AR
小结
AR是原癌基因，是在与雄激素结合后被激活的核受体。AR蛋白作为类固醇激素激活的转录因子起作用，调节基因转录。在不存在雄激素的情况下，AR主要维持在细胞质中呈无活性构象；在雄激素结合后，AR构象变化被激活，允许其易位进入细胞核，同源二聚化并在雄激素响应元件（ARE）基序的位点处与DNA结合。AR与辅助辅激活因子和辅阻遏物合作一起用于激活或抑制AR介导的靶基因的转录。 AR功能丧失的胚系突变导致遗传性XY雄性和啮齿动物发育为外部雌性表型，缺乏内部性器官。 AR信号传导在前列腺癌中特别是在去势抵抗性前列腺癌（CRPC）中是相当重要的。但在CRPC中AR经常改变并导致持续激活尽管CRPC的雄激素水平丧失。 AR基因的突变可导致CRPC中抗雄激素治疗的临床抗性。
AR (androgen receptor) is a nuclear receptor that is activated following binding of androgenic hormones. The AR protein acts as a steroid-hormone activated transcription factor that regulates gene transcription. In the absence of androgen, AR is predominantly maintained in an inactive conformation in the cytoplasm. Upon androgen binding, AR undergoes an activating conformational change that allows for its translocation into the nucleus, homodimerization and binding to DNA at sites with androgen response elements (ARE) motifs. In concert with accessory coactivators and corepressors, AR serves to activate or repress the transcription of AR-mediated target genes. Germline loss-of-function mutations in AR cause genetic XY males and rodents to develop as external phenotypic females, also lacking internal sexual secondary organs. AR signaling is important in prostate cancers, particularly in tumors that become resistant to androgen deprivation therapies, termed castration-resistant prostate cancers (CRPC). AR is frequently altered in CRPCs resulting in continued activation despite a castrate level of androgen. Mutations in AR can lead to clinical resistance to antiandrogen therapy in CRPC.