PC-1 works in conjunction with E3 ligase CHIP to regulate androgen receptor stability and activity.
PC-1 works in conjunction with E3 ligase CHIP to regulate androgen receptor stability and activity.
复制标题
PC-1 与 E3 连接酶 CHIP 协同作用，调节雄激素受体的稳定性和活性。
DOI：
10.18632/oncotarget.13230
复制
发表时间：
2016-12-06
期刊：
影响因子：
--
通讯作者：
Li S
中科院分区：
文献类型：
--
作者：
Wang J;Zhang H;Zhang X;Wang P;Wang H;Huang F;Zhou C;Zhou J;Li S
雄激素受体（AR）不仅是一种配体依赖性转录因子，而且也是一种许可因子，是DNA复制的一个组成部分，在有丝分裂过程中被降解。此外，AR活性的失调参与前列腺癌的发生，并导致去势抵抗性前列腺癌（CRPC）。虽然已知AR降解主要通过蛋白酶体介导的途径发生，但对该过程如何调节知之甚少，特别是在M期。PC-1是一种雄激素反应因子，在前列腺癌中表达特异性，在G2/M期表达更高。在这项研究中，PC-1显示与AR和E3连接酶CHIP（Hsc 70相互作用蛋白的羧基末端）相互作用，并增强AR/CHIP相互作用，从而降低AR稳定性。此外，发现PC-1与CHIP一起通过泛素化降低AR，随后的降解主要发生在M期。还发现PC-1抑制雄激素依赖性和雄激素非依赖性前列腺癌细胞中的AR转录活性，并减弱AR的生长抑制。总之，这些研究结果应该提供新的线索，通过PC-1的AR营业额和活动的调制，并揭示了PC-1在AR信号转导的重要作用。
The androgen receptor (AR) is not only a ligand-dependent transcription factor, but also functions as a licensing factor, a component of DNA replication, which is degraded during mitosis. Furthermore, the deregulation of AR activity is involved in the initiation of prostate cancer and contributes to castration resistant prostate cancer (CRPC). While AR degradation is known to occur primarily through a proteasome-mediated pathway, very little is known about how this process is regulated, especially in M phase. PC-1 is an androgen-responsive factor and expresses specificity in prostate cancer, with higher expression noted at G2/M. In this study, PC-1 was shown to interact with AR and E3 ligase CHIP (Carboxy-terminus of Hsc70 Interacting Protein) and to enhance AR/CHIP interactions, thereby decreasing AR stability. Moreover, PC-1 was found to act in conjunction with CHIP in the decreasing of AR via ubiquitination, with the subsequent degradation predominantly occurring during M phase. PC-1 was also found to repress AR transcriptional activity in androgen-dependent and androgen-independent prostate cancer cells and attenuate the growth inhibition of AR. In conclusion, these findings should provide new clues regarding the modulation of AR turnover and activity via PC-1 and reveals an essential role of PC-1 in AR signaling.