The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX Netherlands.
Mol Cancer Res. 2010 Jun;8(6):844-54. doi: 10.1158/1541-7786.MCR-09-0424. Epub 2010 May 25.
The androgen receptor (AR) is a member of the nuclear receptor superfamily and is essential for male sexual development and maturation, as well as prostate cancer development. Regulation of AR signaling activity depends on several posttranslational modifications, one of these being ubiquitination. We screened a short hairpin library targeting members of the deubiquitination enzyme family and identified the X-linked deubiquitination enzyme USP26 as a novel regulator of AR signaling. USP26 is a nuclear protein that binds to AR via three important nuclear receptor interaction motifs, and modulates AR ubiquitination, consequently influencing AR activity and stability. Our data suggest that USP26 assembles with AR and other cofactors in subnuclear foci, and serves to counteract hormone-induced AR ubiquitination, thereby contributing to the regulation of AR transcriptional activity.
雄激素受体 (AR) 是核受体超家族的成员，对于男性性发育和成熟以及前列腺癌的发展至关重要。AR 信号转导活性的调节依赖于几种翻译后修饰，其中之一是泛素化。我们筛选了针对去泛素化酶家族成员的短发夹文库，鉴定出 X 连锁去泛素化酶 USP26 是 AR 信号的新型调节剂。USP26 是一种核蛋白，通过三个重要的核受体相互作用基序与 AR 结合，并调节 AR 的泛素化，从而影响 AR 的活性和稳定性。我们的数据表明，USP26 与 AR 和其他辅助因子在亚核焦点中组装，并有助于拮抗激素诱导的 AR 泛素化，从而有助于调节 AR 的转录活性。
