激酶对雄激素受体信号传导的调节：对前列腺癌的影响
Kinase modulation of androgen receptor signaling: implications for prostate cancer.
作者信息
Shah Kalpit, Bradbury Neil A
机构信息
Department of Physiology and Biophysics, The Chicago Medical School, Rosalind Franklin University of Medicine & Sciences, North Chicago, IL, 60064, USA.
出版信息
Cancer Cell Microenviron. 2015;2(4). doi: 10.14800/ccm.1023. Epub 2015 Nov 19.
Abstract
Androgens and androgen receptors play essential roles in the development and progression of prostate cancer, a disease that claims roughly 28,000 lives annually. In addition to androgen biding, androgen receptor activity can be regulated via several post-translational modifications such as ubiquitination, acetylation, phosphorylation, methylation & SUMO-ylation. Off these modifications, phosphorylation has been the most extensively studied. Modification by phosphorylation can alter androgen receptor localization, protein stability and transcriptional activity, ultimately leading to changes in the biology of cancer cells and cancer progression. Understanding, role of phosphorylated androgen receptor species holds the key to identifying a potential therapeutic drug target for patients with prostate cancer and castrate resistant prostate cancer. Here, we present a brief review of recently discovered protein kinases phosphorylating AR, focusing on the functional role of phosphorylated androgen receptor species in prostate cancer and castrate resistant prostate cancer.
摘要
雄激素和雄激素受体在前列腺癌的发生和发展过程中起着至关重要的作用，前列腺癌每年约导致28000人死亡。除了雄激素结合外，雄激素受体的活性还可以通过几种翻译后修饰来调节，如泛素化、乙酰化、磷酸化、甲基化和SUMO化。在这些修饰中，磷酸化的研究最为广泛。磷酸化修饰可以改变雄激素受体的定位、蛋白质稳定性和转录活性，最终导致癌细胞生物学特性的改变和癌症进展。了解磷酸化雄激素受体亚型的作用是为前列腺癌和去势抵抗性前列腺癌患者确定潜在治疗药物靶点的关键。在此，我们简要综述了最近发现的使雄激素受体磷酸化的蛋白激酶，重点关注磷酸化雄激素受体亚型在前列腺癌和去势抵抗性前列腺癌中的功能作用。
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