding protein 1 in prostate cancer.
Post-transcriptional regulation of androgen receptor mRNA by an ErbB3 binding protein 1 in prostate cancer.
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DOI：
10.1093/nar/gkq084
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发表时间：
2010-06
影响因子：
14.9
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Zhou H;Mazan-Mamczarz K;Martindale JL;Barker A;Liu Z;Gorospe M;Leedman PJ;Gartenhaus RB;Hamburger AW;Zhang Y
雄激素受体（AR）介导的通路在前列腺癌的发生和进展中发挥着关键作用。然而，人们对 AR mRNA 稳定性和翻译的调节知之甚少，这两个控制 AR 表达的核心过程。 ErbB3 结合蛋白 1 (EBP1) 是一种 AR 辅阻遏物，可负向调节 ErbB3 配体调蛋白 (HRG) 触发的信号传导与 AR 轴之间的串扰，从而影响前列腺癌细胞的生物学特性。 EBP1蛋白表达在临床前列腺癌中也降低。我们之前证明 EBP1 过表达通过影响 AR 启动子活性导致 AR 蛋白水平降低。然而，EBP1 最近被证明是一种 RNA 结合蛋白。因此，我们检查了 EBP1 转录后调节 AR 的能力。在这里，我们表明 EBP1 通过与 AR 3'-UTR 内保守的富含 UC 基序的物理相互作用促进 AR mRNA 衰减。 HRG 处理进一步增强了 EBP1 加速 AR mRNA 衰减的能力。 EBP1 还与 AR mRNA 5' 编码区中由 CAG 形成的茎环结合，并且能够抑制 AR 翻译。因此，前列腺癌中EBP1的减少对于AR转录后上调可能很重要，从而导致AR异常表达和疾病进展。
Androgen receptor (AR)-mediated pathways play a critical role in the development and progression of prostate cancer. However, little is known about the regulation of AR mRNA stability and translation, two central processes that control AR expression. The ErbB3 binding protein 1 (EBP1), an AR corepressor, negatively regulates crosstalk between ErbB3 ligand heregulin (HRG)-triggered signaling and the AR axis, affecting biological properties of prostate cancer cells. EBP1 protein expression is also decreased in clinical prostate cancer. We previously demonstrated that EBP1 overexpression results in decreased AR protein levels by affecting AR promoter activity. However, EBP1 has recently been demonstrated to be an RNA binding protein. We therefore examined the ability of EBP1 to regulate AR post-transcriptionally. Here we show that EBP1 promoted AR mRNA decay through physical interaction with a conserved UC-rich motif within the 3′-UTR of AR. The ability of EBP1 to accelerate AR mRNA decay was further enhanced by HRG treatment. EBP1 also bound to a CAG-formed stem-loop in the 5′ coding region of AR mRNA and was able to inhibit AR translation. Thus, decreases of EBP1 in prostate cancer could be important for the post-transcriptional up-regulation of AR contributing to aberrant AR expression and disease progression.
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前列腺癌的基因表达谱揭示了多个分子途径在转移过程中的参与。
影响因子：
3.8
作者：
Chandran, Uma R.;Ma, Changqing;Dhir, Rajiv;Bisceglia, Michelle;Lyons-Weiler, Maureen;Liang, Wenjing;Michalopoulos, George;Becich, Michael;Monzon, Federico A.
通讯作者：
Monzon, Federico A.
影响因子：
11.2
作者：
Mukhopadhyay NK;Kim J;Cinar B;Ramachandran A;Hager MH;Di Vizio D;Adam RM;Rubin MA;Raychaudhuri P;De Benedetti A;Freeman MR
通讯作者：
Freeman MR
影响因子：
7
作者：
Lehner, B;Sanderson, CM
通讯作者：
Sanderson, CM
影响因子：
16
作者：
Muckenthaler, M;Gray, NK;Hentze, MW
通讯作者：
Hentze, MW
影响因子：
5.3
作者：
Kuwano, Yuki;Kim, Hyeon Ho;Gorospe, Myriam
通讯作者：
Gorospe, Myriam